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Biomedical subjects

Joseph R Berger

Publications and source records attributed to Joseph R Berger.

At least 19 recordsLinked to original sources
PubMed2006

Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab.

The dramatic increase in the incidence of progressive multifocal leukoencephalopathy (PML) that occurred as a consequence of the AIDS pandemic and the recent association of PML with the administration of natalizumab, a monoclonal antibody to alpha4 integrin that blocks inflammatory cell entry into the brain, has stimulated a great deal of interest in this previously obscure viral demyelinating disease. The etiology of this disorder is JC virus (JCV), a polyoma virus, observed in 80% of the population worldwide. Seroepidemiological studies indicate that infection with this virus typically occurs before the age of 20 years. No primary illness owing to JCV infection has been recognized and the means of spread from person to person remains obscure. Following infection, the virus becomes latent in bone marrow, spleen, tonsils and other tissues. Periodically the virus reactivates during which time it can be demonstrated in circulating peripheral lymphocytes. The latter is significantly more commonly observed in immunosuppressed populations than that in normal subjects. Despite the large pool of people infected with JCV, PML remains a relatively rare disease. It is seldom observed in the absence of an underlying predisposing illness, typically one that results in impaired cellular immunity. A variety of factors are likely responsible for the unique increase in frequency of PML in HIV infection relative to other underling immunosuppressive disorders. Preliminary data suggests that natalizumab appears to distinctively predispose recipients to PML relative to other infectious complications. Studies in these populations will be invaluable in understanding the mechanisms of disease pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain.

Ziconotide intrathecal infusion was recently approved by the United States Food and Drug Administration for the treatment of intractable severe chronic pain. Patients with neuropathic pain make up a significant population among those who experience chronic pain for which there are less than optimal pharmacotherapeutic options. Published clinical trials provide a global view of ziconotide efficacy and safety. A subset of patients in clinical trials obtained complete pain relief, a remarkable finding given the history of drug treatment for neuropathic pain. To provide more information regarding those who respond to ziconotide therapy, we discuss three patients with neuropathic pain who received ziconotide infusion. Two patients with longstanding neuropathic pain, one with complex regional pain syndrome (formerly known as reflex sympathetic dystrophy) of the leg and one with lumbar radiculitis, achieved temporary but complete pain relief from single 5- and 10-microg epidural test doses. In the third case, a patient with longstanding bilateral leg and foot neuropathic pain from acquired immunodeficiency syndrome and antiretroviral drug therapy achieved considerable pain relief from a long-term continuous intrathecal infusion. The patients who received a single dose had mild central nervous system adverse effects such as sedation, somnolence, nausea, headache, and lightheadedness. The patient who received the intrathecal infusion experienced mild-to-severe adverse effects depending on the rate of infusion; these effects included sedation, confusion, memory impairment, slurred speech, and double vision. This patient could sense impending adverse effects and made rate adjustments or suspended infusion to avert untoward symptoms. In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion.

Analgesics, Non-Narcotic↗
PubMed2005

ALS syndrome in patients with HIV-1 infection.

BACKGROUND: A viral etiology of amyotrophic lateral sclerosis (ALS) has been proposed because of the selective vulnerability of motor neurons to certain viruses. During the last 20 years, at least 19 cases of ALS or ALS-like disease have been reported in HIV-1 (HIV) seropositive individuals. OBJECTIVE: To describe two cases of clinically definite ALS in patients with HIV infection and to review the previously reported cases of HIV-associated ALS syndrome. SETTING: A multidisciplinary ALS center and Neuro-AIDS clinic at a tertiary care university hospital. PATIENTS/DESIGN: We investigated and prospectively monitored two patients who had developed clinically definite ALS by El Escorial criteria several years after acquiring the HIV infection. The previously reported cases of ALS or ALS-like disease in patients with HIV infection were reviewed for comparison and contrast with the characteristics of sporadic ALS. RESULTS: The clinical course of ALS in our two HIV seropositive individuals mirrored that of classical sporadic ALS. A review of previously described 19 patients with ALS syndrome revealed clinically definite ALS in 4 cases and clinically probable or possible ALS in 15. ALS commenced at different stages of the HIV disease; in 7 patients, HIV infection was discovered contemporaneously with diagnosis of ALS. CD4+ T cell count ranged from 2 to 560 cells/mm3. Three (1 definite ALS) of the fatal cases were studied at autopsy and all exhibited pathology outside the motor neuron pool. Unlike our patients, 7 of 8 patients with HIV-associated ALS syndrome receiving HAART demonstrated at least partial recovery of their motor deficit. CONCLUSIONS: ALS-like syndrome can occur in association with HIV infection; however, the causal relationship remains uncertain. Patients with ALS syndrome related to HIV infection are generally younger in age and often demonstrate pathology outside the motor neuron system. Patients with HIV-associated ALS syndrome may improve following antiretroviral therapy. An aggressive HAART regimen to reduce viral load should be pursued in all such cases.

Adult↗
PubMed2005

Intravascular lymphomatosis presenting with sudden hearing loss.

Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation of malignant large cell lymphoma cells in small vessels. Neurological manifestations are typically the initial and, often the only, clinically obvious consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem demonstration of the intravascular tumor. We report a patient in whom sudden hearing loss heralded IVL and propose that the hearing loss may have been the consequence of labyrinthine infarction consequent to the aggregation of malignant cells in the internal auditory artery.

Anti-Inflammatory Agents↗
PubMed2005

Brachial amyotrophic diplegia in a patient with human immunodeficiency virus infection: widening the spectrum of motor neuron diseases occurring with the human immunodeficiency virus.

Although amyotrophic lateral sclerosis and progressive spinal muscular atrophy have been recognized to occur in association with human immunodeficiency virus infection, to our knowledge, brachial amyotrophic diplegia, a form of segmental motor neuron disease, has not been previously reported. Brachial amyotrophic diplegia results in severe lower motor neuron weakness and atrophy of the upper extremities in the absence of bulbar or lower extremity involvement, pyramidal features, bowel and bladder incontinence, and sensory loss. We describe a human immunodeficiency virus-seropositive man without severe immunosuppression or prior AIDS-defining illnesses who had brachial amyotrophic diplegia. This disorder may represent one end of a spectrum of motor neuron diseases occurring with this retrovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Cerebrospinal fluid proteomics and human immunodeficiency virus dementia: preliminary observations.

Protein profiling using mass spectrometry may be useful in identifying previously unknown protein markers in human immunodeficiency virus (HIV) dementia and provide insight into disease pathogenesis. Six samples of matched cerebrospinal (CSF) and blood serum from patients with no, mild, and moderate dementia were prepped for biomarker screening by the Ciphergen system. Chips were analyzed in the matrix-assisted laser desorption/ionization (MALDI) mass spectrometer at low mass (700 to 20,000 Da) and at higher mass (5000 to 100,000 Da). In both serum and CSF samples, differences in protein intensity appeared to correlate with degree of dementia. This preliminary study suggests that protein markers of HIV dementia may be detected by MALDI mass spectrometry.

AIDS Dementia Complex↗
PubMed2004

The blood brain barrier in HIV infection.

The blood brain barrier (BBB) serves as a protective mechanism for the brain. It prevents entry of pernicious substances, whether chemical or cellular, from free access to the CNS. In essence, it is a defense mechanism preserving the internal milieu of the brain. The BBB may be disrupted by a number of pathological processes. CNS infection is a well recognized cause of BBB disruption. Among the CNS infections demonstrated to affect the BBB is human immunodeficiency virus (HIV). HIV infects the brain shortly after its acquisition. Studies of cerebrospinal fluid (CSF) as well as dynamic studies of contrast enhanced magnetic resonance imaging have confirmed abnormalities of the BBB in HIV-infected persons. Pathological studies of the CNS have confirmed the in vivo studies, and in vitro studies have identified a range of pathogenic mechanisms of HIV-associated BBB compromise. This disruption of the BBB may not only contribute to accelerating brain infection by HIV, but may also alter CNS function. Additionally, BBB disruption has implications with respect to antiretroviral therapy. This review will address these issues.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Identification of potential antibody markers in HIV-associated dementia.

Markers for HIV-associated dementia (HAD) are needed for diagnosis and management. Specific antibodies to brain and immune complexes (IC) in the cerebrospinal fluid (CSF) are potential markers. CSF IC were found in 4 of 4 HAD patients, 2 of 2 AIDS-central nervous system (CNS) lymphoma patients with dementia, 0 of 1 AIDS-CNS lymphoma patient without dementia, 0 of 1 AIDS-CNS toxoplasmosis patient without dementia, and 0 of 10 neurologic disease controls. By blinded immunoblots, antibrain antibodies in serum and CSF were found in 11 of 12 HAD cases and 7 of 19 HIV-1 patients without HAD. All 11 non-HIV-1 controls were negative. These and published data suggest antibrain antibodies and IC may serve as markers of HAD.

AIDS Dementia Complex↗
PubMed2004

Neuroimaging correlates of HIV-associated BBB compromise.

The mechanisms underlying blood-brain barrier (BBB) compromise in human immunodeficiency virus (HIV) infection and the ways in which BBB compromise might impair neurocognitive function remain poorly understood. This study had two aims: (1) to examine the relationship between BBB breakdown, measured using contrast-enhanced magnetic resonance imaging (CE-MRI), plasma viral load, and neurological status; and (2) to examine the influence of highly active antiretroviral therapy (HAART) on the relationship between neuroinflammation using myoinositol/creatine (mI/Cr), a surrogate marker of glial activation as measured by magnetic resonance spectroscopy (MRS), and BBB compromise determined by CE-MRI. In 25 HIV-infected patients, we found that: (1) the severity of neurocognitive impairment correlated with the degree of BBB breakdown in the basal ganglia; (2) for any given degree of BBB compromise, patients with high plasma viral load were more severely impaired; (3) BBB compromise correlated with mI/Cr in the basal ganglia; and (4) for any given level of mI/Cr, the severity of BBB compromise and the severity of neurocognitive impairment were significantly less in patients on HAART than in those who were HAART-naive. These results confirm a role for BBB compromise in the pathogenesis of HIV-associated neurocognitive impairment and suggest that elevated plasma viral load in the presence of BBB compromise may increase the risk for development of HIV-associated dementia (HAD). Additionally, they suggest a salutary effect of HAART on the incidence and severity of HAD, which may, in part, be due to protection of BBB integrity.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Inflammatory changes and breakdown of microvascular integrity in early human immunodeficiency virus dementia.

Increased postcontrast enhancement in contrast-enhanced magnetic resonance imaging (CE-MRI) of the central nervous system (CNS) is a predictor of human immunodeficiency virus (HIV) dementia severity in HIV-infected subjects. The present study confirms this earlier finding in a mildly impaired patient cohort, and demonstrates that the increased postcontrast enhancement is correlated with increased cerebrospinal fluid (CSF) levels of monocyte chemoattractant protein (MCP)-1, an inflammatory chemokine, and increased CNS levels of mI, a microglial marker. These results suggest that early CNS inflammation may underlie the microvascular changes observed, and may be a factor in the development of HIV dementia.

AIDS Dementia Complex↗