Bilateral eighth cranial nerve neuropathy in human immunodeficiency virus infection.

A 21-year-old HIV-1 seropositive African man developed an acute febrile illness followed by a sudden sensorineural bilateral hearing loss. Neurophysiological studies demonstrated the bilateral involvement of both branches of the vestibulocochlear cranial nerves. Immunological studies revealed the presence of an ongoing central nervous system HIV-1 infection. A sural nerve biopsy showed the presence of inflammatory cells. We suggest HIV testing for all cases of sudden onset of bilateral hypoacusia.

Autoantibodies to glutamic acid decarboxylase (GAD) detected by an immuno-trapping enzyme activity assay: relation to insulin-dependent diabetes mellitus and islet cell antibodies.

It has recently been proposed that the islet 64,000 Mr protein autoantigen (64K) of insulin-dependent diabetes mellitus (IDDM) is glutamic acid decarboxylase (GAD). We evaluated, by means of a newly developed immunotrapping enzyme activity assay (ITEAA), the prevalence of circulating GAD-autoantibodies (Ab) in a large population of IDDM patients (n = 168), blood donors (n = 87) and non-diabetic autoimmune patients (n = 40). The latter two groups were used as controls. Overall, GAD-Ab were found in 22% of IDDM patients, but in none of the two control groups (P = 0.007). These specificities were invariably associated with islet cell antibodies (ICA) (31.6% in IDDM with ICA vs 0 in IDDM without ICA, P = 0.0001), and this prevalence was higher in sera with high titer ICA (54.5% in IDDM with ICA greater than 80 JDF-units vs 22.6% of IDDM with ICA 5-80 JDF units; P = 0.002). Moreover, GAD-Ab were associated with the female sex (P = 0.002) and the concomitant presence of thyroid and/or gastric antibodies (P = 0.002). No correlation was observed between GAD-Ab and age of the patients, duration of IDDM, or associated non-organ specific antibodies. Our study indicates that GAD-Ab measured by ITEAA are: (1) detected in a proportion of IDDM patients; (2) strongly associated with ICA; (3) preferentially found in IDDM female patients with autoimmune polyendocrine serology; and (4) detected with lower frequency than that reported for 64K-Ab in IDDM.

Kappa light chain predominance in serum and cerebrospinal fluid from human immunodeficiency virus type 1 (HIV-1)-infected patients.

We measured kappa/lambda light chain ratios of Ig and IgG in 41 serum and 34 cerebrospinal fluid (CSF) samples from 47 patients at different clinical stages of human immunodeficiency virus type 1 (HIV-1) infection and in serum and CSF samples from control subjects. Both ratios were more elevated in HIV-1 seropositive subjects than controls. The elevation was more evident in samples from asymptomatic seropositive patients (ASP) than those from patients with acquired immunodeficiency syndrome (AIDS). In addition, there was a statistically significant elevation of Ig kappa/lambda ratios in ASP CSF compared to serum. We also delineated the light chain composition of oligoclonal IgG bands (OCB) by isoelectric focusing followed by immunofixation in CSF and serum samples from selected ASP and patients with AIDS who had neurological involvement. Five of six AIDS and all seven ASP samples had IgG OCB exclusively or predominantly of the kappa type. Four IgG OCB of the lambda type and one free lambda chain band were seen in CSF from a pediatric AIDS patient. The presence of an abnormally elevated kappa/lambda ratio correlated with the presence of IgG kappa OCB (p less than 0.02). We conclude that HIV-1 infection is associated with a kappa light chain predominance and with OCB mainly composed of kappa light chains.

CSF oligoclonal banding pattern changes in a long-surviving SSPE patient treated with alpha-IFN.

Oligoclonal bands are a constant, non-modifiable feature of CSF examination in SSPE. We studied CSF oligoclonal IgG banding pattern in a long-surviving SSPE patient treated with serial courses of intrathecal alpha-IFN. alpha-IFN administration did not significantly modify the clinical status of the patient. Oligoclonal IgG banding pattern varied during the 58 month-long treatment. Oligoclonal bands disappeared at the end of the first course only to reappear during the third course, 2 years later, with a different electrophoretic pattern. We conclude that oligoclonal bands may transiently disappear from the CSF of long-surviving SSPE patients. Although alpha-IFN treatment induces no clinical improvement, it might affect the quality of Ig production.

Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement.

To assess the role of alpha-tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha-tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C-1 (20) of the Centers for Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha-tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30 cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C-1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoelectric focusing herpes simplex virus-gB overlay study in brainstem encephalitis.

We report a case of herpetic brainstem encephalitis (HBE) retrospectively diagnosed in adult patient. Conventional immunovirological studies failed to disclose the etiology of this patient's affection. An isoelectric focusing-antigen overlay (IEF-O) technique showed that the target of one of the four cerebrospinal fluid oligoclonal bands was herpes simplex virus (HSV)-1 glycoprotein B, indicating a specific anti-HSV immunoresponse restricted to the CNS. IEF-O may represent a useful support for in vivo diagnosis of HBE.

Antibody against EBV in CSF from HIV-1 and HTLV-I infected patients.

We have measured the levels of antibody (ab) against different Epstein-Barr virus (EBV) antigens in 10 AIDS patients, 7 HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and 20 control subjects. We found comparable serum levels of anti-EBV ab between AIDS patients, HAM/TSP patients and control subjects. By contrast, anti-EBV ab were present in the large majority of CSF from AIDS patients (70%) and HAM/TSP patients (60%) but only in 15% of control group. Our results support a synergistic role of EBV in retroviral infections of the central nervous system.

Immunological study in newborns at risk for HIV-1 infection.

We have performed an isoelectric focusing study (IEF) to detect the presence of oligoclonal bands (OB) in serum and in 5 of the correspondent cerebrospinal fluid (CSF) from 14 HIV-seropositive mothers and their newborns. CB were also searched in serum from 4 newborns every 3 months over a period of 12 months. OB were present in 8/14 sera and in 3/3 CSF obtained from the mothers; CSF OB were different from the correspondent serum indicating an intrathecal synthesis. OB were also visualized in serum, but not in CSF, from 3 newborns studied at birth: two of them died respectively at 4 and 5 months of age. One of the 4 newborns that were serially studied showed the appearance of OB at 12 months of age. A comparative study between sera obtained at the moment of delivery from the mother and her newborn showed that oligoclonal banding patterns were superimposable. Our data indicated that: 1) the IgG forming OB in the newborn's serum derive from a passive filtration from mother's serum; 2) the presence of OB seems to be an unfavourable prognostic feature in infants at risk for HIV-1 infection.

Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis.

We measured levels of alpha-tumor necrosis factor (alpha-TNF) in cerebrospinal fluid and serum samples from 50 drug-free patients with multiple sclerosis, 25 patients with other neurological diseases, 27 patients with non-neurological diseases, and 10 normal subjects. The most elevated levels of alpha-TNF were found in patients with inflammatory or autoimmune diseases. Comparable serum levels of alpha-TNF were detected in normal control subjects, patients with multiple sclerosis, and patients with degenerative neurological diseases. In patients with multiple sclerosis, alpha-TNF levels were also unrelated to time elapsed between the occurrence of clinical exacerbation and the time of sample collection. Only 3 patients with chronic progressive multiple sclerosis had detectable alpha-TNF in the cerebrospinal fluid. Our data do not support a role for elevated levels of circulating alpha-TNF in the maintenance of the disease. However, we cannot rule out the possibility that a transient elevation of alpha-TNF triggers the cellular events leading to demyelination in multiple sclerosis.