Antiphospholipid antibodies (aPL) have been suggested to play a role in causing cognitive and behavioral impairments. In the present study we investigated the pathogenic potential of aPL by intracerebro-ventricular (ICV) administration of immunoglobulins (IgG) from patients with antiphospholipid syndrome (APS). IgG, purified from the sera of four APS patients, was tested for binding to normal mouse brain by immunohistological staining. These IgG (7.5 microg) were injected ICV unilaterally to male C3H mice. Mice injected with IgG purified from pooled sera derived from healthy subjects served as controls. The mice were examined neurologically for motor function and coordination, and cognitively in a Morris water maze. The cognitive tests were performed with the experimenter blinded to the treatment. The performance of the mice in four separate experiments was compared by analysis of variance with repeated measures. IgG from one APS patient was found to bind best to neuronal structures in the hippocampus and cerebral cortex. Mice (n = 43) injected with this IgG performed worse in the water maze compared to the controls (n = 45) with significant effects of the aPL IgG on the overall performance of the mice (treatment, P < 0.03), on learning throughout the experiment (treatment x day, P < 0.02) and on short term memory (treatment x day xtrial, P < 0.002). IgG injected from two of the three other patients also bound specifically to mouse brain neurons and produced an impairment in performance of the water maze. These results support the hypothesis that aPL that gain access to the central nervous system may play a direct role in the pathogenesis of neurological manifestations of APS.

The effects of the cerebellum on cognitive functions (CF) are poorly known and inadequately studied. Neurological, neuropsychological, and neuroimaging studies were performed on 25 non-random patients (14 female, 11 male, mean age 51.8 +/- 18.0 years) with isolated cerebellar infarcts. Cognitive impairments (CI) were seen in 22 patients (88%). These included impairments of attention, planning, control, abstract thought, memory, and speech disturbances (naming difficulties, irregularity of speech, agrammatism, dysprosodia), visuospatial and quasispatial disturbances, and counting impairments, demonstrating dysfunction of the anterior and posterior associative areas of the cortex. The extent of CI varied: 16 patients (64%) showed impairments only in neuropsychological tests, while six (24%) had clinically apparent impairments. Clinically significant CI developed in lesions of particular areas (posteroinferolateral and posteromedial/median) of the cerebellar cortex associated with the dominant hemisphere of the brain. The existence of clinically significant CI was independent of infarct size: infarcts were smaller (mean 5.65 cm3) in patients with marked impairments than in others (mean 12.8 cm3). The typical signs of cerebellar infarcts (ataxia, vertigo, vomiting) were seen in all patients with clinically insignificant and in only two of six patients with clinically significant CI. The present studies demonstrated the involvement of the cerebellum in the modulation of CF. The extent of CI in cerebellar infarcts depended on infarct location. The topical localizations of cerebellar zones controlling CF and movement are different.

We studied 24 patients (18 women, 6 men), aged 29 to 54, with Sneddon's syndrome. The clinical picture of Sneddon's syndrome was characterized by cerebrovascular disorders, livedo reticularis, disturbance of peripheral circulation, arterial hypertension, cardiac pathology (ischemic heart disease, heart murmurs), complicated obstetric history in women, and disturbed sexual function in men. In 6 of 17 examined patients with Sneddon's syndrome there was a high concentration of anticardiolipin antibodies (ACA) but no antibodies to native DNA and LE cells. The course of the disease in the patients with a high ACA level, when compared with normal ACA level patients, was characterized by a more rapid progression and more severe clinical manifestations. The study demonstrates the similarity of clinical symptoms and immunologic disturbances in Sneddon's syndrome and the antiphospholipid syndrome and suggests the importance of ACA in the pathogenesis of some cases of Sneddon's syndrome.

Forty-six patients (33 women, 13 men, mean age 40 years) with Sneddon''s syndrome characterized by an ischemic cerebrovascular disease combined with widespread livedo were studied. The clinical picture also included fetal loss (20 of 29 women who had become pregnant), peripheral venous thrombosis (12 patients), ischemic heart disease (18 patients), thrombocytopenia (8 of 40 patients), arterial hypertension (27 patients), headache (38 patients), and epileptic seizures (5 patients), and was similar to that of the antiphospholipid syndrome (APS). In 36 of 46 (78%) patients antiphospholipid antibodies (aPL) were found: anticardiolipin antibodies >5 GPL in 23 of 46 (50%) and lupus anticoagulant in 26 of 43 (61 %) patients. The presence of clinical and immunological manifestations of the APS in 78% of patients in the absence of typical systemic lupus erythematosus features allows one to consider these Sneddon''s syndrome cases as examples of primary APS. The pathogenesis of Sneddon''s syndrome in aPL-negative patients needs to be clarified.

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Antiprothrombin antibodies (aPT), a new serologic marker of antiphospholipid syndrome, were studied in 46 patients randomly selected from 73 with Sneddon's syndrome and 20 matched normal controls. aPT were elevated in 26 patients (57%) and were not found in any of the controls. The addition of aPT data increased the proportion of Sneddon's syndrome patients with at least one type of antiphospholipid syndrome marker from 65 to 78%. The finding that aPT are common in Sneddon's syndrome supports the hypothesis that Sneddon's syndrome is a form of antiphospholipid syndrome.

Autoantibodies (Ab's) to the "B" peptide (amino acids 372-395) of glutamate/AMPA receptor subtype 3 (GluR3) are found in serum and cerebrospinal fluid of some patients with different types of epilepsy. Since such anti-GluR3B Ab's can activate and/or kill neurons in vitro and in vivo, they may contribute to epilepsy. To investigate whether anti-GluR3B Ab's may also be relevant to epilepsy when it accompanies some autoimmune-diseases, we tested for these Ab's in patients suffering from epilepsy that accompanies anti-phospholipid syndrome (APS) or Sneddon's syndrome (SNS), both being autoimmune-diseases with frequent neurological complications. We tested 77 pediatric patients whose epilepsy is their main disease; 31 adult patients whose epilepsy accompanies APS (primary or SLE-associated) or SNS; 45 epilepsy-free APS and SNS patients; and 90 healthy controls. Compared to the controls, significantly elevated anti-GluR3B Ab's were found in 22/77 (29%) patients whose epilepsy is their main disease, but in none of the patients whose seizures accompany APS or SNS. Yet, all the APS and SNS patients harbored the characteristic anti-phospholipid Ab's (aPL), directed against cardiolipin and beta2-glycoprotein I, and had lupus anti-coagulant. Thus, anti-GluR3B Ab's are not crossreactive with aPL, and not produced as a non-specific consequence of seizures on the one hand, or autoimmune-diseases on the other. Taken together with new findings accumulated recently in our lab, we suggest that anti-GluR3B Ab's are produced primarily in the periphery due to specific/non-specific "irritation" of the immune system, and that once they reach the brain via a leaky blood-brain barrier they may cause neuronal/glial damage and facilitate the outburst of epilepsy and additional neurological abnormalities. In contrast, the presence of anti-GluR3B Ab's does not seem to increase the probability of developing APS, SNS or the seizures that often accompany these autoimmune-diseases. These findings may have important diagnostic and therapeutic implications.

В последние годы в мире неуклонно растет интерес к диссекции артерий, кровоснабжающих головной мозг, -относительно новой и недостаточно изученной проблеме цереброваскулярных заболеваний. Ее основное клиниче-ское проявление -ишемический инсульт (ИИ), чаще раз-вивающийся в молодом возрасте. Изучение и прижизнен-ная диагностика диссекции церебральных артерий стала возможной благодаря широкому внедрению в клинику маг-нитно-резонансной томографии (МРТ). МРТ позволяет безопасно для больного проводить повторное ангиографи-ческое исследование, что важно для диагностики диссек-ции, поскольку она представляет собой динамическую па-тологию, а также с помощью режима Т1 с подавлением сиг-нала от жировой ткани (Т1 f-s) визуализировать непосредст- Dissection of internal carotid and vertebral arteries: clinical presentation, diagnosis, and treatment L.A. Kalashnikova Neurology Research Center, Russian Academy of Medical Sciences, Moscow The paper gives the data available in the literature and the author's results of an examination of almost 140 patients with dissection of the internal carotid and vertebral arteries (ICA and VA). Dissection is blood penetration through an intimal tear from the lumen of an artery into its wall to develop intramural hematoma (IMH). The cause of dissection is the weakness of the arterial wall