L. Ambrosone

Cognitive impairment in systemic lupus erythematosus: a follow-up study

Abstract We evaluated outcome and the clinical value of cognitive impairment in systemic lupus erythematosus (SLE). Fifty-one consecutive SLE subjects with or without overt nervous system involvement received two comprehensive neuropsychiatric and neuropsychological assessments, including the Mental Deterioration Battery, the Mini Mental State Examination (MMSE), and tests from the Wechsler Adult Intelligence Scale. The two neuropsychological assessments were made when subjects were in stable neurological condition. Twenty-seven patients were found to have neuropsychiatric symptoms (NP-SLE) at the first assessment, and three others developed them during the follow-up. Fifteen patients (10 NP-SLE) had cognitive impairment at the first assessment. At retest the cognitive deficit persisted in all patients but one (non-NP-SLE) and had developed in four others. In the cognitively impaired subjects scores on MMSE approached the cutoff for an overt dementing condition. No progressively decreasing scores were found on any of the tests. No relationships were shown between neuropsychological diagnosis and neuropsychiatric disorder, neuroradiological findings, disease activity, or steroid and nonsteroid immunosuppressive therapy. Cognitive impairment thus seems to be a stable symptom of CNS involvement in SLE. It corresponds to the subjective complaint of intellectual difficulties and marginal performance on the MMSE. Intellectual deterioration may occur in patients without other symptoms of NP-SLE. Standardized neuropsychological testing methods should be used routinely to assess SLE patients.

A vascular Osteonecrosis in Patients with SLE: Relation to Corticosteroid Therapy and Anticardiolipin Antibodies

Sixty-nine unselected SLE patients were studied to evaluate the prevalence of avascular osteonecrosis (AVN) and its relationship with steroid therapy and with anticardiolipin antibodies (aCL). All the patients were under treatment with corticosteroids. AVN occurred in seven of the 69 patients (10. 14%) and was not related to corticosteroid intake. Seventeen of the 69 patients were also treated with methylprednisolone pulse therapy (MPPT) and cumulated the highest corticosteroid doses but none of them suffered from AVN. Excluding the 17 MPPT-treated SLE patients, corticosteroid intake was significantly higher in the AVN-SLE patients. Abnormal IgG and/or IgM aCL serum levels were found in two of the seven AVN-SLE patients and in 24 of the 62 non-AVN SLE, without a statistically significant difference. None of the seven AVN-SLE patients showed features of antiphospholipid syndrome. We conclude that in SLE patients a continuous high-dose steroid treatment may be considered a risk factor for AVN. On the contrary, MPPT regimen may reduce this risk. Anticardiolipin antibodies might represent an added factor which could play a role in some patients but not in all.

Viral RNA in nerve tissues of patients with hepatitis C infection and peripheral neuropathy.

To assess the presence of viral ribonucleic acid (RNA) in nerve tissues of 15 patients with hepatitis C virus (HCV) infection and peripheral neuropathy with (11) or without (4) mixed cryoglobulinemia, nested reverse transcription–polymerase chain reaction (RT‐PCR) was performed. Amplification of HCV‐RNA was successful in 7 patients with and 3 without mixed cryoglobulinemia. This study demonstrates that the nested RT‐PCR technique is a sensitive method to detect viral RNA in nerve tissue, and offers further evidence that in patients with HCV infection peripheral neuropathy can occur in the absence of mixed cryoglobulinemia. Muscle Nerve 27:102–104, 2003

Peripheral neuropathy in hepatitis-related mixed cryoglobulinemia: electrophysiologic follow-up study.

A retrospective study was performed on 27 patients with hepatitis C (HCV)–related mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis, peripheral neuropathy) to assess peripheral nerve involvement during follow‐up of up to 8 years. All patients had the same degree of organ/system involvement initially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon‐α2b (rIFN‐α2b). At first examination, neurological signs and electrodiagnostic findings consistent with peripheral neuropathy were found in 20 (74%) and in 24 (88.8%) patients, respectively. Neurological evaluation and electrodiagnostic data at 3 and 8 years revealed worsening of neuropathy, whereas the other manifestations of mixed cryoglobulinemia (MC) were stable. At the last examination, clinical and electrodiagnostic signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 patients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3 (25%) of the patients treated with prednisone alone and in 6 (40%) of the patients additionally treated with rIFN‐α2b. Our data confirm that in patients with HCV‐related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN‐α2b to steroid treatment. Muscle Nerve, 2005

Autonomic neuropathy in mixed cryoglobulinemia

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-α2b (RIfn-α2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-α2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-α2b to steroid treatment.

Increased serum concentrations of soluble HLA-class I antigens in hepatitis C virus related mixed cryoglobulinaemia

OBJECTIVE To investigate whether quantitative alterations of both β2microglobulin (β2μ) associated HLA class I heavy chains (sHLA-I) and β2 μ free class I heavy chains (sHLA-FHC) in sera of patients with hepatitis C virus (HCV) infection occur and whether they distinguish patients with mixed cryoglobulinaemia (MC). METHODS 83 HCV infected patients were studied and divided into three groups: (A) without cryoglobulinaemia (n=21), (B) with polyclonal MC (n=20), (C) with monoclonal MC (n=42). Serum sHLA-I and sHLA-FHC were measured by double determinant radioimmunoassay using monoclonal antibodies: TP25.99 as catching antibody, and NAMB-1 and HC-10 as revealing antibodies. Western blot identified HLA-I isoforms. RESULTS The serum concentrations of sHLA-I and of sHLA-FHC in HCV infected patients versus controls were respectively 1.3(0.5) μg/ml (mean (SD)) versus 0.8 (0.3) (p<0.001) and 13.9 (7.1) ng/ml versus 9.2 (5) (p<0.001). sHLA-I were 1.01 (0.4) μg/ml in group A, 1.04 (0.4) μg/ml in group B, and 1.47 (0.4) μg/ml in group C (p=0.001). Statistical analysis showed a significant difference versus controls for groups B (p<0.02) and C (p<0.001). sHLA-FHC were 12.8 (8.3) ng/ml in group A, 17.2 (7.1) ng/ml in group B, and 12.9 (6.2) ng/ml in group C (p<0.02). A significant difference versus controls for each group was found (p<0.02, p<0.001, and p<0.02, respectively). Different patterns of sHLA-I isoforms were observed. CONCLUSIONS Increased serum concentrations of sHLA-I and sHLA-FHC characterise HCV infected patients. The highest sHLA-I concentrations seem to distinguish patients with monoclonal MC. In this last condition sHLA could play a part in the HCV escape and in B cell proliferation. The significance of sHLA-FHC is still undefined.