Focal Central Nervous System Disease Research Articles

DEHYDRATION ENCEPHALOPATHY: A NEUROLOGICAL EMERGENCY IN THE OLDER ADULTS

DEHYDRATION ENCEPHALOPATHY: A NEUROLOGICAL EMERGENCY IN THE OLDER ADULTS

Primary systemic Sjögren syndrome (SS) preceding systemic lupus erythematosus: a retrospective study of 4 cases in a cohort of 55 SS patients

That SS and SLE can coexist is well established. The time relationship between the two diseases is however not well known. To determine whether SS can precede SLE, we reviewed the charts of 55 patients with SS diagnosed in our department between 1975 and 1985. All 55 patients fulfilled at least four of the six preliminary criteria for SS developed by the European Study Group for SS. At entry, none met four ARA criteria for SLE and none had anti-double-stranded DNA or anti-Sm antibodies. The mean follow-up was 12 years (range 8-18 years). Four of the 55 patients developed SLE (7.5%). High titres of anti-native DNA antibodies (> 35 IU RIA, normal < 7 IU) appeared in four patients (2-11 years after the diagnosis of SS). Two of these patients fulfilled at least four ARA criteria for SLE; two others had only three criteria. Two additional patients developed anti-Sm antibodies without anti-native DNA antibodies 1 and 10 years after the initial diagnosis of SS, respectively. Both patients fulfilled six ARA criteria for SLE. At entry, anti-SSA and/or anti-SSB antibodies were present in all six SS patients and persisted subsequently. The main clinical events suggesting progression to SLE were pleuropericarditis, glomerulonephritis and focal central nervous system disease. In conclusion, SS with extraglandular components can antedate SLE by many years. Anti-native-DNA and anti-Sm antibodies should be measured when atypical clinical manifestations occur in a patient with systemic SS.

Neurofibromatosis Type 1 (Recklinghausen's Disease)

Neurologic and cognitive function in neurofibromatosis type 1 (NF1) were assessed in a controlled pilot study of 13 pairs of siblings aged 6 to 27 years. One subject in each pair was affected with NF1, and the other, the control subject, was unaffected. Subjects with evidence of focal central nervous system disease were excluded. The 13 subjects with NF1 had no excess of mental retardation, attention-deficit disorder, or specific learning disorders (using Wilcoxon's Signed Rank Test and McNemar's Test for Symmetry). These subjects, however, had significantly higher scores for subtle neurologic abnormalities (21 vs 6) and significantly lower full-scale IQ scores (94 vs 105) than their unaffected siblings. The IQ scores of the affected subjects were not clustered at the lower end of the scale but showed a slight downward shift in distribution compared with those of their siblings. In addition, a visual-spatial orientation deficit was present in eight of nine affected subjects so evaluated. The findings suggest that subjects with NF1 have a widespread alteration of the brain during development that manifests as one or more specific types of neuropsychologic deficits.

Serum complement activation in central nervous system disease in sjögren's syndrome

Central nervous system disease and vasculitis are extraglandular manifestations of Sjögren's syndrome. In our experience, central nervous system disease develops in approximately 70 percent of patients with Sjögren's syndrome and biopsy documented peripheral vasculitis. In order to further investigate the pathogenesis of central nervous system disease and its relationship to peripheral vasculitis in Sjögren's syndrome, we examined sera of patients with Sjögren's syndrome with and without focal central nervous system involvement for evidence of terminal complement pathway activation. Patients were classified as having active focal central nervous system involvement only when they had focal neurologic deficits on physical examination, plus at least one abnormal neurodiagnostic test result. Two thirds of these patients also had cognitive or psychiatric dysfunction. Patients were classified as having peripheral vasculitis if they had clinical and histopathologic documentation of vascular inflammation. Serum SC5b-9 was measured by a sensitive enzyme-linked immunoabsorbent assay. Total hemolytic complement assay, measurement of serum C3 and C4 by radial immunodiffusion, and determination of immune complexes were performed. Fluid-phase terminal complement complexes (SC5b-9) were detected in the sera of 25 of 30 (83 percent) patients with focal central nervous system involvement, but in only seven of 21 (33 percent) patients with Sjögren's syndrome without focal central nervous system disease (p = 0.00084 by Yates' chi-square analysis). Four of these seven patients without focal central nervous system disease, but who had serum SC5b-9, had psychiatric or cognitive dysfunction. SC5b-9 was also detected in sera from 14 of 15 (93 percent) patients with active biopsy-documented peripheral vasculitis in contrast to 18 of 36 (50 percent) patients without clinical evidence of peripheral vasculitis (p = 0.0094). Serum SC5b-9 was a more sensitive indicator of complement activation than circulating immune complex or complement assays. These findings suggest that terminal complement activation may participate in the pathophysiology of both central nervous system and peripheral vasculitis in Sjögren's syndrome. Serum SC5b-9 appears to be a useful diagnostic indicator of vascular inflammation in Sjögren's syndrome and appears to identify those patients at risk for central nervous system complications.

Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement of primary Sjogren's syndrome or systemic lupus erythematosus.

We have examined cerebrospinal fluid (CSF) and serum from patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) for evidence of activation of the terminal pathway of complement. Fluid phase terminal complement complexes (SC5b-9), quantitated by ELISA, were detected in the CSF of 14 of 16 patients with SS and focal central nervous system (CNS) disease. Five of six SS patients without focal CNS disease but with psychiatric disease or cognitive dysfunction had detectable CSF SC5b-9, whereas two other SS patients without focal CNS or neuropsychiatric disease had no detectable CSF SC5b-9. Six of seven patients with SLE or SLE overlap syndrome with CNS involvement had CSF SC5b-9, whereas two patients with SLE without CNS involvement had no CSF SC5b-9. A subset of SS and SLE patients with CNS disease had SC5b-9 detected in CSF but not in serum. SC5b-9 was generally absent from the CSF of patients with noninflammatory CNS diseases. These findings demonstrate intrathecal activation of terminal complement in patients with CNS SS or CNS SLE, and suggest a role for terminal complement activation in the pathophysiology of CNS involvement in both SS and SLE.

Organic Mental Changes With Fluorouracil Therapy

To the Editor.— Two patients showed a rapid and dramatic change in their mental status within a few weeks to two months of the start of weekly intravenous fluorouracil chemotherapy for colon cancer with liver metastases. The first patient was a 70-year-old man who after two months of fluorouracil therapy had no evidence of focal central nervous system disease but was confused and had marked psychomotor retardation and slight lethargy. Brain scan was normal, while the electroencephalogram showed diffuse slow wave activity. The second patient was an 80-year-old widowed woman who was mildly depressed but had no impairment of mental ability when admitted to the hospital. After three weekly doses of fluorouracil intravenously, mild confusion was noted, which progressed to semicoma. Findings of neurologic examination were normal except for a severely confused mental state characterized by total disorientation as to time and place as well as by inappropriate answers to

Circadian variation of the plasma 17-hydroxycorticosteroids in central nervous system disease.

The pattern of the circadian variation of the plasma 17-OHCS was studied in 48 patients with focal disease of the central nervous system unassociated with disturbance of consciousness. Disease of the temporal lobe, pretectum or hypothalamus was present in 27 patients (Group A). Pituitary disease characterized by sellar enlargement, but with minimal evidence of endocrinopathy, was present in 13 patients (Group B). The control group consisted of 21 patients with focal central nervous system disease outside these areas (Group C), and 47 normal subjects (Group D). The circadian patterns of the patient groups were compared to those of the normal subjects with respect to 3 criteria: (a) slope of linear trend (calculated by the method of least squares); (b) extent of variation of plasma steroid levels from this fitted straight line; and (c) average plasma steroid levels. Patients in Group A differed significantly (at an over-all 5% level) from normal subjects with respect to the first 2 criteria. In patients in ...

ALDOSTERONE EXCRETION IN PRETECTAL DISEASE.

Interest in the possible central nervous system regulation of aldosterone secretion has been centered on a region including the pineal gland, the subcommissural organ and the superior colliculi. These parts of the nervous system adjoin the pretectal area and lesions of this area in humans are characterized by unique oculomotor abnormalities. We have studied basal urinary aldosterone levels and their response to sodium restriction in 7 patients with such lesions. Six subjects with focal central nervous system disease not involving the pretectal area served as controls and were similarly studied. All the control subjects showed the expected rise in urinary aldosterone following sodium restriction. In 4 of the 7 patients with pretectal disease such a rise failed to occur.