Nagagopal Venna

Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection.

Objective: To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations. Methods: Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification. Results: Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8+ T cells, especially effector CD8+ T cells. Conclusions: These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8+ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus–host interactions involved in CNS functional deficits.

Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy

ABSTRACT JC virus (JCV)-specific CD8+ cytotoxic T lymphocytes (CTL) are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine the frequency and phenotype in fresh blood of CD8+ T cells specific for two A*0201-restricted JCV epitopes, VP1p36 and VP1p100, and assess their impact on JC and BK viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with PML (HIV+ PML patients) classified as survivors. After magnetic preenrichment of CD8+ T cells, epitope-specific cells ranged from 0.001% to 0.22% by tetramer staining, with no significant difference among the three study groups. By use of seven-color flow cytometry, there was no predominant differentiation phenotype subset among JCV-specific CD8+ T cells in healthy individuals, HIV+ subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the acute phase, there was a majority of activated effector memory cells. BKV DNA was undetectable in all blood samples by quantitative PCR, while a low JC viral load was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV DNA were detected in 33.3% and 13.3% of all urine samples, respectively, independent of the presence of JCV-specific CTL. The detection of JCV DNA in the urine was associated with the presence of a JCV VP1p100 CTL response. Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML.

Neurosyphilis presenting with gummatous oculomotor nerve palsy

Although epidemiological studies suggest that the incidence of primary syphilis is rising,1 neurosyphilis remains an uncommon manifestation of Treponema pallidum infection. In addition, the MRI appearances of this treatable neurological condition are not well known. Many patients with neurosyphilis are asymptomatic, but manifestations include subacute basal meningitis, a meningovascular syndrome of small deep cerebral and cranial nerve infarctions, chronic gummatous inflammation with focal intracranial mass lesions, chronic comportmental dementia of general paresis, and chronic sensory-ataxic myelopathy of tabes dorsalis. We report a case in which a meningeal form of neurosyphilis presented with rapid evolution of a pupil-involving oculomotor nerve palsy to highlight the clinical, CSF, and MRI features and good response to treatment. The patient was a 54 year old right handed homosexual man with a history of syphilis of unknown stage, treated with penicillin 25 years previously. He was well until 6 weeks prior to evaluation when he sustained minor head trauma in an automobile accident, followed by intermittent headaches, fatigue, photophobia, and anorexia. Four days before …

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.

Reversible dementia in a patient with central nervous system escape of human immunodeficiency virus

HIV-associated neurocognitive disorders (HAND) are a group of conditions ranging from asymptomatic neurocognitive impairment to disabling dementia. The clinical spectrum and pathogenesis of these disorders is changing in the era of highly active antiretroviral therapy (HAART). High levels of HIV may exist in the cerebrospinal fluid (CSF) of some patients despite suppression of serum viral loads by HAART. We report a case of a 51-year-old male with profound levels of HIV in the CSF despite low serum levels. Adjusting his HAART regimen based on HIV genotype susceptibility data and a CNS Penetrating Effectiveness (CPE) score resulted in a dramatic improvement in cognitive function. Progressive dementia in this context is a rare but emerging trend and may be reversible.

Temporal arteritis-like presentation of carotid atherosclerosis.

A 68 year-old woman presented with a two-week history of amaurosis fugax, ipsilateral fronto-temporal headache and jaw claudication suggesting carotid giant cell arteritis. However, this syndrome proved to be due to atherosclerosis causing complete occlusion of the external carotid artery at its origin and narrowing of the internal carotid artery. Combined external and internal carotid endarterectomy relieved the symptoms. The symptom complex of temporal arteritis may be rarely mimicked by carotid atherosclerotic occlusive disease.

Laboratory investigation of fungal infections of the central nervous system.

While fungal infections of the central nervous system (CNS) are relatively rare, fungal pathogens are increasingly being recognized as an important etiology of CNS infections, particularly amongst the growing immunocompromized population. In this paper we aim to provide a practical approach to the diagnosis of fungal infections of the CNS, review some of the diagnostic methods currently available and discuss diagnosis of certain pathogens of particular interest to the practicing neurologist.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α. Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location. Conclusions: Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments. Classification of evidence: This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection

Acute encephalitis, encephalopathy, and seizures are known rare neurologic sequelae of respiratory tract infection with seasonal influenza A and B virus, but the neurological complications of the pandemic 2009 swine influenza A (H1N1) virus, particularly in adults, are ill-defined. We document two young adults suffering from H1N1-associated acute respiratory distress syndrome and renal failure who developed cerebral edema. The patients acutely developed a transtentorial brain herniation syndrome including a unilateral third nerve palsy (dilated and unresponsive pupils), elevated intracranial pressure, coma, and radiological evidence of diffuse cerebral edema. In both patients, neurological deterioration occurred in the context of hyponatremia and a systemic inflammatory state. These patients illustrate that severe neurologic complications, including malignant cerebral edema, can occur in adults infected with H1N1 virus, and illustrate the need for close neurological monitoring of potential neurological morbidities in future pandemics.

Clinical features, diagnostic findings, and treatment of Susac syndrome: A case series

BACKGROUND Susac syndrome (SS) is a rare, presumed autoimmune condition characterized by the clinical triad of branch retinal artery occlusions (BRAOs), encephalopathy, and sensorineural hearing loss. The aim of this study was to evaluate clinical features, diagnostic results, treatment, and outcomes in SS. METHODS Five patients with SS were referred to three tertiary care centers in Boston. The observation period across these patients was 7-57months. RESULTS At initial presentation, none of the patients demonstrated the complete triad of BRAO, sensorineural hearing loss, and encephalopathy. The interval between symptom onset and diagnosis of SS was 4-30weeks. Brain MRI findings thought to be characteristic of SS (including callosal fluid-attenuated inversion recovery (FLAIR) hyperintense and T1 hypointense lesions) were frequently absent. Microinfarcts noted on diffusion-weighted imaging (DWI), BRAOs and vessel wall hyperfluorescence on fluorescein angiography (FA) were present in all cases in the acute encephalopathic phase. All patients treated with glucocorticoids and intravenous immunoglobulins (IVIg) alone experienced further clinical progression until additional immunosuppressive therapy was instituted. CONCLUSIONS The rarity of SS, its incomplete and variable presentation, and the nonspecific imaging findings invariably led to delayed diagnosis. DWI and FA should be used to identify the acute microvascular injury and monitor treatment response. Immunomodulatory agents more potent than glucocorticoids and IVIg might be required to control the disease.