Mononeuropathy Multiplex

MP Collins, Medical College of Wisconsin, Milwaukee, WI, USA

r 2014 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by Richard K Olney, volume 3, p 201, r 2003, Elsevier Inc.

The term ‘mononeuropathy multiplex’ refers to an anatomical Table 1 Differential diagnosis of multifocal/asymmetric
neuropathy
pattern of peripheral neuropathy in which the pathological
process affects individual nerves focally or multifocally rather A. Ischemic neuropathies
than many nerves diffusely, contrasting with a more generally 1. Peripheral nerve vasculitis
acting polyneuropathy. Single nerve lesions are mono- 2. Livedoid vasculopathy
neuropathies. Disorders involving two or more nerves are 3. Sickle cell anemia
multiple mononeuropathies, a designation synonymous with 4. Cholesterol emboli syndrome
mononeuropathy multiplex or multifocal neuropathy. Use of 5. Atrial myxoma
the label mononeuritis multiplex should be discouraged, as 6. Thrombophilic states (diffuse intravascular coagulation, essential
thrombocythemia, antiphospholipid antibody syndrome)
not all multiple mononeuropathies are inflammatory in ori-
gin. In early multiple mononeuropathies, the condition can be B. Inflammatory/immune-mediated neuropathies
clearly identified as such by signs/symptom of individual 1. Sarcoidosisa
nerve involvement, but with disease progression, contiguous 2. Multifocal acquired demyelinating sensory and motor neuropathy
3. Multifocal motor neuropathy
nerves are affected, producing a so-called overlapping or
4. Multifocal acquired motor axonopathy
confluent multiple mononeuropathy. If not too far advanced,
5. Multifocal variants of Guillain–Barré syndrome
the multifocal nature of the neuropathy can still be discerned 6. Neuralgic amyotrophya
by accentuated involvement of single nerves within one limb. 7. Neuropathy with eosinophilic disordersa
In patients with longstanding disease, the neuropathy may 8. Neuropathy with gastrointestinal conditions (Chron’s disease,
mimic a generalized polyneuropathy but for the presence of ulcerative colitis, celiac sprue)a
asymmetries, then warranting the label asymmetrical poly- 9. Chronic graft vs. host disease
neuropathy. Of course, many generally acting peripheral ner- 10. Wartenberg migrant sensory neuritis (inflammatory cases)a
vous system (PNS) disorders also produce an asymmetrical 11. Disialosyl antibody-related neuropathy
pattern (e.g., Charcot–Marie–Tooth neuropathies). Therefore, 12. Sensory perineuritis
13. Hashimoto thyroiditis
an asymmetrical polyneuropathy is less specific for a multi-
14. Multiple sclerosis with multifocal demyelinating neuropathy
focal process than a true multiple mononeuropathy. Although
some causes for a multifocal neuropathy, such as the vasculi- C. Infectious/toxic neuropathiesa
tides, are occasionally reported to present as a symmetrical 1. Leprosy
polyneuropathy, detailed history and examination almost al- 2. Lyme disease
3. Viral (human immunodeficiency virus, human T-cell lymphotropic
ways reveal focal or asymmetrical elements to the neuropathy.
virus type I, varicella zoster virus, cytomegalovirus, Epstein–Barr
The literature is replete with references to ‘mononeuritis
virus, parvovirus B19, West Nile virus, measles)
multiplex’ in patients having an overlapping asymmetric 4. Other (infective endocarditis, tuberculosis, sporotrichosis,
pattern. meningococcus, group A b-hemolytic streptococcus,
The best understood pathogenic mechanisms under- leptospirosis, hepatitis A, Mycoplasma pneumoniae Salmonella
lying multiple mononeuropathies are multifocal ischemia, typhi Pseudomonas aeruginosa, trichinosis, ascaris, Plasmodium
multifocal inflammatory demyelination, other focally acting falciparum, scrub typhus, Coxiella burnetii, relapsing fever)
inflammatory processes, PNS infections, multiple nerve entra- D. Drug-induced neuropathiesa
pments, other types of compressive nerve lesions, traumatic 1. Antibiotics (penicillin, sulfonamides, minocycline)
injuries to peripheral nerves, burns, distributed PNS tumors, 2. Tumor necrosis factor-a inhibitors
neoplastic cell infiltration, multifocal deposition of toxic 3. Montelukast and other leukotriene receptor antagonists
proteins, and intraneural hemorrhages. A multiple mono- 4. Interferon-a
neuropathy is often attributed to vasculitis, but there are many 5. Drugs of abuse (amphetamines, cocaine, heroin)
other etiologies for this phenotype, as detailed in Table 1. 6. Other (cromolyn, thiouracil, allopurinol, naproxen, valacyclovir,
leflunomide, gasoline sniffing)
For this reason, diagnostic tests designed to identify non-
vasculitic diseases are usually required in any patient with a E. Genetic neuropathies
progressive multifocal neuropathy, with the possible exception 1. Hereditary neuropathy with liability to pressure palsies
of a preexisting, pathologically established diagnosis of sys- 2. Hereditary neuralgic amyotrophy
3. Porphyria
temic vasculitis. Electrodiagnostic studies are crucial for con-
4. Familial amyloid polyneuropathy (tranthyretin)
firming the presence of an asymmetrical/multifocal process
5. Tangier disease
and directing attention to the uncommon demyelinating 6. Krabbe’s disease
causes for this profile, for example, Lewis–Sumner syndrome, 7. Mitochondrial disorders
multifocal motor neuropathy, hereditary neuropathy with li-
ability to pressure palsies (HNPP), and the leukodystrophies. (Continued )

94 Encyclopedia of the Neurological Sciences, Volume 3 doi:10.1016/B978-0-12-385157-4.00667-9


Table 1 Continued
F. Mechanical neuropathies
1. Multiple peripheral nerve injuries
2. Multifocal entrapments
3. Postoperative neuropathies
4. Compartment syndromes
5. Burns
6. Wartenberg’s migrant sensory neuritis (mechanical cases)
G. Neuropathies related to neoplastic diseases
1. Direct infiltration of nerves by tumor
2. Paraneoplastic (vasculitic and nonvasculitic)a
3. Multifocal peripheral nerve tumors with external/internal
compression
4. Neurofibromatosis type 2 (Schwann cell proliferation/dysfunction)
5. Lymphomatoid granulomatosisa
6. Neoplastic meningitis
7. Primary systemic immunoglobulin light chain (AL) amyloidosis
8. Nonamyloid light chain or immunoglobulin M (IgM) deposition
a. Waldenström’s macroglobulinemia
b. IgM monoclonal gammopathy of undetermined significance
H. Intraneural hemorrhage
1. Idiopathic thrombocytopenic purpura
2. Acute leukemia
3. Hemophilia
a Dyck PJ, Norell JE, and Dyck PJ (1999) Microvasculitis and ischemia in diabetic
Conditions occasionally or routinely associated with vasculitis.
An unexplained, progressive multiple mononeuropathy is
also an indication for nerve biopsy. Nerve biopsy has the
potential to elucidate such etiologies as vasculitis, leprosy,
sarcoidosis, noninflammatory thrombosis, cholesterol emboli,
eosinophilic syndromes, sensory perineuritis, cytomegalovirus
infection, diffuse infiltrative lymphocytosis syndrome, amy-
loidosis, neoplastic cell infiltration, intraneural hemorrhage,
and PNS tumors. Biopsy can reveal suggestive but non-
pathognomonic findings in cases of multifocal inflammatory
demyelination, HNPP, and Tangier disease. Of course, history
may obviate the need for extensive testing in patients
with physical trauma, common entrapment neuropathies,
Mononeuropathy Multiplex 95
or other compressive mechanisms. As a rule, multifocal neu-
ropathies are more likely than generalized ones to ensue from
treatable diseases, mandating close scrutiny for this ana-
tomical pattern in any patient presenting with a peripheral
neuropathy.
See also: Brachial Plexopathies. Chronic Inflammatory
Demyelinating Polyradiculoneuropathy (CIDP). Multifocal Motor
Neuropathy. Neuropathies, Diabetic. Neuropathies, Entrapment.
Neuropathies, Overview. Vasculitic Neuropathy
Further Reading
Burns TM, Dyck PJ, Aksamit AJ, and Dyck PJ (2006) The natural history and long-
term outcome of 57 limb sarcoidosis neuropathy cases. Journal of Neurological
Sciences 244: 77–87.
Cats EA, van der Pol WL, Piepers S, et al. (2010) Correlates of outcome and
response to IVIg in 88 patients with multifocal motor neuropathy. Neurology 75:
818–825.
Collins MP, Dyck PJ, Gronseth GS, et al. (2010) Peripheral Nerve Society guideline
on the classification, diagnosis, investigation, and immunosuppressive therapy
of non-systemic vasculitic neuropathy: Executive summary. Journal of the
Peripheral Nervous System 15: 176–184.
lumbosacral radiculoplexus neuropathy. Neurology 53: 2113–2121.
Halperin JJ (2003) Lyme disease and the peripheral nervous system. Muscle &
Nerve 28: 133–143.
Kelly JJ and Karcher DS (2005) Lymphoma and peripheral neuropathy: A clinical
review. Muscle & Nerve 31: 301–313.
Ooi WW and Srinivasan J (2004) Leprosy and the peripheral nervous system: Basic
and clinical concepts. Muscle & Nerve 30: 393–409.
Roullet E, Assuerus V, Gozlan J, et al. (1994) Cytomegalovirus multifocal
neuropathy in AIDS: Analysis of 15 consecutive cases. Neurology 44:
2174–2182.
Stork AC, van der Meulen MF, van der Pol WL, et al. (2010) Wartenberg migrant
sensory neuritis: A prospective follow-up study. Journal of Neurology 257:
1344–1348.
Van Alfen N and van Engelen BG (2006) The clinical spectrum of neuralgic
amyotrophy in 246 cases. Brain 129: 438–450.
Viala K, Renié L, Maisonobe T, et al. (2004) Follow-up study and response to
treatment in 23 patients with Lewis–Sumner syndrome. Brain 127: 2010–2017.