A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

Diagnostic value of detecting JC virus DNA in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy.

JC virus DNA was detected by PCR in the cerebrospinal fluid of 17 of 23 (73.9%) patients with confirmed cases of progressive multifocal leukoencephalopathy and 2 of 48 (4.2%) controls without progressive multifocal leukoencephalopathy. The sensitivity and specificity of this PCR were 74 and 95.8%, respectively, while the positive and negative predictive values were 89.5 and 88.5%, respectively.

HIV infection.

Drug use will soon become the major risk for transmission of HIV infection in the United States, which will result in near equal incidence of the disease in men and women and more affected children. This has serious implications for the health care community and for the community at large. Thus, it is necessary to pursue aggressively risk reduction strategies targeted for difficult-to-reach populations such as illicit drug users and commercial sex workers. This will involve a vigorous public health campaign to bring education messages about safer sex practices, safer injection techniques, and enhanced drug treatment services to these groups. Prevention strategies include consideration of needle exchange as a public policy for IDUs. There are appropriate concerns in the larger community that needle exchange might send a mixed message or promote drug use, but there is no scientific evidence to support this view. To the contrary, there is a growing body of evidence that suggests drug users change behavior in response to education messages and that clean needles may reduce disease risk. Currently, stable seroprevalence rates in some IDU populations suggest that education messages about injection practices are heeded. Unfortunately, sexual practices have not shown similar changes. Most, if not all, HIV-infected persons will experience neurologic complications during their illness, especially as improved medical therapy ameliorates systemic complications. The approach to diagnosis and management requires a thorough understanding of the diverse clinical syndromes that may occur and a systematized approach to investigation of the cause.

Progressive multifocal leukoencephalopathy in patients with human immunodeficiency virus.

Lesions of progressive multifocal leukoencephalopathy (PML) in patients infected with the human immunodeficiency virus (HIV) often have mononuclear cell infiltrates so intense that they obscure the nature of the lesion. This response may be especially prominent in stereotactic biopsies of contrast-enhancing areas. Of 10 consecutive PML lesions biopsied stereotactically, three were markedly, two were moderately, and five were mildly inflamed. There were few to no enlarged oligodendrocytic nuclei with inclusions in the markedly and moderately inflamed lesions. We investigated all biopsies with immunoperoxidase, DNA in situ hybridization, polymerase chain reaction, and Southern immunoblot methodologies for toxoplasmosis and the following viruses: JC, cytomegalovirus, herpes simplex viruses I and II, and human T-cell lymphotropic viruses I, II, and III. We confirmed the presence of JC virus in each lesion; polymerase chain reaction revealed HIV genome only in one. Inflammatory PML lesions in HIV+ patients do not reflect co-infection with toxoplasmosis or viruses commonly seen in these patients. The mononuclear cells are primarily T lymphocytes. Patients with severely inflamed PML lesions, whether HIV+ or not, often show stabilization of symptoms with or without antiviral treatment and have longer lengths of survival than patients with less inflamed lesions.

Disorders of peripheral nerves associated with HIV infection.

The clinician with interest in neuromuscular disease must become familiar with the clinical manifestations of HIV infection. It is important to realize that not everyone who is infected with HIV will develop clinical AIDS. This includes patients with clinical manifestations related to HIV infection, for example, neuropathy. Thus, if treatment is successful, patients can continue a normal life. HIV infection should be considered in almost any neuromuscular syndrome, especially neuropathies with features of demyelination, which may be the first manifestation of HIV infection. Plasmapheresis may be the treatment of choice for these disorders. Steroids should be used with caution. AZT seems to be a promising new agent to combat AIDS.

The neuromuscular manifestations of human immunodeficiency virus infections.

We studied 14 patients with neuromuscular disorders and concomitant infection with human immunodeficiency virus to define clinical syndromes and prognosis. Eight patients had painful sensorimotor peripheral neuropathy; two, chronic inflammatory demyelinating polyneuropathy; two, mononeuropathy or mononeuropathy multiplex; one, recurrent myoglobinuria; and one, chronic proximal weakness and elevated creatine kinase levels. All eight patients with painful neuropathy had overt symptoms of acquired immunodeficiency syndrome. Chronic inflammatory demyelinating polyneuropathy was the first manifestation of acquired immunodeficiency syndrome in both patients with this syndrome. Both died from overwhelming sepsis within six months of the neuropathy's onset. Patients with mononeuropathy multiplex had a variable course. Immunosuppressant medication had no effect in two patients.

A new complication of AIDS: thoracic myelitis caused by herpes simplex virus.

Progressive thoracic myelopathy occurred in a patient with AIDS. Concurrent opportunistic infections included disseminated systemic cytomegalovirus, aspergillosis, and cutaneous herpes simplex virus (HSV). At autopsy, immune stains indicated that the myelopathy was caused by HSV type 2 infection of the spinal cord.

Neurologic complications in acquired immunodeficiency syndrome (AIDS).

Neurologic syndromes in AIDS are of four types: infections, para-infections, neoplastic, and paraneoplastic. All levels of the neuraxis can be affected. Neurologic complications may be the initial symptom or the cause of death. Aggressive evaluation, including biopsy of cerebral lesions, is indicated because effective treatment can be given.