Asli Kurne

Immunological patterns identifying disease course and evolution in multiple sclerosis patients.

Reliable, and easy to measure, immunological markers able to denote disease characteristics in multiple sclerosis (MS) patients are still lacking. We applied a multivariate statistical analysis on results obtained by measuring-by real-time RT-PCR-mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS patients. The combined measurement of mRNA levels of IL-1beta, TNF-alpha, TGF-beta, CCL20 and CCR3 was able to distinguish MS patients from healthy individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary progressive MS patients while TNF-alpha, IL-10, CXCL10 and CCR3 differentiate relapsing MS patients. Our results indicate that multi-parametric analysis of mRNA levels of immunological relevant molecules in PBMCs may represent a successful strategy for the identification of putative peripheral markers of disease state and disease activity in MS patients.

Effect of interferon β-1a on serum matrix metalloproteinase—9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in relapsing remitting multiple sclerosis patients

Abstract.There is emerging evidence that matrix metalloproteinases (MMPs) might be involved in blood brain barrier (BBB) breakdown in multiple sclerosis.A group of natural tissue inhibitors of metalloproteinases (TIMPS) regulates proteolytic activity to prevent tissue damage. TIMP-1 and MMP-9 are known to be secreted as heterodimers and TIMP-1 preferentially functions to inhibit MMP-9 activity. In this present study, the effects of IFNβ-1a on serum MMP-9 and TIMP-1 were evaluated longitudinally during a one-year period. The MMP-9 levels showed no significant changes while TIMP-1 levels gradually and significantly increased during 3rd and 6th months of therapy compared with pretreatment levels.

Assessment of citrullinated myelin by 1H-MR spectroscopy in early-onset multiple sclerosis.

BACKGROUND AND PURPOSE: Myelin instability and citrullinated myelin basic protein have been demonstrated in the brains of patients with chronic and fulminating forms of multiple sclerosis (MS). Our aim was to trace citrulline in the brains of patients with early-onset MS by using proton MR spectroscopy (1H-MR spectroscopy). MATERIALS AND METHODS: A short-echo single-voxel 1H-MR spectroscopy by using the point-resolved proton spectroscopy sequence was performed in 27 patients with MS and 23 healthy subjects. Voxels of interest were chronic demyelinating lesions (CDLs, n = 25) and normal-appearing white matter (NAWM, n = 25) on T2-weighted imaging, and when available in patients with MS, enhancing demyelinating lesions (EDLs, n = 8). Frontal white matter (WM) was studied in control subjects. N-acetylaspartate, choline, and myo-inositol (mIns)-creatine (Cr) ratios and the presence of a citrulline peak were noted. RESULTS: Citrulline peaks were more frequently observed in patients with MS than in control subjects (P = .035), located in the NAWM in 8/25 (32%), in CDLs in 7/25 (28%), and in EDLs of 1/8 (12.5%) patients with MS. The presence of citrulline and measured metabolite/Cr ratios was not related to age at imaging, age at disease onset, duration of disease, or number of relapses. There was no significant metabolic difference between the NAWM of patients with MS and the WM of the control subjects. mIns/Cr was significantly greater in CDLs compared with the NAWM of patients with MS and the WM of healthy subjects. CONCLUSIONS: Citrulline was more frequently identified in the brains of patients with early-onset MS than in healthy subjects by 1H-MR spectroscopy, suggesting an association of increased citrullination of myelin proteins with demyelinating diseases.

A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a safer profile and additional anti-inflammatory and immuno-modulatory properties compared to parent compounds. Preventive treatment of experimental autoimmune encephalomyelitis (EAE)-induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55-with the NO-releasing derivative of flurbiprofen HCT1026 delayed disease onset and significantly decreased disease severity. HCT1026 treatment was associated to (i) decreased mRNA levels of pro-inflammatory cytokines, caspase-1, and iNOS in blood cells; (ii) decreased ability of encephalitogenic T cells to proliferate; (iii) reduced number of central nervous system (CNS)-infiltrating T cells; (iv) decreased axonal loss and demyelination; (v) increased CD4(+) CD69(-) CD25(+) regulatory T cells in the spleen.

Testicular teratoma and anti-N-methyl-D-aspartate receptor-associated encephalitis

We report a patient with a testicular teratoma and seminoma, who developed treatment-responsive encephalitis associated with antibodies to NMDA receptor, but not antibodies to Ma2 protein. A 30-year-old male was admitted to hospital with a 1-week history of personality changes, confusion, agitation and recurrent generalised tonic-clonic seizures. His past medical history was unremarkable, except for the presence of generalised fatigue and sore throat a few days before symptom onset. On physical examination, the only pathological finding was bilateral testicular enlargement. He was agitated and disoriented to time, place and person; his speech was incoherent, and he had persecutory and erotic delusions. The rest of the neurological examination was normal. The initial laboratory studies, including complete blood count, biochemistry, EEG and brain MRI, were normal. The CSF examination was significant for an elevated protein concentration (113 mg/dl) with normal glucose content and mild leukocytosis (25 cells/μl); bacterial and viral studies, including PCR for herpes simplex virus, were negative. Testicular ultrasound revealed the presence of a left testicular mass and right testicular torsion. Computerised tomography of the chest, abdomen and pelvis demonstrated the presence of a retroperitoneal lesion, which was suggestive of metastasis. These findings led us to consider the diagnosis of paraneoplastic encephalitis. Accordingly, CSF …

Familial Mediterranean fever and central nervous system involvement: a case series.

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 ± 11.8 years, mean age at first FMF symptom was 12.6 ± 5.6 years, and mean age at neurologic involvement was 25.8 ± 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 ± 8.9 years in the demyelinating group, and 23.4 ± 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 ± 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF. Abbreviations: BAEP = brainstem auditory evoked potentials, CNS= central nervous system, CSF = cerebrospinal fluid, EEG = electroencephalography, ESR = erythrocyte sedimentation rate, FMF= familial Mediterranean fever, HSP = Henoch-Schönlein purpura, IL = interleukin, MEFV = the FMF gene, MRI = magnetic resonance imaging, PAN= polyarteritis nodosa, PRES = posterior reversible leukoencephalopathy syndrome, SEP = somatosensorial evoked potential, VEP= visual evoked potential.

An unusual central nervous system involvement in rheumatoid arthritis: combination of pachymeningitis and cerebral vasculitis

Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.

Spontaneous unilateral accessory nerve palsy: a case report and review of the literature

Isolated spinal accessory nerve (SAN) palsy is a well-recognized complication of surgical prodecures in the posterior triangle of the neck. Various rare etiological factors were also described. Whatever the etiology, the typical clinical features of SAN palsy can be listed as atrophy/weakness of the trapezius muscle and moderate winging of the scapula. It is imperative to promptly diagnose this condition in the early stage to avoid long-term impairment and to have a better functional outcome. Herein, we present a patient with a diagnosis of spontaneous spinal accessory nerve palsy, which was rarely reported in the relevant literature.

Aphasic status epilepticus with periodic lateralized epileptiform discharges in a bilingual patient as a presenting sign of “AIDS–toxoplasmosis complex”

We describe an HIV-infected, bilingual patient presenting with Wernickes aphasia due to partial status epilepticus with periodic lateralized epileptiform discharges, as the first sign of AIDS-toxoplasmosis complex. The localization of the native and secondary language centers in the brain and the possible role of recurrent seizures in the fluctuating course of Wernickes aphasia in this patient are discussed. The clinical course of this patient supports the belief that a second language area for a second language learned in the later stages of life is located in an area different from that for the native language but still in close proximity to it.

A clinically isolated syndrome: a challenging entity: multiple sclerosis or collagen tissue disorders: clues for differentiation.

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations of a number of diseases such as multiple sclerosis (MS) and collageneous tissue disorders. In the present study, particular systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were followed up with the initial diagnosis of possible MS with no evidence of collagen tissue disorders for several years, are described. Five patients with the final diagnosis of SLE and five pSS patients are evaluated with their neurologic, systemic and radiologic findings.Over several years, all developed some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes unexpected in MS. During the regular and close follow-up laboratory evaluations of vasculitic markers revealed positivity, leading to the final definite diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS, a relapsing remitting clinical profile, or lack of response to the regular MS treatment should be evaluated for the presence of a connective tissue disease. Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies profile, markers, cranial and spinal magnetic resonance imaging, can be helpful for the differential diagnosis. Lack of response to the regular multiple sclerosis treatment, even increasing rate of relapses can force the clinician for the differential diagnosis. In particular cases an accurate diagnosis can only be made after close follow-up.