Neuropathies associated with cytomegalovirus infection …

Peripheral Neuropathies

Updated 11.16.2024
Released 01.05.1995
Expires For CME 11.16.2027

Neuropathies associated with cytomegalovirus infection

Authors: Niranjan N Singh MD, Florian P Thomas MD MA PhD MS

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Editor: Louis H Weimer MD

Neuropathies associated with cytomegalovirus infection

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Introduction

Overview

Cytomegalovirus is the most common cause of polyradiculopathy in AIDS. It occurs in about 2% of HIV-infected patients referred to neurologists. Expeditious diagnosis is crucial, as this disease may progress rapidly to death, but does respond to antiviral therapy when started early. The authors provide an overview of neuropathies associated with cytomegalovirus infection.

Historical note and terminology

Prior to the AIDS epidemic, cytomegalovirus was rarely associated with peripheral neuropathies, but was recognized as an antecedent infection associated with Guillain-Barré syndrome (27; 10). Since the first AIDS cases were identified in the United States in 1981, several discrete neuropathic syndromes have been linked to cytomegalovirus, including lumbar radiculopathy, distal symmetrical polyneuropathy, mononeuritis multiplex (Behar and McCutchan 1987; 38; 13), and gastroparesis (54). Cytomegalovirus is one of the primary opportunistic pathogens in late stages of AIDS and affects multiple organs (40). Retinitis is the most common manifestation, affecting 10% to 20% of patients, but esophagitis, gastritis, colitis, pneumonitis, myelitis, encephalitis, and optic neuropathy also occur. Physicians should have a low threshold for entertaining this diagnosis, as many patients improve significantly with antiviral treatment.

Clinical manifestations

Presentation and course

Peripheral neuropathy is the most common neurologic complication HIV seropositive individuals. Clinical and neurophysiological evaluations reveal evidence of neuropathy in most AIDS patients (04; 49; Gastaut et all 1989; 22). In terminal AIDS pathological evidence of neuropathy is present essentially in all patients (36; 44). HIV-associated neuropathy presents as several different subtypes: (a) distal sensory polyneuropathy, (b) acute and chronic inflammatory neuropathies, (c) polyradiculopathy, (d) mononeuritis multiplex, (e) autonomic neuropathy, and (f) diffuse infiltrative lymphocytosis syndrome (56). Among AIDS patients, cytomegalovirus is associated with polyradiculopathy, mononeuritis multiplex, painful distal symmetrical polyneuropathy, and myelitis.

Cytomegalovirus is the most common cause of polyradiculopathy in AIDS (08). It occurs in about 2% of HIV infected patients referred to neurologists. Expeditious diagnosis is crucial, as this disease may be rapidly progressive, but does respond to antiviral therapy when started early.

AIDS-associated polyradiculopathy usually occurs when CD4 counts drop below 40, in the presence of other AIDS defining illnesses, and in association with cytomegalovirus, or other end-organ infection (56; 46). The absence of signs of systemic cytomegalovirus infection argues against the diagnosis. Cytomegalovirus polyradiculopathy presents as involvement of lumbar and sacral roots (34) with symptoms such as sacral or sciatic pain, saddle paresthesias, distal sensory loss, progressive ascending motor weakness and marked sphincter dysfunction. Untreated, the condition worsens rapidly to flaccid paraparesis and areflexia (06; 30). Late in the course, the arms may be involved. A pure motor presentation with weakness, muscle wasting, and fasciculations has been described (30).

In a review of 103 AIDS patients with polyradiculopathy, hyporeflexia and leg weakness were seen in 100%, urinary retention in 94%, sensory loss in 80%, paresthesias in 79%, and lumbar pain in 36%. Rare presence of extensor plantar responses or sensory levels suggests associated spinal cord involvement by cytomegalovirus. Other organs were infected by cytomegalovirus in 44% (01).

Mononeuropathy multiplex has been described in 2 settings in HIV infection (52). A limited form (1 to 2 nerves) presents in HIV-seropositive patients without AIDS and represents a variant of HIV-related chronic inflammatory demyelinating polyneuropathy (32; 18; 28). A more generalized form (greater than 2 nerves) occurs in late AIDS, is rapidly progressive, and is often associated with cachexia and fever (40). Symptoms are asymmetric and involve the arms and legs (37). Initially, 1 or 2 nerves are infected with rapid progression to multiple nerves. Sensory symptoms with painful paresthesias can precede motor weakness by weeks to months. Cytomegalovirus has also been reported as causing a multifocal neuropathy, predominantly affecting the arms (14). Said and colleagues described multifocal inflammatory and necrotic lesions in peripheral nerve biopsies in 4 patients who developed a rapid progressive multifocal neuropathy with advanced HIV infection (41). One of the patients improved with ganciclovir; the other died soon after onset of neuropathy.

One unusual form of cytomegalovirus mononeuropathy involves the laryngeal nerve and presents as hoarseness (47). In 2 patients, hoarseness developed due to involvement of the recurrent laryngeal nerve during administration of ganciclovir for cytomegalovirus colitis. Postmortem examination of one patient showed cytomegalovirus infection throughout the body, including the recurrent laryngeal nerve. Cytomegalic cells were seen with acute and chronic inflammatory cell infiltration and edema. Another HIV seropositive patient with cytomegalovirus infection and polyradiculopathy presented with clinical and MRI evidence of cranial nerve involvement (25).

In a prospective study of 54 AIDS patients with peripheral nerve disease, which excluded patients with known exposure to neurotoxic drugs or other conditions associated with neuropathy, 38 had a distal symmetrical peripheral neuropathy; of these 25 had a painful, 13 a nonpainful neuropathy. In the group with pain 75% had temporally associated cytomegalovirus infection by antibody titers, compared to 37% in the control group with AIDS of similar severity without neuropathy. The painful neuropathy affected the legs more than the arms. Patients described severe burning or pins and needles sensation aggravated by touch and had altered touch or pin prick sensation. Symptoms progressed to maximum severity over 2 to 4 weeks and then remained stable or improved spontaneously (16). However, the association between sensory neuropathy and cytomegalovirus due to infection of and damage to the dorsal root ganglia leading to distal axonal degeneration (15; 13) remains controversial. Definitive evidence of cytomegalovirus in dorsal root ganglia is rare (43; 20). Although disseminated cytomegalovirus infection may contribute to peripheral nerve damage, possibly through an effect on endothelial cells and the microvasculature, it does not appear to be the primary cause of sensory neuropathy.

As mentioned, cytomegalovirus is linked to Guillain-Barré syndrome in the general, HIV seronegative population. Guillain-Barré syndrome is an acute inflammatory demyelinating polyradiculopathy that often follows nonspecific flu-like illnesses. In 1 study, antibody testing in Guillain-Barré syndrome patients revealed prior Campylobacter jejuni and cytomegalovirus infection in 23 and 8%, respectively (21), whereas cytomegalovirus antibodies were identified in 25% of such patients in another study (50). The disease is characterized by ascending paralysis evolving to maximum deficit over a period of about 2 to 4 weeks. Areflexia, sensory loss and dysesthesias, and autonomic dysfunction are commonly seen. Cytomegalovirus associated Guillain-Barré syndrome is associated with more prominent sensory involvement and severe disease (55; 21).

Patients who are immunosuppressed because of other disease processes or treatments are also at risk for cytomegalovirus disease. Although cytomegalovirus neuropathies are rare outside of the HIV-infected population, cytomegalovirus polyradiculopathy has been reported after bone marrow transplantation (57).

Prognosis and complications

Prognosis remains poor even with immune reconstitution and antivirals against cytomegalovirus. This is, in part, due to overall health of the patient (39).

Cytomegalovirus polyradiculopathy, if untreated, is rapidly fatal (100% mortality). In one review of cytomegalovirus polyradiculitis, 16 of 31 patients received ganciclovir; 3 patients stabilized, 6 improved. Of these, most had received ganciclovir within 2 weeks of symptom onset, and polymorphonuclear pleocytosis declined after induction therapy. Patients who failed to respond showed persistent polymorphonuclear pleocytosis, positive cultures and hypoglycorrhachia (05).

In another review of 103 patients with polyradiculomyelitis, mean survival in the untreated group was 5.4 ± 1.8 weeks compared to 14.6 ± 9.4 weeks in the group treated with ganciclovir, and 7.2 ± 3.0 weeks in patients already on ganciclovir at disease onset (01). Of 56 patients with cytomegalovirus polyradiculopathy who were treated with ganciclovir, 36% improved, 25% stabilized, and 39% continued to progress (01). Patients resistant to ganciclovir may respond to foscarnet, which is effective in ganciclovir-resistant cytomegalovirus retinitis, but there is little evidence as yet for to its efficacy in cytomegalovirus polyradiculomyelitis (26).

Biological basis

Etiology and pathogenesis

Cytomegalovirus has been associated with, and is thought to play a causal role in, polyradiculopathy, mononeuritis multiplex, and distal symmetrical polyneuropathy in patients with end-stage AIDS.

Cytomegalovirus is a ubiquitous double stranded DNA herpes virus. It causes a characteristic cytopathologic enlargement of host cells with intranuclear and cytoplasmic inclusion bodies. Some 50% to 90% of adults are antibody positive for cytomegalovirus. The virus establishes latency in hematogenous cells. It is found in saliva, breast milk, semen, vaginal secretions, and blood (23). Virus isolation from saliva or urine in a patient with neuropathy is difficult to interpret as causative, as it may represent nonspecific reactivation or simply chronic viral secretion (23).

A possible pathogenic mechanism may result from the ability of cytomegalovirus to trigger cryoglobulinemia (29).

Initial infection is generally asymptomatic. Symptomatic disease typically develops, when impaired T cell immunity leads to reactivation of latent cytomegalovirus infection. Although all human Herpes viruses can activate during HIV infection, this is most severe with cytomegalovirus. At autopsy some 50% of brains from AIDS patients show hallmarks of cytomegalovirus, ie, diffuse micronodular encephalitis and scattered microglial nodules containing cytomegalic cells or viral antigen (23).

In AIDS, direct cytomegalovirus infection of peripheral nerves occurs with infiltration by polymorphonuclear cells and necrotizing vasculitis of epineural arteries. Cytomegalovirus antigens, genome, and virions have been found within peripheral nerve and spinal ganglia of patients with polyradiculopathy, mononeuropathy multiplex, or peripheral neuropathy. Infectious targets may involve endothelial and Schwann cells, macrophages, and fibroblasts (28). Definitive evidence of cytomegalovirus in dorsal root ganglia, however, is rare (43; 20). Endothelial cell infection may result in ischemia or inflammatory damage with axonal degeneration and myelinated fiber loss (15; 07; 13). Furthermore, in patients with Guillain-Barré syndrome and antecedent cytomegalovirus (CMV) infection, Sawai and colleagues found autoantibodies against membrane-organizing extension spike protein (moesin) expressed by Schwann cells at the nodes of Ranvier (42). It connects the actin cytoskeleton to the extracellular matrix through transmembrane proteins, thus facilitating myelination. Moesin may be an immune target in the pathogenesis of cytomegalovirus-related Guillain-Barré syndrome.

Diagnostic workup

Imaging. Early in the course of cytomegalovirus polyradiculitis, imaging studies may be normal. Investigations need to include imaging of the cauda equina by myelography or MRI. This is always required to exclude lymphoma. In cytomegalovirus polyradiculopathy, MRI may be normal or show nodular thickenings on multiple roots with leptomeningeal enhancement from the conus medullaris to the cauda equina (51; 26; 30). Myelography may show arachnoiditis or crowding of nerve roots (26). In a review of 103 patients with diagnosis of cytomegalovirus polyradiculopathy, 31% had gadolinium enhancement and 17% an abnormal myelogram (01).

Laboratory studies. Cerebrospinal fluid analysis typically reveals high protein, low glucose, and polymorphonuclear pleocytosis. A review of 103 cases of AIDS and polyradiculopathy found the following mean values: WBC 651 ± 1,053 x 10-6 (with average of 68% polymorphonuclear granulocytes); protein 2.28 ± 1.78 g/L; CSF/serum glucose ratio 0.48 ± 0.17. Cytomegalovirus can be cultured in up to 50% of CSF samples (11; 45; 03; 34; 05). Cytomegalovirus can be cultured from CSF in up to 50% (11; 45; 03; 34; 05), and it can frequently be cultured from blood. Cytomegalovirus polymerase chain reaction is most sensitive for CSF diagnosis, with a sensitivity of 92% and a specificity of 94% (01). Cytologic analysis can exclude the presence of lymphoma cells and may occasionally demonstrate cytomegalic cells (19). Repeat lumbar puncture in difficult cases can be useful even if the initial CSF is normal. Occasionally, CSF evolves over 1 to 2 weeks from normal to abnormal after the onset of neurologic signs (05).

Branched chain DNA assays may be valuable in the future, as this may allow quantitation of cytomegalovirus in the CSF. It may allow to follow treatment responses, as viral DNA levels decrease before clinical improvement) and in identifying resistance to therapy early in the disease course (12).

Neurophysiological studies. Nerve conduction studies and EMG can be helpful in the confirmation of a clinical diagnosis of cytomegalovirus radiculopathy or mononeuropathy multiplex. It can, however, be challenging because of common neuromuscular comorbidities in AIDS, such as myopathies of different etiologies (46) or distal axonopathy.

In cytomegalovirus associated mononeuropathy multiplex, nerve conduction studies and EMG show reduced amplitudes of sensory nerve and compound muscle action potentials, mildly reduced conduction velocities, and denervation, often in an asymmetric distribution. Roullet and colleagues compared electrodiagnostic findings in 14 patients with cytomegalovirus mononeuritis multiplex with recordings from 90 nerves, 5 or more per patient (40). Evidence of axonal neuropathy was found with relative sparing of some nerves. Distal nerve syndromes were most prominent, but multiple radicular involvement was seen in some patients. Lowered compound muscle action potentials were recorded in 19 nerves with normal or mildly reduced nerve conduction velocities. F-waves were absent in 6 nerves and prolonged in 10. Sensory nerve action potentials were reduced in 17 nerves with normal or only mildly reduced nerve conduction velocities.

In cytomegalovirus associated polyradiculopathy, neurophysiological differentiation from other rapidly progressive neuropathies such as Guillain-Barré syndrome is important. Typical findings include widespread denervation, prolonged or absent F-waves, and low-amplitude or unobtainable tibial or peroneal compound motor action potentials, sometimes with normal sensory nerve action potentials from the affected areas (30).

Neuropathology. Neuropathological features in cytomegalovirus radiculopathy include necrosis and acute and chronic inflammation of the ventral and dorsal nerve roots, with cytomegalic cells and cytomegalovirus immunoreactivity in Schwann and endothelial cells as well as foci of microvascular thrombosis and inflammation (34). Necrotizing radiculomyelitis and focal myelitis with anterior horn cell loss can be seen; this spinal cord involvement is the likely basis of sensory levels and extensor plantars. In one autopsy series, cytomegalovirus was found in the peripheral nervous system, usually in endothelial cells, in 26% of AIDS patients as well as in 46% of those who had lived for greater than or equal to 2 years after the AIDS-defining illness (07).

Biopsies in cases of cytomegalovirus-related mononeuropathy multiplex can reveal marked vasculitic changes and centrofascicular degeneration.

Table 1. Diagnostic Pathway

Approach to the patient with lumbosacral polyradiculopathy and AIDS
	I. MRI and myelogram to exclude mass lesions
	II. CSF analysis
		A. If white blood cells > 50 and >40% polymorphonuclear granulocytes (or if polymerase chain reaction is positive for cytomegalovirus)
		B. If CSF is not suggestive of infection, but progression of weakness is rapid, proceed to empiric cytomegalovirus treatment
		C. If CSF is not suggestive and weakness is not rapidly progressive, monitor exam daily. If exam is worsening, consider empiric cytomegalovirus treatment.
		D. Repeat lymphocyte proliferation if there is no evidence of cytomegalovirus, but no other etiology is evident.
	III. Empiric treatment
		A. Ganciclovir is the first line of treatment
		B. If already on ganciclovir, start foscarnet (alone, or in addition to, ganciclovir)
Approach to the patient with peripheral neuropathy and HIV infection
	I. Nerve conduction studies and EMG
		A. Distal symmetrical polyneuropathy: evaluate for secondary causes, attempt correction, provide symptomatic treatment
		B. Inflammatory demyelinating polyneuropathy: assess level of immunosuppression.
			1. If immunosuppression is not advanced: immunotherapy
			2. If immunosuppression is advanced: CSF analysis
				a. Evidence of cytomegalovirus: anticytomegalovirus therapy
				b. No evidence of cytomegalovirus: nerve biopsy (consider anticytomegalovirus therapy if biopsy is negative)
		C. Mononeuropathy multiplex: if disease is extensive or with severe immunosuppression:
			1. CSF analysis:
				a. Evidence of cytomegalovirus: to anticytomegalovirus therapy
				b. No evidence of cytomegalovirus: nerve biopsy (consider anticytomegalovirus therapy if biopsy is negative)
		D. Progressive polyradiculopathy: CSF analysis:
			1. polymorphonuclear granulocyte predominance: anticytomegalovirus therapy
			2. mononuclear cell predominance: CSF cytology
				a. cytology suggestive of lymphoma: bone marrow biopsy, then radiation and chemotherapy if indicated
				b. cytology not suggestive of lymphoma: consider neurosyphilis

From (48)

Management

Therapy is urgent in all AIDS patients with cytomegalovirus-associated neurologic diseases and should be initiated immediately and empirically in patients with advanced HIV infection, rapidly progressive polyradiculopathy, and polymorphonuclear CSF pleocytosis. It must be continued indefinitely, even if no improvement is apparent (26). Ganciclovir 5 mg/kg IV every 12 hours or 2.5 mg/kg every 8 hours for 10 to 14 days is given for induction, followed by 5 mg/kg IV per day, 5 days per week for maintenance (30). CSF improvement with conversion to a lymphocytic predominance and reduced pleocytosis usually indicates a therapeutic response (05).

Foscarnet alone, or in addition to ganciclovir, should be tried in ganciclovir-resistant patients or those already on ganciclovir at the time of onset of polyradiculomyelitis. Ganciclovir resistance is suspected in patients with persistent pleocytosis on serial CSF analysis; branched-chain DNA assays may also be of value in identifying resistance to treatment. Foscarnet is prescribed at 60 mg/kg every 8 hours or 100 mg/kg q12h for 14 to 21 days, adjusted for renal function, followed by foscarnet 90 mg/kg per day.

Acyclovir is not used for cytomegalovirus polyradiculitis, as ganciclovir is approximately 26 times more potent against cytomegalovirus (09).

Valganciclovir is a prodrug of ganciclovir with equal oral and intravenous efficacy in cytomegalovirus retinitis. It is promising as an oral drug for cytomegalovirus polyradiculitis (09). Valganciclovir is used for cytomegalovirus prophylaxis, but at 900 mg daily, has a 10% to 40% risk of leucopenia, whereas 450 mg/day showed equal efficacy and fewer side effects (24)

Cidofovir has been used with some success in cytomegalovirus retinitis, but there is little evidence for efficacy in neurologic disease (33).

References

01: Anders HJ, Goebel FD. Cytomegalovirus polyradiculopathy in patients with AIDS. Clin Infect Dis 1998;27:345-52. PMID 9709885
02: Anders H, Weiss J, Bogner J, Goebel F. Ganciclovir and foscarnet efficacy in AIDS-related CMV polyradiculopathy. J Infect 1998;36:29-33. PMID 9515665
03: Behar R, Wiley c, McCutchan JA. Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 1987;37:557-61. PMID 3031543
04: Chavanet PY, Giroud M, Lancon, et al. Altered peripheral nerve conduction in HIV-patients. Cancer Detect Prev 1988;12:249-55. PMID 3180130
05: Cohen BA, McArthur JC, Grohman S, Patterson B, Glass JD. Neurologic prognosis in CMV polyradiculomyelopathy in AIDS. Neurology 1993;43:493-9. PMID 8383823
06: Cornblath DR, McArthur JC. Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988;28:794-6. PMID 2834669
07: Cornford ME, Ho HW, Vinters HV. Correlation of neuromuscular pathology in acquired immune deficiency syndrome patients with cytomegalovirus infection and zidovudine treatment. Acta Neuropathol 1992;84:516-29. PMID 1334328
08: Corral I, Quereda C, Casado J, et al. Acute polyradiculopathies in HIV-infected patients. J Neurol 1997;244:499-504. PMID 9309556
09: Curran M, Noble S. Valganciclovir. Drugs 2001;61:1145-50. PMID 11465875
10: Dowling PC, Cook SD. Role of infection in Guillain Barré syndrome: laboratory confirmation of herpes virus in 41 cases. Ann Neurol 1981;9(suppl):S44-55. PMID 6261680
11: Eidelberg D, Sotrel A, Vogel H, Walker P, Kleefield J, Crumpacker CS 3rd. Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 1986;36:912-6. PMID 3012412
12: Flood J, Drew L, Miner R, et al. Diagnosis of cytomegalovirus (CMV) polyradiculopathy and documentation of in vivo anti-CMV activity in cerebrospinal fluid by using branched DNA signal amplification and antigen assays. J Infect Dis 1997;176:348-52. PMID 9237699
13: Fuller GN. Cytomegalovirus and the peripheral nervous system in AIDS. J Acquir Immune Defic Syndr 1992;5(suppl 1):S33-6.
14: Fuller GN, Greco C, Miller RG. Cytomegalovirus in mononeuropathy multiplex in AIDS (abstract). Neurology 1990;40(suppl 1):301.
15: Fuller GN, Jacobs JM, Guiloff RJ. Association of painful peripheral neuropathy in AIDS with cytomegalovirus infection. Lancet 1989;2:937-41. PMID 2571861
16: Fuller GN, Jacobs JM, Guiloff RJ. Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry 1993;56(4):372-81. PMID 8387098
17: Gastaut JL, Gastaut JA, Pellissier JF, Tapko JB, Weill O. Neuropathies with HIV infection. Prospective study of 56 cases. Revue Neurol 1989;145:451-9. PMID 2552560
18: Gherardi R, Lebargi F, Gaulard P, Mhiri C, Bernaudin JF, Gray F. Necrotizing vasculitis and HIV replication in peripheral nerves (letter). N Engl J Med 1989;321:685-6. PMID 2570352
19: Glass JD, Erozan YS. Rapid diagnosis of cytomegalovirus polyradiculitis in a patient with acquired immunodeficiency syndrome. Ann Neurol 1993;34:239. PMID 8393315
20: Griffin JW, Crawford TO, Glass JD, Price DL, Cornblath DR, McArthur JC. Sensory neuropathy in AIDS: I. Neuropathology. Brain 1994.
21: Hadden RD, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barré syndrome. Neurology 2001;56:758-65. PMID 11274311
22: Jakobsen J, Smith T, Gaub J, Helweg-Larsen S, Trojaborg W. Progressive neurological dysfunction during latent HIV infection. Br Med J 1989;299:225-8. PMID 2548647
23: Johnson RT. Herpesvirus infections. Viral Infections of the nervous system. 2nd ed. Baltimore: Lippincott-Raven, 1998:164-7.
24: Kalil AC, Mindru C, Florescu DF. Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis. Clin Infect Dis 2011;52(3):313-21. PMID 21189424
25: Kenyon LC, Goldberg HI, Kolson DL, Collman RG, Lavi E. Case of the month: May 1998 - A patient with HIV infection and multiple cranial neuritis. Brain Pathol 1998;8:815-6. PMID 9804388
26: Kim YS, Hollander H. Polyradiculopathy due to cytomegalovirus: report of two cases in which improvement occurred after prolonged therapy and review of the literature. Clin Infect Dis 1993;17(1):32-7. PMID 8394748
27: Klemola E, Weckman N, Haltia K, Kaariainen. The Guillain-Barré syndrome associated with acquired cytomegalovirus infection. Acta Med Scand 1967;181(5):603-7. PMID 4290616
28: Kolson DL, Gonzalez-Scarano F. HIV-associated neuropathies: role of HIV-1, CMV, and other viruses. J Peripher Nerv Syst 2001;6:2-7. PMID 11293803
29: Kramer J, Hennig H, Lensing C, et al. Multi-organ affecting CMV-associated cryoglobulinemic vasculitis. Clin Nephrol 2006;66:284-90. PMID 17063996
30: Lange DJ. Neuromuscular diseases associated with HIV-1 infection. Muscle Nerve 1994;17:16-30. PMID 8264698
31: Lanska MJ, Lanska DJ, Schmidley JW. Syphilitic polyradiculopathy in an HIV-positive man. Neurology 1988;38:1297-301. PMID 2840606
32: Lipkin WI, Parry G, Kiprov D, Abrams D. Inflammatory neuropathy in homosexual men with lymphadenopathy. Neurology 1985;35:1479-83. PMID 2993951
33: Maschke M, Kastrup O, Diener H. CNS manifestations of cytomegalovirus infections. CNS Drugs 2002;16:303-15. PMID 11994020
34: Miller RG, Storey JR, Greco CM. Ganciclovir in treatment of progressive AIDS-related polyradiculopathy. Neurology 1990;40:569-74. PMID 2157172
35: Orlikowski D, Porcher R, Sivadon-Tardy V, et al. Guillain-Barre syndrome following primary cytomegalovirus infection: a prospective cohort study. Clin Infect Dis 2011;52(7):837-44. PMID 21427390
36: Raphael SA, Price ML, Lischner HW, Griffen JW, Grover WD, Bagasra O. Inflammatory demyelinating polyneuropathy in a child with symptomatic human immunodeficiency virus infection. J Pediatr 1991;118:242-5. PMID 1993952
37: Reus S, Boix V, Priego M, Merino E, Portilla J. Cytomegalovirus polyradiculopathy presenting as bilateral radial nerve palsies in a patient with AIDS. Eur J Clin Microbiol Infect Dis 1999;18:605-6. PMID 10517204
38: Robert ME, Geraghty JJ 3rd, Miles SA, Cornford ME, Vinters HV. Severe neuropathy in a patient with acquired immune deficiency syndrome (AIDS). Evidence for widespread cytomegalovirus infection of peripheral nerve and human immunodeficiency virus-like immunoreactivity of anterior horn cells. Acta Neuropathol 1989;79(3):255-61. PMID 2558484
39: Robinson-Papp J, Simpson David M. Neuromuscular diseases associated with HIV-1 infection. Muscle Nerve 2009;40:1043-53. PMID 19771594
40: Roullet E, Asseurus V, Gozlan J, et al. Cytomegalovirus multifocal neuropathy in AIDS: Analysis of 15 consecutive cases. Neurology 1994;44:2174-82. PMID 7969979
41: Said G, Lacroix C, Chemouilli P, et al. Cytomegalovirus neuropathy in acquired immunodeficiency syndrome: a clinical and pathological study. Ann Neurol 1991;29:139-46. PMID 1849386
42: Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome. Neurology 2014;83(2):113-7. PMID 24920858
43: Scaravilli F, Sinclair E, Arango JC, Manji H, Lucas S, Harrison MJ. The pathology of the posterior root ganglia in AIDS and its relationship to the pallor of the gracile tract. Acta Neuropathol (Berl) 1992;84(2):163-70. PMID 1326204
44: Simpson DM. Selected peripheral neuropathies associated with human immunodeficiency virus infection and antiretroviral therapy. J Neurovir 2002;8:33-41. PMID 12491149
45: Singh BM, Levine S, Yarrish RL, Hyland MJ, Jeanthy D, Wormser GP. Spinal cord syndromes in the acquired immune deficiency syndrome. Acta Neurol Scand 1986;73:590-8. PMID 3019071
46: Singh NN, Thomas FP. Progressive Polyradiculopathy in HIV. www.eMedicine.com. Accessed 2013.
47: Small PM, McPhaul LW, Sooy CD, Wofsy CB, Jacobson MA. Cytomegalovirus infection of the laryngeal nerve presenting as hoarseness in patients with acquired immunodeficiency syndrome. Am J Med 1989;86:108-10. PMID 2535917
48: So Y, Olney R. Acute lumbosacral polyradiculopathy in acquired immunodeficiency syndrome: Experience in 23 patients. Ann Neurol 1994;35:53-8. PMID 8285593
49: So YT, Holtzman DM, Abrams DI, Olney RK. Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population-based survey. Arch Neurol 1988;45:945-8. PMID 2843154
50: Steininger C, Seiser A, Gueler N, et al. Primary cytomegalovirus infection in patients with Guillain-Barré syndrome. J Neuroimmunol 2007;183:214-9. PMID 17184845
51: Talpos D, Tien RD, Hesselink JR. Magnetic resonance imaging of AIDS-related polyradiculopathy. Neurology 1991;41:1996-7. PMID 1660573
52: Thomas FP. HIV-1 associated multiple mononeuropathies. www.eMedicine.com. Accessed 2013.
53: Thomas FP, Singh NN. Neuromuscular and Myopathic Complications of HIV. www.eMedicine.com. Accessed 2013.
54: Thongpooswan S, Chyn E, Alfishawy M, et al. Polyradiculopathy and gastroparesis due to cytomegalovirus infection in AIDS: a case report and review of literature. Am J Case Rep 2015;16:801-4. PMID 26552851
55: van der Meche FG, Visser LH, Jacobs BC, Endtz HP, Meulstee J, van Doorn PA. Guillain-Barré syndrome: Multifactorial mechanisms versus defined subgroups. J Infect Dis 1997;176:S99-102. PMID 9396690
56: Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy. Drugs 2000;59:1251-60. PMID 10882161
57: Zeiser R, Grullich C, Bertz H, et al. Late cytomegalovirus polyradiculopathy following haploidentical CD34+-selected hematopoietic stem cell transplantation. Bone Marrow Transplant 2004;33(2):243-5. PMID 14716290

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Niranjan N Singh MD

Dr. Singh of the University of Missouri-Columbia received honorariums from AbbVie for speaking engagements.
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Florian P Thomas MD MA PhD MS

Dr. Thomas of Hackensack Meridian School of Medicine had no relevant financial relationships to disclose.
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Editor

Louis H Weimer MD

Dr. Weimer of Columbia University has no relevant financial relationships to disclose.
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Former Authors

Justin C McArthur MD
Laura Schaben MD
Pavan Tummala MD MS

Patient Profile

Age range of presentation: 0-01 month

01-23 months

02-05 years

06-12 years

13-18 years

19-44 years

45-64 years

65+ years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: immunodeficient adults (ie, AIDS patients)

transplant patients
Occupation groups selectively affected: none identified

ICD & OMIM codes

ICD-9: Cytomegalovirus disease: 078.5

Guillain Barré syndrome: 357.0

Hereditary sensory radicular neuropathy: 356.2

Lumbosacral neuropathy: 724.4

Mononeuritis of unspecified site: 355.9

Polyneuropathy in collagen vascular disease: 357.1

Radiculitis: 729.2

Unspecified idiopathic peripheral neuropathy: 356.9
ICD-10: Cytomegaloviral disease, unspecified: B25.9

Guillain Barré syndrome: G61.0

Hereditary and idiopathic neuropathy, unspecified: G60.9

Lumbosacral neuropathy: M54.14

Mononeuropathy, unspecified: G58.9

Neuralgia and neuritis, unspecified: M79.2

Polyneuropathy in systemic connective tissue disorders: G63.5

Radiculitis NOS: M54.1

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Neuropathies associated with cytomegalovirus infection

Associated Disorders

AIDS
Cauda equina syndrome
Cytomegalovirus neuropathy
Cytomegalovirus polyradiculitis
Cytomegalovirus polyradiculopathy
- Cytomegalovirus radiculitis
- Cytomegalovirus radiculopathy
- Guillain-Barré syndrome

Differential Diagnosis

diabetic neuropathies
neurosyphilis
lymphomatous meningitis
cryptococcus
toxoplasmosis
- tuberculosis of the conus medullaris
- lymphomatous spinal masses
- Herpes simplex virus-2
- Varicella zoster virus
- HIV inflammatory polyradiculitis
- acute lumbosacral polyradiculopathy
- metastatic systemic lymphoma
- Kaposi sarcoma
- toxoplasmosis
- spinal disc syndromes
- central disc prolapse
- B12 and folate deficiency
- thyroid disorders
- malnutrition
- paraneoplastic disorders
- Herpes simplex virus ganglioneuritis
- direct HIV effect
- drug toxicity

Also Relevant

Acquired cytomegalovirus
Autistic spectrum disorders
Congenital cytomegalovirus
Congenital lymphocytic choriomeningitis virus infection
Headache associated with AIDS
- HIV-associated dementia
- Microcephaly
- Molecular diagnosis of central nervous system infections
- Vaccines for neurologic disorders
- Viral meningitis

Neuropathies associated with cytomegalovirus infection …

Neuropathies associated with cytomegalovirus infection

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Table 1. Diagnostic Pathway

Management

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

Genital herpes: neurologic complications

Zika virus: neurologic complications

Gram-negative bacillary meningitis

Chronic inflammatory demyelinating polyradiculoneuropathy

Amyotrophic lateral sclerosis

Amiodarone neuropathy

Pneumococcal meningitis

Autoimmune autonomic neuropathy

Neuropathies associated with cytomegalovirus infection

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Table 1. Diagnostic Pathway

Management

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Genital herpes: neurologic complications

Zika virus: neurologic complications

Gram-negative bacillary meningitis

Chronic inflammatory demyelinating polyradiculoneuropathy

Amyotrophic lateral sclerosis

Amiodarone neuropathy

Pneumococcal meningitis

Autoimmune autonomic neuropathy

This is an article preview.
Start a Free Account
to access the full version.