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Ascending paralysis associated with HIV infection.

About 34 million people are affected with HIV worldwide as of 2010, including more than 1.1 million in the United States (1). The immune impairment manifests clinically in multiple organ systems including the nervous system. Since the introduction of highly active antiretroviral therapy (HAART), HIV has evolved into a chronic condition with an increase in related complications (2). Neurologic complications occur in more than 40% of patients with HIV infection, and the prevalence of neuropathologic findings at autopsy is about 80% (3, 4). Central and peripheral nervous system involvement in HIV-infected patients occurs due to various causes, including opportunistic infections, immune reconstitution, a side effect of antiretroviral medication, or the effect of the virus (5). The variations might be due to a difference in age, disease stage, treatment history, timing of the study (i.e., pre- or post-HAART era), and the diagnostic criteria used in different studies. We present two cases of ascending paralysis in HIV-positive patients. Not only was the autoimmune nature of Guillain-Barre syndrome (GBS) in the setting of an immunocompromised patient remarkable, but more importantly the improvement seen in both patients required different treatment approaches.

CASE 1

A 33-year-old white man presented with a 1-day history of bilateral lower-extremity weakness, numbness, and a tingling sensation that started in his feet and progressed to his knees and very soon involved his fingertips bilaterally. The patient was diagnosed with HIV 1 week earlier during evaluation of a flulike illness including fever, chills, and maculopapular rash with diarrhea. His HIV viral load was 2,095,380 copies/mL, with a CD4 count of 526 cells/[micro]L (Table 1). Baseline genotype testing done at that time showed no drug resistance. His past medical history was unremarkable. Examination disclosed intact cognition, intact cranial nerves, decreased sensation in the lower extremities bilaterally up to the knees, along with decreased sensation on the palmar aspect of the hands bilaterally. Muscle strength was slightly decreased bilaterally in the deltoids. Patellar, Achilles, and biceps deep tendon reflexes were absent, with only the triceps jerk detected at presentation. Cerebrospinal fluid (CSF) analysis in the emergency department showed elevated proteins with mild lymphocytic pleocytosis (Table 2). Based on his presentation and CSF findings, he was started on intravenous immunoglobulin (IVIG) the day of admission for possible acute inflammatory demyelinating polyneuropathy (AIDP). Within the first few days of admission, he was also started on HAART with Truvada, raltegravir, darunavir, and ritonavir. The CSF was positive for mycoplasma IgG antibodies (1:4 titer) with negative IgM. However, the test for serum mycoplasma IgM was positive, and hence the patient was started on levofloxacin. The results of magnetic resonance imaging (MRI) of the brain and cervical spine without contrast were unremarkable.

The patient's ascending paralysis worsened over the next 3 days with paresthesias, loss of all deep tendon reflexes, and involvement of cranial nerves. He completed a full course of IVIG of 2 g/kg over 3 days but continued to deteriorate and was started on a five-cycle regimen of plasmapheresis on day 5. Despite aggressive daily plasmapheresis for three cycles, he continued to worsen with autonomic instability, flaccid quadriplegia, and respiratory failure requiring endotracheal intubation and mechanical ventilation 8 days after admission. Four days after intubation, the patient fairly quickly recovered his respiratory muscle strength and was extubated. A repeat HIV viral load test after 1 week of HAART showed only 3590 copies/mL.

A nerve conduction study (NCS) and electromyogram (EMG) performed 15 days after presentation showed evidence of an acquired sensory and motor peripheral neuropathy with mixed axonal and demyelinating features. There was also diffuse early denervation indicating secondary axonal loss. The relative paucity of denervation seen on the EMG/NCS exam likely reflected the short time lapse since the onset of symptoms.

The patient continued to gradually regain his muscular function and was transferred to a skilled nursing facility for continuing physical therapy. After a 4-week stay at the facility, his muscle strength was close to baseline, and he was discharged home.

CASE 2

A 37-year-old white man with a history of HIV/AIDS with a last CD4 count of 22 cells/pL (Table 1) presented to the emergency department with 4 weeks of progressively worsening ascending weakness, tingling, and numbness of his lower extremities, with gradual involvement of his upper extremities. He had a history of recurrent lower-extremity weakness and decreased sensation that had required previous hospitalizations. His past medical history was significant for anemia, several episodes of gastritis, asthma, past hepatitis B infection, and anxiety. His family history was not significant for any neurological diseases. Examination disclosed a cognitively intact man with intact cranial nerves. There was a lack of sensation to light touch in the feet and numbness in the hand bilaterally. Grip strength was weak in both hands with trace finger abduction. Elbow flexion and extension was 3/5 and shoulder flexion was 2/5. Reflexes were absent in both upper and lower extremities. MRI scans of the brain and spine were unremarkable. CSF evaluation revealed classic albuminocytologic dissociation without any signs of active infection (Table 2).

NCS and EMG tests 20 days after hospitalization showed diffuse sensory motor polyneuropathy with both demyelinating and axonal features. The patient was started on HAART with Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) and given 2 days of IVIG. Soon after starting IVIG, the patient showed clinical improvement. He was transferred for rehabilitation after a 1-week hospital stay for aggressive physical therapy. Since his initial presentation about a year ago, he has been rehospitalized twice with similar symptoms despite being on continual HAART, during which his viral load has been very low (varying from <20 copies/mL up to 1510 copies/mL). His symptoms continue to respond to treatment with IVIG. Repeated CSF evaluations reveal cytoalbuminologic dissociation at varying degrees (white cells range from 2 to 8/[mu]L, and protein ranges from 114 to 331 mg/dL). Although the patient started out with AIDP with axonal features, he now carries the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP).

DISCUSSION

These two cases of HIV illustrate very similar clinical presentations with very different pathophysiologies and long-term outcomes. The CSF and HIV status findings dictated very different treatment regimens. In case 1, the patient had aseptic meningitis with multiple possible etiologies (HIV, mycoplasma, seroconversion) and improved only after his HIV RNA titers came down in a monophasic pattern of illness. In the second case, the patient did not have meningitis but rather had what is now known to be CIDP with recurrent symptoms responding very well to IVIG.

HIV can be neuroinvasive, neurotropic, and neurovirulent. Many peripheral neuropathic syndromes have been reported in the context of HIV infection, including HIV-associated distal sensory neuropathy, neurotoxic nucleoside neuropathy, and inflammatory demyelinating neuropathy. HIV-associated distal sensory polyneuropathy (also called predominantly sensory neuropathy, or distal symmetrical peripheral neuropathy) is the most common neurological problem in AIDS, with variable incidences in different reports ranging from 19% to 66% (6, 7). The risk factors for HIV-associated distal sensory polyneuropathy are older age, history of alcohol abuse, advanced HIV disease, prior use of a neurotoxic antiretroviral drug, and diabetes mellitus (8, 9). Inflammatory demyelinating neuropathy, on the other hand, is less common and can occur at various stages of the disease, requiring different therapeutic approaches.

Both patients presented with an ascending paralysis typically described with clinical GBS. GBS generally follows an infectious prodrome, resulting in an augmented immune response, which cross-reacts with axolemmal or Schwann cell antigens, leading to peripheral nerve damage believed to be due to molecular mimicry. The clinical features of GBS are progressive, ascending, fairly symmetric muscle weakness, typically with absent reflexes. The severity of symptoms can vary from mild to profound weakness of all extremities and involving respiratory muscles, resulting in respiratory failure requiring intubation. Respiratory failure requiring ventilator support occurs in 10% to 30% of the cases (10). Symptoms can also include tachycardia, urinary retention, labile blood pressure, arrhythmias, and paresthesias more commonly seen on fingertips and feet and can include autonomic instability in severe cases. The hallmark laboratory finding is albuminocytologic dissociation on the CSF with a near normal white blood cell count seen in up to 66% of patients (11). Treatment for GBS typically involves IVIG or plasmapheresis, which have been shown to have similar outcomes. In our first patient, intrathecal IgG synthesis was dramatically elevated, suggesting an ongoing immune-mediated process, which did not improve until his viral load came down. Notably, he recovered very rapidly (walking within a week after tetraplegia). This was much faster than could be expected in typical GBS patients who have significant changes, both demyelinating and axonal, on NCS/EMG.

GBS in an HIV/AIDS patient was first described in 1985 (12). GBS may occur in HIV-infected patients at the time of seroconversion, even with normal CD4 counts, and can be the presenting symptom or seen in the setting of the immune reconstitution syndrome (13-16). Nucleoside analogue reverse transcriptase inhibitors (NRTIs), a backbone component of HAART, have also been related to GBS in HIV-infected individuals in association with the immune reconstitution syndrome. Twenty-two cases of GBS associated with stavudine (NRTI) therapy have been reported (17-19).

Several mechanisms have been proposed regarding GBS in HIV-infected patients. Proposed mechanisms include a direct action of HIV on the nerve by neurotropic strains or formation of autoantibodies against myelin secondary to the abnormal immunoregulation caused by the HIV infection (20). In the setting of immune reconstitution syndrome, there is a reemergence of previously anergic lymphocytes upon viral suppression with HAART (13-16). Cell-mediated immunity is known to play a major role in the pathogenesis of GBS. The clinical features of GBS in HIV-infected patients are similar to those in HIV-negative people. However, HIV GBS may be associated with more frequent recurrent episodes and progression to CIDP (21).

In our first case, the onset of rapidly progressive ascending paralysis coincided with the acute retroviral syndrome of HIV. This patient continued to worsen despite IVIG therapy and plasma exchange and only improved with the initiation of HAART and reduction in the viral load. We have not found any previous reports specifically addressing the efficacy of either IVIG or plasmapheresis in the setting of acute retroviral syndrome, but previously reported cases and our first case suggest that antiretroviral treatment is preferable especially if CSF findings show the presence of meningeal inflammation. In our second case, the patient with chronic HIV infection had clinical symptoms consistent with AIDP and ultimately CIDP with modest recovery only seen with IVIG. IVIG has been shown to speed the course of recovery in patients with GBS and HIV seropositivity. Reports of efficacy range from ineffective or mild benefit to a great response (22). In the first case, mycoplasma tested positive and in the second case cytomegalovirus was positive. Both cytomegalovirus and mycoplasma have been implicated in ascending paralysis. It is fairly common to have several potential causes for similar presentations in HIV patients with neurological complications, which exemplifies the complexity of HIV patients.

Aasim Afzal, MD, MBA, Mina Benjamin, MD, Kyle L. Gummelt, DO, MPH, Sadaf Afzal, MBBS, Sadat Shamim, MD, and Marc Tribble, MD

From the Department of Internal Medicine (Afzal, Benjamin, Gummelt), the Division of Neurology (Shamim), and the Division of Infectious Diseases (Tribble), Baylor University Medical Center at Dallas.

Corresponding author: Sadat Shamim, MD, 3600 Gaston Avenue, Suite 1155, Dallas, TX 75246 (e-mail: SadatSha@BaylorHealth.edu).

(1.) Nishijima T, Tsukada K, Takeuchi S, Chiba A, Honda M, Teruya K, Gatanaga H, Kikuchi Y, Oka S. Antiretroviral therapy for treatment-naive chronic HIV-1 infection with an axonal variant of Guillain-Barre syndrome positive for anti-ganglioside antibody: a case report. Intern Med 2011; 50(20):2427-2429.

(2.) Centers for Disease Control and Prevention. Estimated HIV incidence in the United States, 2007-2010. HIV Surveillance Supplemental Report 2012; 17(4). Available at http://www.cdc.gov/hiv/pdf/statistics_hssr_ vol_17_no_4.pdf; accessed October 2014.

(3.) de Gans J, Portegies P. Neurological complications of infection with human immunodeficiency virus type 1. A review of literature and 241 cases. Clin Neurol Neurosurg 1989; 91(3):199-219.

(4.) Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. New York: Chapman & Hall, 1998.

(5.) Ghosh S, Chandran A, Jansen JP. Epidemiology of HIV-related neuropathy: a systematic literature review. AIDS Res Hum Retroviruses 2012; 28(1):36-48.

(6.) Verma S, Estanislao L, Simpson D. HIV-associated neuropathic pain: epidemiology, pathophysiology and management. CNS Drugs 2005; 19(4):325-334.

(7.) Letendre SL, Ellis RJ, Everall I, Ances B, Bharti A, McCutchan JA. Neurologic complications of HIV disease and their treatment. Top HIV Med 2009; 17(2):46-56.

(8.) Lopez OL, Becker JT, Dew MA, Caldararo R. Risk modifiers for peripheral sensory neuropathy in HIV infection/AIDS. Eur J Neurol 2004; 11(2):97-102.

(9.) Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD; HIV Outpatient Study Investigators. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis 2005; 40(1):148-157.

(10.) Sejvar JJ, Baughman AL, Wise M, Morgan OW Population incidence of Guillain-Barre syndrome: a systematic review and meta-analysis. Neuroepidemiology 2011; 36(2):123-133.

(11.) Yuki N, Hartung HP. Guillain-Barre syndrome. N Engl J Med 2012; 366(24):2294-2304.

(12.) Mishra BB, Sommers W, Koski CL, Greenstein JI. Acute inflammatory demyelinating polyneuropathy in the acquired immune deficiency syndrome. Ann Neurol 1985; 18:131-132.

(13.) Hirsch HH, Kaufmann G, Sendi P, Battegay M. Immune reconstitution in HIV-infected patients. Clin Infect Dis 2004; 38(8):1159-1166.

(14.) Makela P, Howe L, Glover S, Ferguson I, Pinto A, Gompels M. Recurrent Guillain-Barre syndrome as a complication of immune reconstitution in HIV. J Infect 2002; 44(1):47M9.

(15.) Piliero PJ, Fish DG, Preston S, Cunningham D, Kinchelow T, Salgo M, Qian J, Drusano GL. Guillain-Barre syndrome associated with immune reconstitution. Clin Infect Dis 2003; 36(9):e111-e114.

(16.) Teo EC, Azwra A, Jones RL, Gazzard BG, Nelson M. Guillain-Barre syndrome following immune reconstitution after antiretroviral therapy for primary HIV infection. J HIV Ther 2007; 12(3):62-63.

(17.) Bristol-Myers Squibb. Zerit(Stavudine) [Product information]. Princeton, NJ: Bristol-Myers Squibb, 2006.

(18.) Shah SS, Rodriguez T, McGowan JP Miller Fisher variant of GuillainBarre syndrome associated with lactic acidosis and stavudine therapy. Clin Infect Dis 2003; 36(10):e131-e133.

(19.) Wooltorton E. HIV drug stavudine (Zerit, d4T) and symptoms mimicking Guillain-Barre syndrome. CMAJ 2002; 166(8):1067.

(20.) Pontali E, Feasi M, Crisalli MP, Cassola G. Guillain-Barre syndrome with fatal outcome during HIV-1-seroconversion: a case report. Case Rep Infect Dis 2011; 2011:972096.

(21.) Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barre syndrome. J Neurol Sci 2003; 208(1-2):39-42.

(22.) Hassan KM, Mathew I. Guillain Barre syndrome--in an HIV seropositive subject. J Assoc Physicians India 2000; 48(12):1214.
Table 1. Blood work

Blood laboratory test           Patient 1   Patient 2

CD4 count (cells/gL)            526         22
HIV PCR (copies/mL)             2,095,380   59,200
Rapid plasma reagin             Negative    Negative
Human herpesvirus 6 PCR         Negative    N/A
Herpes simplex virus PCR        Negative    Negative
Varicella-zoster virus IgM      Negative    N/A
Lyme antibody                   Negative    N/A
Monospot                        Negative    N/A
Cytomegalovirus PCR             N/A         Positive
Toxoplasma IgG and IgM          N/A         Negative
Thyroid-stimulating hormone     Normal      Normal
Folic acid                      Normal      Normal
Vitamin B12                     Normal      Normal
Serum protein electrophoresis   Negative    Negative
Ganglioside antibody panel      Negative    N/A
Heavy metal screen              Negative    Negative

PCR indicates polymerase chain reaction; Ig, immunoglobulin.

Table 2. Initial cerebrospinal fluid data

Laboratory test                        Patient 1     Patient 2

Protein (mg/dL)                        109           331
Glucose (mg/dL)                        52            54
White blood cells (cells/gL)           35 (89%       8 (52%
                                       lymphocyte)   lymphocyte)
Red blood cells (cells/gL)             N/A           4000
Gram stain                             Negative      Negative
IgG synthesis                          Elevated      N/A
Oligoclonal bands                      Negative      Negative
Adenovirus                             Negative      N/A
Epstein-Barr virus IgM                 Negative      Negative
Varicella zoster virus PCR             Negative      Negative
Herpes simplex virus PCR               N/A           Negative
Cocksackie A/B PCR                     Negative      Negative
Cytomegalovirus PCR                    Negative      Negative
Cryptococcal antigen                   Negative      Negative
West Nile antibody                     Negative      Negative
Cytology                               Negative      Negative
Venereal Disease Research Laboratory   Negative      Negative
Bacterial culture                      Negative      Negative
HIV PCR (copies/mL)                    N/A           2142
Mycoplasma IgG                         1:4           N/A
Mycoplasma IgM                         Negative      N/A

PCR indicates polymerase chain reaction; Ig, immunoglobulin.
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Author:Afzal, Aasim; Benjamin, Mina; Gummelt, Kyle L.; Afzal, Sadaf; Shamim, Sadat; Tribble, Marc
Publication:Baylor University Medical Center Proceedings
Article Type:Report
Geographic Code:1USA
Date:Dec 27, 2014
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