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.

Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing.

BACKGROUND: Horizontal gaze palsy and progressive scoliosis (HGPPS) is caused by mutations of the ROBO3 gene, which encodes a receptor associated with axonal guidance during development. Although there is evidence for uncrossed cuneatal and corticospinal tracts in HGPPS, it is unclear whether other central nervous system pathways are involved. OBJECTIVE: To study two patients with HGPPS homozygotic for the ROBO3 E319K mutation using a variety of neurophysiological and neuropsychological tests. METHODS: A battery of neuropsychological tests was applied to assess various cognitive and perceptual functions. The corticospinal, somatosensory and auditory pathways were evaluated using appropriate neurophysiological tests. To access motor pathways to the neck muscles, electromyographic recordings were obtained from the sternocleidomastoideus and splenius capitis muscle during active head rotation. RESULTS: Both patients performed normally on manual dexterity, complex sensory and visuospatial functions, reading and general intelligence tests. Motor evoked potentials in both patients showed uncrossed corticospinal tracts for the extremities, although in one patient, electromyography indicated pyramidal tract crossing for the neck muscles. Although somatosensory evoked potentials showed uncrossed somatosensory fibres subserving proprioception and light touch, right median nerve somatosensory evoked potential in one patient indicated a partial lemniscal crossing. Sympathetic skin response and blink reflex showed a midline crossing of the spinothalamic and quintothalamic tracts. Brain stem auditory evoked potentials indicated a lack of crossing in the level of the trapezoid body. CONCLUSIONS: Our patients with the ROBO3 E319Kappa mutation show normal perceptual and cognitive functions and have both crossed and uncrossed motor, sensory and auditory pathways.