Mononeuritis multiplex

Mononeuritis multiplex

Mononeuritis multiplex is a group of disorders that involves inflammation of two or more nerves. Mononeuritis multiplex is characterized by 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. Mononeuritis multiplex syndromes can be distributed bilaterally, distally, and proximally throughout the body.

Typically, mononeuritis multiplex is associated with but not limited to systemic disorders such as the following 1):

  • Diabetes mellitus 2)
  • Vasculitis 3)
  • Amyloidosis 4)
  • Direct tumor involvement – Lymphoma, leukemia 5)
  • Polyarteritis nodosa 6)
  • Rheumatoid arthritis 7)
  • Systemic lupus erythematosus 8)
  • Paraneoplastic syndromes 9)

Mononeuritis multiplex causes

Mononeuritis multiplex can be associated with several disorders including infectious, inflammatory, neoplastic, toxic, metabolic and hereditary conditions.

Mononeuritis multiplex can be associated with the following infections:

  • Lyme disease 10)
  • Leprosy – An Indian study, by Jaiswal et al 11), 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
  • Acute viral hepatitis A 12)
  • Hepatitis B 13)
  • Hepatitis C 14)
  • Acute parvovirus B-19 infection 15)
  • Herpes simplex virus infection 16)
  • AIDS and HIV infection 17)

Mononeuritis multiplex can be associated with the following rheumatologic disorders:

  • Granulomatosis with polyangiitis (previously called Wegener granulomatosis) 18)
  • Henoch-Schönlein syndrome 19)
  • Sjögren syndrome 20)
  • Behçet’s disease 21)
  • Temporal (giant cell) arteritis 22)
  • Systemic lupus erythematosus 23)
  • Rheumatoid arthritis 24)
  • 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 25)
  • Scleroderma 26)

Mononeuritis multiplex can be associated with the following chronic conditions:

  • Diabetes mellitus 27)
  • Amyloidosis 28)
  • Neurosarcoidosis 29)
  • Celiac disease 30)

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

  • Chronic graft versus host disease (GVHD) 31)
  • Direct tumor invasion with intraneural spread – Lymphoma 32), B-cell leukemia 33), carcinoid tumor 34)
  • Paraneoplastic – Small cell lung cancer 35)

Mononeuritis multiplex can be associated with the following hematologic conditions:

  • Churg-Strauss syndrome 36)
  • Hypereosinophilia
  • Cryoglobulinemia 37) – 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 38)
  • Hypereosinophilia 39)
  • Atopy-related peripheral neuritis (see below) 40)
  • Idiopathic thrombocytopenic purpura 41)

Mononeuritis multiplex can be associated with the following miscellaneous conditions:

  • Amphetamine angiitis 42)
  • Gasoline sniffing 43)

In addition, mononeuritis multiplex can be associated with the genetic disorder Tangier disease 44) and with multiple compression neuropathies.

Moreover, in a study of 157 patients with eosinophilic granulomatosis with polyangiitis, Cottin et al 45) found mononeuritis multiplex to be associated with cases that included systemic vasculitis and the presence of antineutrophil cytoplasmic antibodies.

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 46).

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 47).

Mononeuritis multiplex symptoms

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. Individuals with diabetes typically present with acute onset of severe, unilateral 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

Loss of sensation and movement may be associated with dysfunction of specific nerves. Examination reveals preservation of reflexes and good strength except in regions that have been more profoundly affected. Some common findings of mononeuritis multiplex are as follows (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
  • Peroneal nerve palsy
  • Autonomic dysfunction – Dysfunction in the part of the nervous system that controls involuntary bodily functions, such as the glands, blood vessels, and heart

Mononeuritis multiplex diagnosis

The suspected cause of mononeuritis multiplex, as suggested by the patient’s history, symptoms, and pattern of symptom development, helps to determine which tests to perform. Laboratory tests ordered 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
  • Herpes viridae serology
  • Parvovirus B-19 antibodies

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

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) 48). 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. A pattern of necrotizing vasculitis of epineural arteries may be observed in HIV-related mononeuritis.

Some studies have indicated that combining a nerve biopsy with a muscle biopsy can help clinicians to better diagnose peripheral nerve vasculitis, because it appears that in many cases, individuals with peripheral nerve vasculitis also have vasculitis in striated muscle 49). A 1988 study, for example, found that among patients known to have peripheral nerve vasculitis, up to 45% of them did not have demonstrable evidence of the condition in their superficial peroneal nerve but did show evidence of vasculitis in their peroneus brevis muscle 50).

However, a 2008 study of patients with proven peripheral nerve vasculitis (most of whom presented with either asymmetrical axonal polyneuropathy or mononeuritis multiplex) found that the benefits of combining nerve and muscle biopsies for the diagnosis of peripheral nerve vasculitis seem to depend on which muscle and nerve are chosen 51). When compared with results from sural nerve biopsies alone, the report’s authors found no significant increase in diagnoses of peripheral nerve vasculitis derived from combined biopsies of the sural nerve and the vastus lateralis muscle.

Sensory nerve conduction studies

Sensory nerve conduction studies show abnormalities of decreased amplitude in the presence of axonal disruption. Physical examination and history will direct the electromyographic examination. Sensory nerve conduction studies 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 in mononeuritis multiplex. However, the H-reflex is typically performed only in the tibial nerves, limiting its usefulness in investigating mononeuritis multiplex.

Motor nerve conduction studies

Abnormalities are similar to those seen in axonal polyneuropathies, with the exception of the anatomic distribution. A reduction in the 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. 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

Findings on the needle electrode examination can vary, depending on the severity and time course of the disorder. Findings are typically neuropathic and may include abnormal spontaneous membrane activity (positive sharp waves and fibrillation potentials) and, during and after reinnervation, increases in motor unit action potential (MUAP) duration, amplitude, and polyphasia. Additionally, the loss of motor axons should generate a reduced number of motor unit action potentials firing at high rates (ie, reduced recruitment).

Mononeuritis multiplex treatment

Consultations in the treatment of mononeuritis multiplex can include the following:

  • 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
  • Pain management specialist and physiatrist referrals may be needed in selected cases

The physician must try to elucidate the underlying cause and initiate appropriate treatment according to the established protocols for the specific disease condition. Disorders such as vasculitis 52) can be fatal if not treated. A study by de Luna et al 53) of plasma exchange in the treatment of systemic necrotizing vasculitides found that in patients with mononeuritis multiplex, improvement in severe motor weakness occurred.

In addition, 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.

Other treatment considerations include the following:

  • 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. These may include, but are not necessarily limited to, installation of railings, removal of obstacles (eg, loose rugs that may slip on the floor), installation of low-level lighting, and testing of water temperatures before bathing.

Follow-up

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

Mononeuritis multiplex prognosis

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 54) 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.

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