Melike Mutlu

Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome.

Increased cerebrospinal fluid (CSF) IL-6 has been reported in patients with Behçets disease (BD) and neurological involvement. To elucidate the value of IL-6 as a marker of disease activity, serum and CSF IL-6 levels of 68 BD patients with acute (26) or chronic progressive (14) parenchymal involvement (pNB), dural sinus thrombosis (10), ischemic stroke (5) or headache (13) were measured by ELISA. Samples from multiple sclerosis, subacute sclerosing panencephalitis, and noninflammatory neurological disorders were used as controls. CSF but not serum samples of neuro-BD patients with acute pNB displayed significantly increased IL-6 levels as compared to other groups. Chronic progressive pNB patients also showed increased CSF IL-6 levels, albeit less prominent. Patients with increased CSF IL-6 levels were more likely to have increased CSF cell counts and total protein levels and these three parameters were correlated with long-term (3 years) disease outcome. In four chronic progressive patients, IL-6 was elevated despite otherwise normal CSF. CSF IL-6 seems to be a marker of disease activity and long-term outcome for pNB along with CSF cell count and protein levels. CSF IL-6 could be used in chronic progressive patients who have normal CSF cell, or protein levels to detect disease activity.

Enhanced IL-6 Production in Aquaporin-4 Antibody Positive Neuromyelitis Optica Patients

ABSTRACT Anti-aquaporin-4 (Aqp-4) antibody and complement system have emerged as major pathogenic factors in neuromyelitis optica (NMO). To test the significance of interleukin-6 (IL-6), another important humoral immunity factor, in NMO pathogenesis, we measured serum and cerebrospinal fluid (CSF) IL-6 levels of 23 NMO, 11 transverse myelitis, 16 optic neuritis, 27 relapsing remitting multiple sclerosis patients, and 20 neurologically normal controls. NMO and transverse myelitis patients had higher serum and CSF IL-6 levels than other groups. Particularly, anti-Aqp-4 positive NMO patients (n == 12) had higher serum/CSF IL-6 levels than anti-Aqp-4 negative patients (n == 11) and CSF IL-6 levels correlated with anti-Aqp-4 levels and disease severity of the NMO patients. Our results suggest that IL-6 is involved in NMO pathogenesis presumably via anti-Aqp-4 associated mechanisms.

Cognitive Impairment in Neuro-Behcet's Disease and Multiple Sclerosis: A Comparative Study

Both multiple sclerosis (MS) and neuro-Behcets disease (NBD) can cause a cognitive dysfunction mainly involving the executive functions. We conducted this study to clarify the probable differential cognitive/behavioral profiles of MS and NBD. Twenty consecutive cases with parenchymal NBD (13 male, seven female), and 20 cases with MS (five male, 15 female) were evaluated. Both groups had a thorough neurological examination; an evaluation for Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Becks Depression Scale; and a detailed neuropsychological evaluation masked to the diagnosis. Among the two groups, male/female ratio differed significantly while other demographic and clinical features were not different. In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcets cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcets cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcets patients have a more severe “frontal”-executive dysfunction than MS patients.

Primary cerebral lymphoma with a 5-year remission to single-agent corticosteroids

Primary central nervous system lymphoma (PCNSL) constitutes 1–3% of adult-onset intracranial tumors and less than 1% of extranodal non-Hodgkin lymphomas (NHL). PCNSL’s incidence is higher in the elderly population and the average age of diagnosis is 60 years. Although PCNSL has a poor prognosis, it may occasionally undergo spontaneous remissions without chemotherapy [1–3]. A 61-year-old woman presented with a left-sided brachiofacial hemiparesis. Her brain magnetic resonance imaging (MRI) revealed a right frontoparietal mass lesion measuring 4 cm6 7 cm in dimensions. There was partial contrast enhancement most prominently on the posterior side of the lesion [Figure 1(A)]. Complete blood count and routine serum biochemistry tests (including serum B12, folate levels and thyroid function tests) were normal and the serological screening for vasculitis and autoimmune diseases (anti-nuclear antibody (ANA), antiDNA, anti-extractable nuclear antigen (ENA) screen, anti-neutrophil cytoplasmic antibody (ANCA), anti-cardiolipin antibodies, lupus anticoagulant, anti-thyroid antibodies), syphilis, and HIV yielded negative results. Cerebrospinal fluid examination was normal with no oligloclonal bands. Stereotactic brain biopsy showed reactive gliosis and therefore tumor-like demyelinating disease was considered as the foremost diagnosis and the patient was put on high-dose methylprednisolone (MP) (1000 mg iv for 10 days plus oral tapering) treatment. The lesion showed a remarkable response to high-dose steroid treatment. Following this steroid regimen, the clinical findings completely disappeared in 1 month, the mass lesion considerably regressed and the contrast enhancement vanished [Figure 1(B)]. As she did not have any prior neurological complaints, her first episode was considered as clinically isolated syndrome and the patient was followed without any additional treatment with annual radiological followup. She continued in a stable clinical condition in the subsequent years. Five years after her first neurological episode, she presented with ataxia and left homonymous hemianopia. Her repeat MRI examination revealed new right occipital [Figure 1(C)] and right cerebellar contrast enhancing lesions. Her symptoms regressed minimally after a trial of high-dose MP treatment. In the following months, under high-dose i.v. and oral MP treatment, her clinical findings deteriorated and the lesion enlarged. An 18-fluorodeoxyglucose positron emission tomography (PET) examination showed hypermetabolism in the right occipital lobe and in the right cerebellar hemisphere [Figure 1(D)]. In the repeat stereotactic brain biopsy, the lesion was found out to be a diffuse large B-cell NHL. PCNSL is one of rare but quite malignant neoplasms of the CNS. In different studies, 5-year survival rates have been reported to be between 5% and 40% and without appropriate treatment, the average survival time might be less than 3 months