Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus.

INTRODUCTION: Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies revealed the strong association between serum anti-Sm and organic brain syndrome, consisting mainly of acute confusional state (ACS) of diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). However, the precise mechanism by which anti-Sm causes diffuse NPSLE remains unclear. Of note, recent studies demonstrated that anti-U1 RNP antibodies (anti-RNP) in cerebrospinal fluid (CSF) are associated with NPSLE. The present study was designed to explore the association of anti-Sm antibodies in CSF with NPSLE. METHODS: Paired serum and CSF specimens were obtained from 72 patients with NPSLE (49 with diffuse NPSLE, 23 with neurological syndromes or peripheral neuropathy (focal NPSLE) and from 22 control patients with non-SLE neurological diseases. Sera were also obtained from 41 patients with active SLE without neuropsychiatric manifestations (non-NPSLE). Anti-Sm and anti-RNP were measured by enzyme-linked immunosorbent assay (ELISA). Blood-brain barrier (BBB) function and intrathecal anti-Sm production were evaluated by Q albumin and CSF anti-Sm index, respectively. Binding of anti-Sm to neuroblastoma cell lines SK-N-MC and Neuro2a was examined by flow cytometry and by cell ELISA. RESULTS: Anti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE control. CSF anti-Sm, but not CSF anti-RNP, was significantly elevated in ACS compared with non-ACS diffuse NPSLE or with focal NPSLE. By contrast, there were no significant differences in serum anti-Sm or anti-RNP among subsets of NPSLE and non-NPSLE. Whereas there were no significant differences in CSF anti-Sm index, Q albumin was elevated in ACS compared with non-ACS or with focal NPSLE. Notably, CSF anti-Sm was correlated with Q albumin (r = 0.2373, P = 0.0447) or with serum anti-Sm (r = 0.7185, P <0.0001) in 72 patients with NPSLE. Finally, monoclonal anti-Sm and purified human anti-Sm bound to the surface of SK-N-MC and Neuro2a. CONCLUSIONS: These results demonstrate that the elevation of CSF anti-Sm through transudation from systemic circulation due to damaged BBB plays a critical role in the pathogenesis of ACS. More importantly, the data indicate that anti-Sm is yet another autoantibody with presumed neural toxicity, but might not be the last.

Unusual amnesia in a patient with VGKC-Ab limbic encephalitis: a case study.

We describe the case of a patient with confirmed voltage-gated potassium channel antibody-associated encephalitis (VGKC-Ab). MRI studies revealed bilateral hyper-intensity in the hippocampi, with their volumes preserved. At presentation, the patient's anterograde and retrograde memory skills were found to be impaired and he showed fluctuation in his ability to recall familiar information. Following treatment with immunotherapy, his condition improved considerably and, in a series of follow up assessments, he performed satisfactorily (i.e., within the average range or above) on formal tests of memory, as well as on a range of other cognitive tests, including tests of executive function. By contrast, in the context of contemporaneous unstructured interviews, he showed a strong tendency to confabulate. We argue that the reported case broadens the phenomenology of VGKC-Ab limbic encephalitis and raises important theoretical questions about the aetiology of this patient's most unusual memory disorder.

Flow cytometric assessment of anti-neuronal antibodies in central nervous system involvement of systemic lupus erythematosus and other autoimmune diseases.

The objective of this study is to evaluate the association between anti-neuronal antibody (anti-NA) and central nervous system (CNS) manifestations of systemic lupus erythematosus (SLE) and other rheumatic diseases using a flow cytometric method. Anti-NA was measured by flow cytometry in serum and cerebrospinal fluid (CSF) samples from patients with SLE (n=44 for serum, n=17 for CSF), other rheumatic diseases (n=64 for serum, n=21 for CSF) and from healthy controls (n=65 for serum, n=18 for CSF). Serum anti-NA was more frequently observed in SLE (31.8%, 14/44) than in other rheumatic diseases (4.7%, 3/64, P<0.001) or in healthy controls (0%, 0/65, P<0.00001). In SLE patients, the frequency of serum anti-NA was significantly higher in CNS-SLE (76.5%, 13/17) than in non CNS-SLE (3.7%, 1/27, P<0.000001). CSF anti-NA was detected in 88.2% (15/17) of CNS-SLE and was more frequently detected in CNS-SLE (15/17, 88.2%) than in other rheumatic diseases with CNS involvement (1/21, 4.8%, P<0.000001) or in healthy controls (0/18, P<0.000001). In conclusion, serum anti-NA was more frequently found in CNS-SLE than in non CNS-SLE, other rheumatic diseases or in healthy controls. The frequency of CSF anti-NA in CNS-SLE was significantly higher than in other rheumatic diseases with CNS involvement or in healthy controls.

Psychiatric presentation of voltage-gated potassium channel antibody-associated encephalopathy. Case report.

Voltage-gated potassium channel antibody encephalopathy, a rare cause of limbic encephalopathy, typically presents with memory impairment and seizures. Psychiatric symptoms have not been emphasised in the literature. Here we describe a 58-year-old man who presented with panic attacks and psychogenic non-epileptic seizures and, later on, developed delusions and hallucinations and then confusion. He was found to have antibodies to voltage-gated potassium channels. Treatment with immuno-modulatory therapy resulted in almost complete recovery.

Postoperative interleukin-6 and cortisol concentrations in elderly patients with postoperative confusion.

OBJECTIVE: To investigate changes in plasma interleukin (IL)-6, cortisol or noradrenaline concentrations after surgery in elderly patients with postoperative confusion. METHODS: We studied 80 patients aged 70-90 years undergoing abdominal surgery and measured plasma IL-6, cortisol or noradrenaline concentrations before surgery, at the end of surgery, and 24 and 48 h after surgery. RESULTS: Plasma IL-6 concentrations in elderly patients with postoperative confusion were 83.2 +/- 30.5, 49.3 +/- 14.1 and 42.9 +/- 19.4 pg.ml(-1) at the end of surgery, and 24 and 48 h after surgery, respectively, being significantly higher than in elderly patients without postoperative confusion (58.0 +/- 37.5, 36.1 +/- 20.0 and 28.2 +/- 16.7 pg.ml(-1)). Plasma cortisol concentrations in elderly patients with postoperative confusion (42.2 +/- 7.8, 38.3 +/- 8.3 and 33.1 +/- 8.4 microg.dl(-1) at the end of surgery, and 24 and 48 h after surgery, respectively) were significantly higher than in elderly patients without postoperative confusion (32.9 +/- 6.7, 30.4 +/- 8.6 and 25.6 +/- 6.5 microg.dl(-1), respectively). There were no significant differences in plasma norepinephrine concentrations at all sampling points between elderly patients with and without postoperative confusion. However, plasma IL-6 and cortisol concentrations were related in elderly patients with postoperative confusion (at the end of surgery and 24 and 48 h after surgery). However, there was no relationship between plasma IL-6 and cortisol concentrations 24 and 48 h after surgery in elderly patients without postoperative confusion. CONCLUSION: Elderly patients with postoperative confusion had increased plasma IL-6 and cortisol concentrations. The interaction between IL-6 and cortisol after surgery is associated with developing postoperative confusion in the elderly patients.