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Mononeuritis Multiplex

Mononeuritis multiplex is a disease of the nervous system that affects two random body areas with severe pain and damage to motor, and sensory function. It most commonly occurs due to disruption of blood supply to the peripheral nervous system, although various etiologies are thought to underlie the disease. Affected areas depend on the causative etiologies.


History is critical in determining the underlying causative factors responsible for the disease. Associated pain is of aching quality and is felt deep in the body. It starts in areas of the low back and then radiates unilaterally to the knee and the thigh. Lancinating pain may occur, particularly at night. Patients with diabetes mellitus generally present in a different manner. They report an acute episode of severe pain in the thigh on one side only. This is usually followed by wasting of the muscles of the anterior thigh and associated weakness.

In addition to pain, patients frequently complain of several symptoms of neurological nature such as tingling, dysesthesia (pain of burning quality), numbness, paresthesias (abnormal sensations) and sometimes frank paralysis.

On physical exam, deep tendon reflexes are generally preserved and accompanied by excellent muscle strength, with the exception of localized regions where the damage is more severe. Other findings on the physical exam may point to the involvement of the following nerve structures: femoral nerve, axillary nerve, radial nerve, median nerve, ulnar nerve, sciatic nerve, common peroneal nerve, peroneal nerve and sciatic nerve. The latter is most frequently affected [3]. In addition, mononeuritis multiplex is linked with autonomic dysfunction.

Generalized Lymphadenopathy
  • Chest and abdominal computed tomography showed generalized lymphadenopathy.[ncbi.nlm.nih.gov]
Leg Edema
  • We regard inflammatory plaques and leg edema with elevated serum CRP as an indication of a more severe condition, and treated them effectively with prednisolone.[ncbi.nlm.nih.gov]
Epigastric Pain
  • A 31-year-old woman was admitted with a complaint of epigastric pain. She had a history of bronchial asthma. One week before admission, white blood cell count was 20,800/mm3 with 59% eosinophils.[ncbi.nlm.nih.gov]
Cutaneous Manifestation
  • This case illustrates the difficulties in differentiating dysesthesia accompanying cutaneous manifestations of exanthem from neurologic disease on the basis of the clinical appearance alone.[ncbi.nlm.nih.gov]
  • Prospective, randomized trials of interferon-a in patients with type II mixed cryoglobulinemia and hepatitis C infection found improvement in the cutaneous manifestations of the disease and a reduction in the level of circulating cryoglobulins, serum[bcm.edu]
Foot Drop
  • This report describes a 71-year-old man with biopsy-proved giant cell arteritis, mononeuritis (foot drop) multiplex, and high-titer complement-activating rheumatoid factor without rheumatoid arthritis. Possible pathogenic relationships are discussed.[ncbi.nlm.nih.gov]
  • She underwent carpal tunnel decompression surgery with initial diagnosis of acute carpal tunnel syndrome but failed to respond to the surgery, and two month later, she presented with foot drop.[ncbi.nlm.nih.gov]
  • For example, sudden loss of the ability to lift the foot normally while walking (foot drop) can be caused by mononeuritis multiplex, when it is accompanied by loss of nerve function elsewhere in the body.[medicinenet.com]
  • Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly[books.google.com]
  • PATIENT A 63-year-old woman with a history of acute myeloid leukemia in hematologic remission experienced a succession of acute clinical neuropathies (left median, right radial, and left sciatica) several months before hematologic relapse of leukemia…[semanticscholar.org]
  • A 63-year-old woman with a history of acute myeloid leukemia in hematologic remission experienced a succession of acute clinical neuropathies (left median, right radial, and left sciatica) several months before hematologic relapse of leukemia.[ncbi.nlm.nih.gov]
  • Materials and Methods We present a rare case of a 71-year-old man with IE in whom mononeuritis multiplex was revealed on electromyography; further, he presented with lower back pain and sciatica.[synapse.koreamed.org]
  • Non-narcotic Pain Study Protocol Recruiting NCT01974609 Phase 4 Narcotic;non-narcotic 15 NSAIDs in Sciatica NSAIDS IN SCIATICA Recruiting NCT03347929 Phase 4 Naproxen 500 Mg;Placebo 16 Ultrasound-guided Caudal or Interlaminar Corticosteroid Epidural Injection[malacards.org]
  • That for the most part is GONE (or has morphed into nerve entrapments) And most recently I was dx’d with reactive arthritis that causes nerve related symptoms like recurring sacroillitis and sciatica. Ok-I’ve posted blogs about nerves before.[butudontlooksick.wordpress.com]
Limb Weakness
  • Be Misdiagnosed as Carpal Tunnel Syndrome. ( 27362698 ) 2016 17 Steroid Responsive Mononeuritis Multiplex in the Cronkhite-Canada Syndrome. ( 27899913 ) 2016 18 Diffuse toxic goiter and coexisting hurthle cell carcinoma of thyroid presenting as lower limb[malacards.org]
  • 27362698 ) Ghazaei F....Raissi G.R. 2016 17 Steroid Responsive Mononeuritis Multiplex in the Cronkhite-Canada Syndrome. ( 27899913 ) Lo Y.L....Mesenas S. 2016 18 Diffuse toxic goiter and coexisting hurthle cell carcinoma of thyroid presenting as lower limb[malacards.org]
  • References: [27] [9] [28] [29] Differential diagnoses Mononeuritis multiplex ( multiple mononeuropathy ) Radicular neuropath y (associated with acute onset of severe back pain that radiates to the legs and arms) Amyotrophic lateral scler osis ( asymmetric limb[amboss.com]
  • Abstract Although typhoid fever can frequently lead to such neurological manifestations as confusion, delirium, and encephalopathy, Guillain-Barré syndrome, aphasia and mononeuritis multiplex occur very rarely.[ncbi.nlm.nih.gov]


History, physical exam and overall clinical picture are critical in suggesting the presence of the disease. Laboratory tests are subsequently performed to determine the underlying etiologic cause. It is not necessary to perform imaging tests to establish the diagnosis.

Workup generally includes a complete blood count, c-reactive protein levels and erythrocyte sedimentation rate (ESR) to assess any possible systemic inflammatory disease, parvovirus B-19 serology, Borrelia burgdorferi serology when suspicion in Lyme disease is high, human immunodeficiency virus (HIV) serology in patients at risk, hepatitis serology, herpes viral serology and an autoimmune profile.

Some conditions that can result in mononeuritis multiplex can only be diagnosed with a nerve biopsy. Histopathological analysis will show infiltration of inflammatory cells within the perivascular compartment, damage to axonal structures, presence of multinucleated giant inflammatory cells and axonal loss [10]. Mononeuritis multiplex that is particularly associated with HIV manifests with necrotizing vasculitis in epineural arteries.

Leptospira Interrogans
  • Leptospirosis is a zoonosis caused by the spirochete, Leptospira interrogans. While most cases of leptospirosis are mild to moderate, the course may be complicated by multiorgan dysfunction.[ncbi.nlm.nih.gov]
Coxiella Burnetii
  • Serologic studies identified Coxiella burnetii as the cause of the febrile disease (Q fever). Fourteen days doxycycline treatment (200 mg daily) induced rapid and complete recovery.[ncbi.nlm.nih.gov]
  • A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir.[ncbi.nlm.nih.gov]


Treatment commences after the specific etiology underlying mononeuritis multiplex is diagnosed. Options considerably vary depending on the disease. Vasculitis, in particular, needs to be promptly treated to avoid serious complications that can lead to death [11] [12]. The aim of the treatment, aside from resolving the original condition that led to the development of the symptoms, is to provide supportive care for sufficient independent functioning and make sure symptoms are controlled. For example, in diabetes mellitus, it is necessary to keep blood sugar levels under close observation.

Supportive treatment can be administered in various forms. Most commonly, it consists of vocational and occupational therapy, in addition to providing devices that may help the patient in achieving mobility such as braces, splints, and wheelchairs. Physical therapy in the form of physical exercises can also improve overall muscular strength.

Overall safety management is also critical, as patients are more prone to falls and injuries due to the damage of motor and sensory function. Some safety measures that need to be followed are the following: use of railing whenever they are present, good lighting to avoid unnecessary accidents and adequate testing of the temperature of water before showering. It is also necessary to remove unnecessary physical obstacles such as loose rugs and to avoid wearing shoes with open toes or high heels.

Some patients may suffer from damage to sensations. In these cases, it is very important to regularly monitor the development of injuries or bruises, especially in the feet or areas affected by the disease. Without adequate examination, the areas may become infected without the awareness of the patient, because of deficient pain sensation.

On the other hand, some areas are particularly prone to damage due to excessive pressure such as the elbows and the knees. It is critical for the patient to avoid putting pressure on sensitive areas. Patients should be advised not to cross their legs as this increases pressure over the knees or lean on their elbows.

Pharmacotherapy plays an important part in the management of the disease. Lancinating pain may be treated with several anticonvulsants such as phenytoin, carbamazepine, pregabalin, and gabapentin. Antidepressants can also decrease pain, especially amitriptyline, duloxetine, and nortriptyline. Pharmacotherapy is not restricted to prescription drugs. Over the counter medications can be useful, particularly acetaminophen and non-steroidal anti-inflammatory agents such ibuprofen. Nonetheless, medications should be kept to a minimum in order to decrease side effects.

Patients are advised to improve their positioning to remove pressure over any area with damaged nerves. This helps in reducing pain. Unfortunately, autonomic dysfunction does not respond well to treatment.


Mononeuritis multiplex can completely resolve when the disease is diagnosed and treated promptly, although multiple recurrences can occur. Nonetheless, patients should expect months or sometimes years for resolution of their symptoms.

Overall morbidity depends on many factors and may range from absence of any disability to severe dysfunction. Mononeuritis multiplex can also be accompanied by a number of complications in the form of muscular atrophy, deformity of anatomical structures, recurrent injuries that the patient may not be aware of, organ dysfunction (particularly organs under autonomic control such as the heart, bladder and stomach), and psychological damage which can result in reduced confidence and social interaction. The latter can also occur because of excessive pain and motor dysfunction. Finally, impotence may develop in male patients.


Mononeuritis multiplex results from damage to the axons, and ultimately resulting in deficits in the transmission of the electrical messages between nerve cells. Oxygen deficiency because of a decrease in blood flow as well as damage to the walls of blood vessels subsequent to inflammation are responsible for the development of the condition and target especially small arteries within the nerve structures.

Mononeuritis multiplex is associated with various processes and conditions. Infections are particularly important in the etiology of the disease. Several infectious disorders are known to be involved and they include hepatitis B and C, acute infection with hepatitis A, infections with herpes simplex virus, HIV infections with or without AIDS, Lyme disease, leprosy and acute infection with parvovirus B-19 [2]. Rheumatological diseases also play a prominent role in the pathology of the disease. Known associated rheumatological conditions are scleroderma, Sjogren syndrome, Wegener granulomatosis, Behcet disease, Henoch-Schönlein purpura, giant cell arteritis, rheumatoid arthritis, polyarteritis nodosa and systemic lupus erythematosus [3].

Other conditions that may be associated with mononeuritis multiplex are diabetes mellitus, neurosarcoidosis, amyloidosis, small cell lung cancer, graft versus host disease, tumor invasion of nerve structures (especially with B-cell leukemia, carcinoid tumor and lymphomas), cryoglobulinemia, hypereosinophilia, Churg-Strauss syndrome, idiopathic thrombocytopenic purpura, atopy-related peripheral neuritis, amphetamine angiitis and gasoline sniffing [4].

Patients with mononeuritis multiplex are usually susceptible to multiple recurrences, with worsening progression over time. Around 33% of all cases have unknown etiology [5].


Mononeuritis multiplex is a rare disorder, although overall incidence and prevalence remain unknown. The most common causes of mononeuritis multiplex involve damage to blood vessels supplying neural structures, with the aged being the most affected. The mean age of onset of vasculitic neuropathy is between 51 and 67 years [6].

Reported prevalence in conjunction with the most important causative factors is the following [7]: 60% in polyarteritis nodosa, 8% in untreated hepatitis C (although this is likely to be over-estimated), 8% in Sjogren's syndrome, 40 to 50% in rheumatoid arthritis vasculitis, 5% to 20% in rheumatoid arthritis, 13% in Wegener's granulomatosis, 25% in Churg-Strauss syndrome, 65% in vasculitic neuropathies, 1% in systemic lupus erythematosus (SLE), 9% in patients with SLE but with evidence of vasculitis and a small association with Henoch Schönlein Purpura and temporal arteritis.

Sex distribution
Age distribution


The pathophysiological processes underlying mononeuritis multiplex remain unknown. It is thought, however, that activated white blood cells and endothelial cells are central to the pathogenesis of the disease, in addition to the altered function of adhesion molecules. The common form of mononeuritis multiplex involves necrosis and inflammation of the small arteries supplying the nerve fibers. This eventually leads to random areas of ischemia. In addition, inflammation involving the full thickness of the vessel well in combination with fibrinoid necrosis can cause ischemia and injury to the nerve cells [8].

Other disease processes may also result in the development of the condition. They include the formation of immune complexes, especially in the context of polyarteritis nodosa and essential mixed cryoglobulinemia. This mechanism is also thought to be involved in polyarteritis nodosa associated with hepatitis B and cryoglobulinemia related to hepatitis C infection [9]. Furthermore, an exaggerated immune response may result from hapten formations. This mechanism is thought to play a particularly important role in vasculitis resulting from drug hypersensitivity. Finally, ANCA (antineutrophil cytoplasmic antibodies) production and exaggerated activation of T lymphocytes are thought to mediate the vasculitis in Wegener's granulomatosis and Churg-Strauss syndrome. ANCA are also likely to mediate damage in microscopic polyarteritis [9].


There are no preventive measures that can be used for mononeuritis multiplex.


Mononeuritis multiplex presents with a constellation of symptoms that mostly target the peripheral nervous system. It results from a large array of medical conditions that ultimately affect the functioning of the nerves. The most common cause is a disruption of the vascular blood supply to the peripheral nerve structures, with the development of random areas of necrosis along the nerve fiber. Diabetes is one of the main culprits, in addition to infections, vasculitis and other rheumatological diseases [1]. Patients commonly present with severe episodes of localized and acute pain, with lancination. There may also be associated motor dysfunction, with weakness and atrophy. Workup is aimed at elucidating the cause and mostly consists of an array of laboratory tests. Imaging is not necessary to diagnose the disease, but in some cases, biopsy and pathological analysis are required. Treatment is aimed at controlling symptoms and resolving the underlying condition. Pharmacotherapy is particularly important in controlling the pain. Furthermore, patients also require social and psychological support. Prognosis varies considerably depending on the underlying etiology. Most patients can expect to recover, although multiple recurrences are very common.

Patient Information

Mononeuritis multiplex is a medical condition that manifests with damage to nerve structures in the body. Several underlying diseases can lead to the development of the condition, although deficient blood supply to peripheral nerve structure is the most common cause. This usually results from high levels of sugars in the blood, in addition to many infectious and inflammatory diseases. Patients usually present with sharp or deep pain occurring in sudden episodes, and may be associated with muscular weakness localized to particular muscles in the human body. Workup is aimed at elucidating underlying causes and generally consists of a broad range of blood tests. Imaging is not useful for diagnosing the disease, but sometimes the physician may take a sample of tissue for pathological analysis. This may reveal the cause in select conditions. Treatment is broad and is directed at the presenting symptoms, in addition to underlying causes. Patients can benefit from a range of medications that can help them with their pain. Most patient will do well, although outcomes vary a lot, depending on the disease.



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  2. Elamin M, Alderazi Y, Mullins G, et al. Perineuritis in acute lyme neuroborreliosis. Muscle Nerve. 2009 Jun; 39(6):851-4.
  3. Koo J. The psychosocial impact of acne: patient's perceptions. J Am Acad Dermatol. 1995; 32:S26-S30.
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  5. Mauermann ML, Ryan ML, Moon JS, et al. Case of mononeuritis multiplex onset with rituximab therapy for Waldenstrom's macroglobulinemia. J Neurol Sci. 2007 Sep 15; 260(1-2):240-3.
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  9. Wilkins JW, Voorhees JJ. Prevalence of nodulocystic acne in white and Negro males. Arch Dermatol. 1970; 102:631-634.
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  11. Gorson KC. Vasculitic neuropathies: an update. Neurologist. 2007 Jan; 13(1):12-9.
  12. Garzoni L, Vanoni F, Rizzi M, et al. Nervous system dysfunction in Henoch-Schonlein syndrome: systematic review of the literature. Rheumatology (Oxford). 2009 Dec; 48(12):1524-9.

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Last updated: 2019-07-11 20:51