Focal monophasic demyelinating leukoencephalopathy in advanced HIV infection

A multiple sclerosis (MS)-like illness has been reported in human immunodeficiency virus (HIV)-infected patients, usually in the early stages of HIV infection. We report 3 patients with advanced HIV infection (CD4 lymphocyte count under 200/mm(3)) presenting with monophasic focal leukoencephalopathy, in whom biopsy demonstrated demyelinating lesions compatible with acute MS lesions. In 1 patient, recently started on highly active antiretroviral therapy, MS-like disease could represent an immune reconstitution syndrome. The lesions were reversible in 2 patients, but rapidly fatal in the third patient. These cases show that an MS-like disease may present in advanced HIV infection as focal monophasic leukoencephalopathy with either a reversible or fulminating course, mimicking progressive multifocal leukoencephalopathy.     

Multinodular polymyositis in a patient with human immunodeficiency and hepatitis C virus coinfection

We report a patient who developed multiple inflammatory muscle masses and generalized polymyositis in the setting of combined human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Magnetic resonance imaging (MRI) of muscles showed patchy edema which was particularly intense within the nodular masses. Polymerase chain reaction (PCR) showed no evidence of either virus within muscle. This report reviews earlier literature on muscle nodules associated with myositis and discusses the differential diagnosis of muscle masses in HIV infection.     

Non-progressive viral myelitis in X-linked agammaglobulinemia

We report a 14-year-old boy with X-linked agammaglobulinemia (XLA) complicated by isolated non-progressive myelitis caused by Coxsackie virus B1. Despite the absence of immunoglobulin supplement and persistence of the virus for the initial 2 years, motor impairment did not show any progression for 3 years. This report shows that the prognosis of central nervous system infection in XLA is not determined by immunoglobulin levels alone, and that it is not always progressive or fatal. The balance between host immunity and the virulence of the causative virus may be involved in the prognosis of meningoencephalitis in XLA.     

Acquisition of human immunodeficiency virus infection in a patient with multiple sclerosis: could these conditions positively influence each other’s course?

Journal of NeuroVirology - Patients with human immunodeficiency virus (HIV) infection have a decreased risk of developing multiple sclerosis (MS) and MS patients very rarely contract HIV infection....     

Multiple sclerosis and human T-cell lymphotropic retroviruses: negative serological results in 135 German patients

Summary A total of 135 sera and 18 cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) were screened for antibodies to human T-cell lymphotropic virus type I(HTLV-I) and human immunodeficiency virus (HIV) by ELISA tests. None of the sera or CSF reacted with HIV antigens. Only 3 out of 135 MS sera but no MS CSF showed increased reactions in the ELISA test for HTLV-I. However, these positive reactions were classified as non-specific by immunoprecipitation. Thus no serological evidence for infection with HIV, HTLV-I, or a related retrovirus was found in the MS patients.     

Epstein-Barr virus and multiple sclerosis

Epstein-Barr virus (EBV) is one of the most common and successful human viruses, infecting more than 90% of the world’s adult population. Despite its strong tumorigenic potential, most virus carriers remain healthy due to maintenance of a delicate balance between the host’s immune system, which limits production of virus particles, and the virus, which persists for the duration of the host’s life. New data show that this balance is altered on a subtle level in patients with multiple sclerosis (MS) and other autoimmune diseases who show enhanced as well as less restricted T-cell and antibody responses to EBV-encoded antigens. Such quantitatively and qualitatively distinct immune responses and the virus’ unique ability to immortalize B cells as well as to continuously stimulate strong T-cell responses during persistent infection suggest a possible role for EBV in the initiation and progression of symptomatic autoimmunity. We hypothesize that EBV promotes both autoimmune B and T-cell responses. EBV gene products might stimulate cross-reactive autoimmune B cells directly or increase their survival after infection. In addition, autoimmune T cells could be maintained via molecular mimicry between autoantigens and EBV antigens, and via the Th1 polarizing cytokine milieu of protective antiviral T-cell immunity. A better understanding of how EBV and EBV-specific immune control mechanisms interfere with the evolution of autoimmunity may generate a rationale for novel EBV-targeting therapeutic strategies aimed at the prevention and more efficient treatment of autoimmune diseases.     

Mononeuritis multiplex associated with cryoglobulinemia in HIV infection.

We describe a patient with human immunodeficiency virus (HIV) infection who developed mononeuritis multiplex associated with polyclonal (type III) cryoglobulinemia. The patient's symptoms stabilized following treatment with plasmapheresis and removal of the cryoglobulin. Our case represents the first report of polyclonal cryoglobulinemia in HIV disease and suggests that cryoglobulinemia may play an etiologic role in some patients with HIV-associated neuropathy.     

Natalizumab and HSV meningitis

Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is a monoclonal antibody approved for use in patients with relapsing multiple sclerosis (MS) as well as moderate to severe Crohn’s disease. We report the first case of a patient with a history of MS, on monthly natalizumab, who developed HSV-2 meningitis. We discuss the mechanism of action of natalizumab and review what is known about the reactivation of herpes infection in association with this medication. The question of herpes simplex virus (HSV) and varicella zoster virus (VZV) prophylaxis for patients is raised.     

Abnormal vitamin B12 metabolism in human immunodeficiency virus infection. Association with neurological dysfunction.

An increased prevalence of vitamin B12 deficiency has been reported in patients infected by the human immunodeficiency virus (HIV). We report an unexpectedly high prevalence (20%) of such abnormal vitamin B12 metabolism in a population of HIV-infected patients referred for neurological evaluation. This abnormality was associated with both peripheral neuropathy and myelopathy. A majority of those treated with cyanocobalamin had a therapeutic response. Selected neuropathological results suggest a relationship between vitamin B12 deficiency and vacuolar myelopathy. Vitamin B12 deficiency may be a frequent and treatable cause of neurological dysfunction in patients with HIV infection.     

Productive simian virus 40 infection of neurons in immunosuppressed Rhesus monkeys

There currently is no animal model of JC virus-associated progressive multifocal leukoencephalopathy (PML). Reactivation of simian virus 40 (SV40) in immunosuppressed rhesus monkeys, however, rarely causes a PML-like illness. We sought to isolate a neurotropic clone of SV40 and determine its pathogenic potential in monkeys. The clone SV40CNS1 was amplified by polymerase chain reaction from the brain DNA of a simian/human immunodeficiency virus-infected monkey that had developed PML and meningoencephalitis. Compared with the SV40 prototype 776, SV40CNS1 had a small number of single-amino-acid mutations and caused a productive infection in monkey fibroblasts. It was inoculated into 2 SV40-negative, simian/human immunodeficiency virus-immunosuppressed monkeys. Both animals developed meningoencephalitis with productive SV40 infection of cerebral cortical neurons and glia in the superficial layers of the cortex and at the gray-white junction. Focal SV40-infected cells were also found in the cerebellar molecular and granule cell layers and white matter. Both animals also developed disseminated SV40 infection with nephritis and pneumonitis. Thus, SV40CNS1 is infectious and pathogenic in immunosuppressed monkeys, but it induces encephalitis with fulminant productive infection in cortical neurons and systemic disease, rather than PML. These findings shed new light on SV40 neurotropism and expand the host cell range of this virus.     

Progressive tumefactive inflammatory central nervous system demyelinating disease in an acquired immunodeficiency syndrome patient treated with highly active antiretroviral therapy

We report here a case of progressive tumefactive inflammatory central nervous system (CNS) demyelinating disease in a human immunodeficiency virus (HIV)-seropositive patient treated with highly active antiretroviral therapy (HAART). Biopsy revealed diffuse macrophage and perivascular T-lymphocytic infiltrates with severe demyelination and relative axonal sparing. The disease progressed in a centrifugal fashion, to involve bihemispheric cerebral white matter, with subsequent central necrotic changes and atrophy. Treatment with HAART was discontinued, and inflammatory disease was treated with subcutaneous interferon (IFN)β-1a. Massive brain edema was controlled with courses of intravenous corticosteroids. Following fulminant monophasic disease, the patient stabilized with no evidence of disease progression over long-term follow up. We propose that immune response reconstituted by HAART can unmask an autoimmune response in susceptible individuals, analogous to the enhanced immune response to the preexisting acquired immunodeficiency syndrome (AIDS) opportunistic infections. Therapeutic options are considered.     

Rapidly progressive encephalopathy caused by Coxsackie meningoencephalitis in an elderly male

Enteroviruses and Coxsackie viruses are common causes of aseptic meningitis and encephalitis in children. These infections usually have a benign, self-limited course. However, they can have a florid presentation in immunocompromised patients, such as neonates, patients exposed to immunosuppressive drugs, such as transplant recipients and patients with agammaglobulinemia. We present a rare case of rapidly progressive acute encephalopathy caused by Coxsackie meningoencephalitis and complicated by refractory status epilepticus in an immunocompetent adult male. Our case highlights the importance of having a broad differential in patients presenting with rapidly progressive acute encephalopathy. Although rare, an enterovirus infection caused by a Coxsackie virus subtype can have a severe presentation causing significant morbidity. This case, also underscores the importance of searching for underlying immunodeficiency in malignant presentations of common viral infections. Hence, rapidly progressive acute encephalopathy due to coxsackievirus can occur in immunocompetent individuals. Aggressive and systematic diagnostic and therapeutic approach in such severe cases can influence overall outcomes.     

Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis

OBJECTIVE: The diagnosis of multiple sclerosis (MS) can be challenging because of the lack of a specific diagnostic test. Recent advances in proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. METHODS: We analyzed cerebrospinal fluid (CSF) samples from 29 patients with MS or clinically isolated syndromes (CIS), 27 patients with transverse myelitis (TM), 50 patients with human immunodeficiency virus (HIV) infection, and 27 patients with other neurological diseases (ONDs) by surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy. RESULTS: We found a unique protein of 12.5 kDa that was 100% specific for MS/CIS compared with TM or OND. Low levels of this protein were found in some patients with HIV infection. Tandem mass spectroscopy of a tryptic digest of this 12.5 kDa protein identified it as a cleavage product of full-length cystatin C (13.4 kDa), an important inhibitor of cysteine proteases including the cathepsins. Although total cystatin C levels in the MS patients was not different compared with controls, the patients with the highest 12.5/13.4 peak ratios also had the greatest cathepsin B inhibitory activity. INTERPRETATION: This suggests that cleavage of cystatin C may be an adaptive host response and may identify a subgroup of patients with MS.     

Parkinsonism in HIV dementia

Summary. A great number of human immunodeficiency virus (HIV)-infected patients develop a central nervous system disorder, commonly called HIV dementia or AIDS dementia complex (ADC). HIV dementia is independent of opportunistic infections and is due to the virus itself. Symptoms include psychomotor slowing, apathy and motor disorders similar tothe bradykinesia and postural and gait abnormalities observed in late Parkinson's disease. Consequently, HIV has been discussed during the last few years as an additional cause for parkinsonism, and parkinsonian syndromes as manifestations of HIV dementia. Moreover, the early phase of HIV infection gains increasing interest because of studies which report subtle neurological symptoms at this stage. Accordingly, we found in SIV-infected monkeys that dopamine is reduced by 44% within as few as two months of infection, indicating that changes during early infection must be thoroughly evaluated. In this short review, we discuss alterations in the nigrostriatal dopaminergic system during early and late immunodeficiency virus infection and the common clinical and biochemical features shared by HIV dementia and Parkinson's disease. Received January 15, 2002; accepted January 24, 2002     

Subacute meningoencephalitis associated with human T-lymphotrophic virus Type I (HTLV-I) Report of a case

We present a case of subacute meningoencephalitis associated with human T-lymphotrophic virus Type I (HTLV-I) infection, for HTLV-I antibody being positive in serum and cerebrospinal fluid. Necropsy findings disclosed leptomeningeal and parenchymal mononuclear cell infiltration with multinucleate giant cells, which are similar to those seen in subacute encephalitis with acquired immunodeficiency syndrome (AIDS).     

Skeletal muscle involvement in human immunodeficiency virus infection: a report of four cases

Human immunodeficiency virus (HIV) may affect any part of the neuraxis and may affect skeletal muscle in many ways, ranging from myofiber atrophy in the wasting syndrome to inflammatory muscle disease and a host of opportunistic infections involving muscle. We report here a case series of 4 zidovudine-naοve patients with proven HIV infection with myopathy. One was a case of HIV wasting syndrome, and the three others were diagnosed as HIV polymyositis. Muscle biopsy proved invaluable in the characterization of these cases.     

Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis

Although most children with human immunodeficiency virus (HIV) infection have neurological dysfunction, in childhood the incidence of symptomatic cerebrovascular disease is low. Cerebral aneurysmal arteriopathy in childhood AIDS has been reported in the past and considered to have a relatively long latency following the primary infection. We report a 1 month-old infant with congenitally acquired HIV infection, and herpes encephalitis; she presented a sudden cardiorespiratory arrest followed by coma and was found to have a giant saccular aneurysm of the left basilar artery. Literature review showed that cerebral aneurysmal artheriopathy is an unusual manifestation in newborns and infants and this case is possibly the youngest patient reported with aneurysma, herpes encephalitis and AIDS. The role of HIV and herpes simplex infections in the pathogenesis of this lesion is discussed.     

The peripheral nerve complications of human immunodeficiency virus (HIV) infection

Peripheral nerve complications occurring in patients with human immunodeficiency virus (HIV) infection are frequent and challenging. This review discusses these various complications according to the degree of advancement of HIV disease. Particular emphasis is placed upon emerging causes of neuropathy found in the context of HIV disease, such as infection with hepatitis C and human T-lymphotropic virus type I, as well as neuropathies related to antiretroviral medications.     

A rare cause of cerebral venous thrombosis: cryptococcal meningoencephalitis

Cryptococcal meningoencephalitis (CM) is a serious central nervous system infection caused by Cryptococcus neoformans, seen mostly in immunocompromised hosts and less in immunocompetent patients. The vast majority of cryptococcosis cases are seen as human immunodeficiency virus infections with advanced immunosuppression. Meningitis and meningoencephalitis are the most common clinical manifestations. Nevertheless, immunocompetent patients with CM are rarely reported. Cerebral venous sinus thrombosis is a rare complication of CM. Here, we report an immunocompetent patient with CM from a non-endemic area, who presented with an acute onset and atypical symptoms associated with cerebral venous thrombosis.     

Adaptation of antiretroviral therapy in human immunodeficiency virus infection with central nervous system involvement

The authors describe a patient with known human immunodeficiency virus (HIV)-1 infection who presented with two generalized seizures and was found to have extensive white matter disease and a left/bilateral temporo-occipital focal slowing on electroencephalography (EEG). There were no magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) indications for opportunistic infection. Plasma viremia was controlled, whereas viral replication was uncontrolled in CSF. CSF-specific genotype-guided adaptation of the antiretroviral therapy in order to optimize central nervous system (CNS) penetration resulted in clinical improvement and normalization of MRI and EEG. Our case report illustrates the importance of individualized antiretroviral therapy in HIV infected patients with neurological complications.