Hemodynamic evidence linking cognitive deficits in clinically isolated syndrome to regional brain inflammation.

BACKGROUND AND PURPOSE: To investigate the relation between hemodynamic measurements and memory function in patients with clinically isolated syndrome (CIS). METHODS: Forty CIS patients were administered tests of verbal short-term/working memory and passage learning. Using dynamic susceptibility contrast MRI cerebral blood volume (CBV), cerebral blood flow and mean transit time values were estimated in 20 cerebral regions of interest, placed in normal appearing white matter (NAWM) and normal appearing deep gray matter structures, bilaterally. RESULTS: CIS patients showed significantly impaired scores on working memory and secondary verbal memory that correlated inversely with elevated CBV values in the left frontal and periventricular NAWM, thalamus, right caudate and corpus callosum. CONCLUSIONS: Verbal memory in CIS correlates inversely with elevated CBV values of brain structures involved in memory. As these hemodynamic changes, detected in CIS, are indicative of inflammation, the observed cognitive disturbances may relate to widespread brain inflammatory processes that prevail in early multiple sclerosis.

Rising incidence of multiple sclerosis in females associated with urbanization.

OBJECTIVE: To design and perform a case-control study of multiple sclerosis (MS) in Crete, an island of 0.6 million people, that has experienced profound socioeconomic changes in recent decades. METHODS: All MS cases occurring on Crete from 1980 to 2008 were ascertained. To search for putative risk factors, a structured questionnaire of 71 variables was employed, with patients with MS (n = 657) being compared to random controls (n = 593) matched for age, gender, and current place of residence. RESULTS: MS incidence rose markedly on Crete over the past 3 decades. This increase was associated with a major shift in MS distribution among genders (1980: F/M = 0.9; 2008: F/M = 2.1), with females living in towns or having relocated at a young age from the countryside to urban centers being mainly affected. In rural Crete, MS showed lesser increases and gender preference. Of the major changes that accompanied urbanization, smoking among women with MS increased dramatically, while imported pasteurized cow milk virtually replaced fresh goat milk produced locally. Compared to controls, female patients with MS more often used contraceptives and were older at first childbirth. Besides smoking, alcohol drinking and vitamin intake was more common among female patients with MS. Also, the distribution of childhood diseases and chronic medical conditions differed significantly between patients with MS and controls. CONCLUSIONS: MS incidence rose markedly over 3 decades in a genetically stable population in tandem with a transition from rural to urban living, thus possibly implicating environmental factors introduced by urbanization.

Benign multiple sclerosis in Crete.

Our objective was to study multiple sclerosis on Crete, an island of 0.6 million inhabitants sharing a similar genetic background and the same environment. Case ascertainment was achieved using the MS Epidemiology Program Project of Crete. The diagnosis and classification of multiple sclerosis were made by established clinical and magnetic resonance imaging criteria, and disease evolution was assessed by periodic evaluations. Thorough clinical and laboratory evaluations were conducted; a detailed history, including a questionnaire of 36 items, was taken. Data obtained were analysed for possible interaction with disease prognosis. We identified 587 cases of multiple sclerosis (F:M = 1.6), >90% of which were of Cretan origin from both parental lines. Age at onset was 31.5 +/- 10.3 years (mean +/- SD) and disease duration 12.7 +/- 9.1 years. About 84.6% had relapsing remitting multiple sclerosis, 9.4% primary progressive multiple sclerosis and 6% clinically isolated syndrome. Nearly 40% of our multiple sclerosis patients with disease duration >10 years (mean = 16.2 +/- 5.3 years) remained with no or mild disability (Expanded Disability Status Scale [EDSS] < or =3). Also, about 30% of patients with relapsing remitting multiple sclerosis showed benign disease evolution (EDSS < or =3) more than 20 years (mean = 24.0 +/- 3.3) after onset. Factors predisposing to benign multiple sclerosis included younger age at onset, shorter disease duration and a lower number of relapses. We conclude that a substantial proportion of patients with multiple sclerosis from Crete follow a rather benign disease course, and this may relate to the genetic background of the population and/or to environmental factors.

Central nervous system involvement as the presenting manifestation of autoimmune rheumatic diseases: an observational study using the American College of Rheumatology nomenclature for neuropsychiatric lupus.

OBJECTIVE: We sought to describe CNS involvement as initial presentation of autoimmune rheumatic diseases using a standardized nomenclature. PATIENTS AND METHODS: A 6-year observational study (1999-2005) was conducted in the University Hospital of Heraklion Crete, a regional referral secondary/tertiary care academic center. Patients presenting with new neurological symptoms of acute/subacute onset underwent clinical and laboratory screening for systemic autoimmune disorders. The diagnosis of an autoimmune rheumatic disorder was based upon the American College of Rheumatology (ACR) classification criteria, whereas for primary antiphospholipid syndrome (PAPS) we used the Sapporo preliminary criteria. In order to describe the neurological syndromes we used the ACR nomenclature for neuropsychiatric lupus. RESULTS: During this period fourteen patients (ten females and four males) were recorded. Eight patients had systemic lupus erythematosus (SLE), four had primary APS and the remaining two had systemic vasculitis. Four out of the eight SLE patients had secondary APS. Two of them presented with movement disorder (chorea). The other two and all four patients with primary APS presented with cerebrovascular disease (CVD). These six patients comprised the 5.7% of young adults under < 45 years old with cerebrovascular accident admitted over the 6-year period. CONCLUSION: SLE and APS either primary or secondary to SLE were the most common underlying systemic autoimmune rheumatic diseases, in patients presenting with a neurological event of acute onset. Young adults (< 45 years old) with CVD should undertake screening for SLE/APS.

Normal bone marrow hematopoietic stem cell reserves and normal stromal cell function support the use of autologous stem cell transplantation in patients with multiple sclerosis.

Bone marrow (BM) stem cell reserves and function and stromal cell hematopoiesis supporting capacity were evaluated in 15 patients with multiple sclerosis (MS) and 61 normal controls using flow cytometry, clonogenic assays, long-term BM cultures (LTBMCs) and enzyme-linked immunosorbent assays. MS patients displayed normal CD34+ cell numbers but a low frequency of colony-forming cells (CFCs) in both BM mononuclear and purified CD34+ cell fractions, compared to controls. Patients had increased proportions of activated BM CD3+/HLA-DR+ and CD3+/CD38+ T cells that correlated inversely with CFC numbers. Patient BM CD3+ T cells inhibited colony formation by normal CD34+ cells and patient CFC numbers increased significantly following immunomagnetic removal of T cells from BMMCs, suggesting that activated T cells may be involved in the defective clonogenic potential of hematopoietic progenitors. Patient BM stromal cells displayed normal hematopoiesis supporting capacity indicated by the CFC number in the nonadherent cell fraction of LTBMCs recharged with normal CD34+ cells. Culture supernatants displayed normal stromal derived factor-1 and stem cell factor/kit ligand but increased flt-3 ligand levels. These findings provide support for the use of autologous stem cell transplantation in MS patients. The low clonogenic potential of BM hematopoietic progenitors probably reflects the presence of activated T cells rather than an intrinsic defect.