Multiple mononeuropathies (Mononeuritis Multiplex) are characterized by sensory disturbances and/or weakness in the distribution of ≥ 2 affected peripheral nerves.[1] Multiple mononeuropathies is usually secondary to:
Presentation of multiple peripheral mononeuropathies in the setting of HIV-1 disease can be similar to multiple mononeuropathies in the non-HIV population. Early multiple mononeuropathies are usually self-limited and can present at the time of seroconversion.[2] Late multiple mononeuropathies in a patient with a CD4 count less than 50 cells/mm3 is usually related to cytomegalovirus (CMV) infection and can progress rapidly.[2, 3, 4, 5, 6, 7, 8, 9, 10]
A limited form of multiple mononeuropathies (1–2 nerves) presents in HIV-seropositive patients without AIDS and may have an autoimmune origin. A more generalized form (>2 nerves) presents in patients with AIDS. While CMV is often shown to be the cause, the occurrence of clinical CMV in AIDS has declined with the advent of antiretroviral therapy (ART).
The most common cranial mononeuropathy in HIV patients involves the facial nerve usually occurring around the time of seroconversion. Conditions known to accompany HIV such as CNS (central nervous system) lymphoma, diffuse infiltrative lymphocytosis syndrome, tuberculosis meningitis, syphilis, HSV-1, VZV, and vasculitis can also cause various cranial mononeuropathies.
Herpes zoster can occur in HIV patients in the form of trigeminal neuropathy. This is classically associated with zoster vesicles with dermatomal distribution. Various cranial neuropathies involving the trochlear nerve, facial nerve, and mental branch of the trigeminal nerve can be associated with CNS lymphomas.[11, 12, 13] Diffuse infiltrative lymphocytosis syndrome can cause facial palsy.[14, 11] Optic neuropathy has been reported in syphilis.[15] Entrapment neuropathies can occur in advanced HIV disease.
The multiple mononeuropathies are typically inflammatory in nature and may involve single or multiple cranial or peripheral nerves. They vary with the stage of HIV infection.[16]
The patient describes multifocal asymmetric sensory or motor complaints in the distribution of cranial nerves,[3] peripheral nerves, or nerve roots.
Pure motor nerve involvement begins with painless weakness; pure sensory nerve involvement begins with sensory disturbances and no weakness. Multiple mononeuropathies are often asymmetric at first; nerves may be involved all at once or progressively. Extensive involvement of many nerves may simulate polyneuropathy.[17]
Cranial neuropathies most commonly involve the facial nerve (also known as Bell's palsy) and can be unilateral or bilateral. Facial paralysis in HIV patients does not differ clinically from typical Bell's palsy.
Physical findings include asymmetric weakness and reflex and sensory loss. More severe involvement suggests cytomegalovirus (CMV) infection. Progression may change presentation from multifocal mononeuropathies to a more generalized polyneuropathy.
Classic mononeuropathy multiplex with painful, stepwise, multifocal deficits is well described in patients with advanced AIDS and cytomegalovirus (CMV) infection. A milder form of mononeuropathy multiplex, involving one or a few nerves, occurs in HIV without CMV coinfection. It is most often self-limited and usually resolves after several months. The underlying etiology is probably autoimmune, and this syndrome may be thought of as a variant of inflammatory demyelinating polyneuropathy (IDP) with more prominent axonal features. Accordingly, immunomodulatory treatment such as corticosteroids, plasmapheresis, or intravenous immunoglobulin may provide benefit.[17]
Acute CMV infection in immunocompetent people is either asymptomatic or associated with a mild febrile illness. Following initial infection, CMV remains latent unless significant immunocompromise occurs. In the immunocompromised patient, CMV can infect peripheral nerves directly, leading to inflammation and necrosis.[18]
Blood for CMV polymerase chain reaction (PCR) analysis should be sent if HIV-associated multiple mononeuropathies are suspected.[19]
A positive CMV PCR in CSF, evidence of CMV on nerve biopsy, or evidence of CMV infection in other organs (such as CMV retinitis) supports the diagnosis.[20]
Electromyographic (EMG) and nerve conduction studies show asymmetric multifocal involvement with axonal degeneration, and the CSF will show an elevated protein level and pleocytosis.
Cerebral spinal fluid may indicate the following:
Electromyography/nerve conduction studies may indicate the following:
Correlation with CD4+ lymphocyte counts (a surrogate marker for stage of HIV infection) may indicate the following:
Histologic findings show axonal degeneration with perivascular mononuclear infiltrates. Occasionally, the infiltrate is predominantly polymorphonuclear.
In patients with multiple mononeuropathies due to CMV infection, CMV inclusions can be seen in mononuclear and endothelial cells, and CMV can be identified by culture or polymerase chain reaction. Occasionally, a prominent necrotizing arteritis can be seen.
Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange) are preferred to immunosuppression. During a 7- to 10-day period, 4–5 plasmaphereses may be performed, as described in standard protocols. Potential complications include autonomic instability, hypercalcemia, and bleeding from depletion of clotting factors. The decision whether to use IVIG, plasmapheresis, or steroids should be based on the individual patient.[21, 22]
Treatment for mononeuropathies that are secondary to other co-existing conditions require focused therapy specific to that underlying organism or condition. For example, a more extensive disease state resulting from disseminated CMV infection can be treated with ganciclovir and/or foscarnet if instituted early.
In patients with positive CMV who are immunocompromised due to AIDS, immune reconstitution with antiretroviral therapy (ART) should be attempted.[18]
Conversely, the limited autoimmune form can be treated with IVIG, plasmapheresis, or steroids. These treatments have proven efficacious in some studies but not in others.
Facial palsy recovery is similar to those without HIV and typically self-resolve.
ART has been shown to improve symptoms in patients with presumed HIV-induced optic neuropathy.[23]