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Introduction: Multiple sclerosis (MS) is a multifocal chronic inflammatory demyelinating disease of the central nervous system. Axonal damage correlates with the presence of macrophages and CD8+ T-lymphocytes at brain lesions. The gold standard of therapy at MS relapse are iv glucocorticoids (GC). The aim of the study was to assess the changes on the different subsets of circulating CD8+ T-lymphocytes at relapse and after iv GC therapy., Patients and Methods: We consecutively studied 20 patients at MS relapse before and at day 5 after initiation of i.v. methyl-prednisolone (MP) therapy (1 g/day for 3-5 days). CD4+ and CD8+ T-lymphocytes subsets were studied by multiparametric flow-cytometry. As control group, 18 healthy subjects were studied., Results: Treatment with i.v. MP suppressed activated (CD8+CD38+HLA-DR+, p=0.05) and effector memory (CD8+CD27-CD45RO+) T-lymphocytes (p=0.07). By contrast, an increase of naïve (CD8+CD27+CD45RO-) (p=0.07) and regulatory CD8+CD25+ T-lymphocytes was observed (p<0.002). At MS relapse, there was an inverse correlation between regulatory CD8+CD25+CD28- T-lymphocytes and activated CD4+ (r = -0.6; p=0.012) and CD8+ (r = -0.66; p=0.004) T-lymphocytes. After i.v. MP treatment, positive correlation between regulatory CD4+CD25+high T-lymphocytes and CD8+CD25+ T-lymphocytes was observed (r=0.74; p<0.0001)., Conclusions: Our data suggest that i.v. MP may contribute to changes observed on the differentiation of CD8+ T-lymphocytes, namely blocking their complete maturation, and expansion of regulatory CD8+ T-lymphocytes. We hypothesize an additional effect of i.v. MP in inhibiting axonal damage which may add a neuroprotective effect on MS relapse.

Objectives: To study the management of pregnancy in multiple sclerosis (MS) patients on immunomodulatory therapy (IMT) in routine clinical practice and to analyze pregnancy outcomes and the clinical course of MS around pregnancy., Methods: Retrospective, multicentric study in Spain in MS patients receiving IMT before conception and followed for at least three months post-partum., Results: A total of 1286 medical records were reviewed. Eighty-eight pregnancies were identified in 74 (6%) women, 66% of which were unexposed and 34% exposed pregnancies. In most cases, IMT was discontinued before conception and resumed shortly after delivery. Accidental exposure to IMT did not lead to higher rates of abortions (P = 0.76) or malformations. The relapse rate was decreased during pregnancy (0.31 versus 0.61 in the pre-pregnancy year) and increased after delivery (0.87 on month 3), returning to pre-conception values on month 12. The median EDSS score was not increased during the study., Conclusions: Discontinuation of IMT before conception, and resumption shortly after delivery was the most frequent clinical practice procedure. Accidental exposure to IMT did not affect pregnancy outcomes or increased malformation rates. Pregnancy was associated with a reduced relapse rate. No factor was found to predict the risk of relapses during or after pregnancy.

Objective: The Fatigue Impact Scale for Daily Use (D-FIS) is an eight-item instrument designed to measure subjective daily experience of fatigue. This study sought to determine the metric properties of the D-FIS in multiple sclerosis (MS) patients., Methods: Sixty-eight patients with operationally-defined MS and fatigue (54.8% of the sample) underwent the D-FIS. Usual clinical measures for MS, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Functional Assessment of Multiple Sclerosis (FAMS) were also applied. In addition, patients with fatigue completed the Fatigue Descriptive Scale, the Multidimensional Fatigue Inventory (MFI), a Visual Analogue Scale for Fatigue (VAS-F), and a Global Perception of Fatigue Scale (GPF)., Results: Full computable data, 95.6%; both floor and ceiling effect=1.54%; item-total correlation=0.62 (item 1) to 0.84 (item 6); Cronbach's alpha=0.91; item homogeneity =0.55; standard error of measurement=3.18; convergent validity with other fatigue measures=-0.57 (VAS-F); 0.52 (GPF); and 0.46 (MFI-general fatigue). Test-retest reliability (ICC)=0.81. There was a strong association between health-related quality of life (HRQoL) (FAMS) and D-FIS (rS=0.70)., Conclusions: In this study, D-FIS proved to be a feasible and valid instrument for measuring MSrelated fatigue, a frequent symptom associated with deterioration of patients' HRQoL.

Interferon beta-1a (IFNâ-1a) has demonstrated efficacy in multiple sclerosis (MS), although its mechanism of action remains only partly understood. We evaluated the ex vivo and in vitro effects of IFNâ-1a (Rebif) on regulatory T-cell (T(Reg)) function in 22 relapsing-remitting MS patients and 16 healthy controls. T(Reg) function was significantly enhanced after 3 and 6 months of IFNbeta-1a therapy. Furthermore, there was a trend towards increasing proportions of total CD4(+)CD25(+) and CD4(+)CD25(+)GITR(+) T(Reg) after 6 months of IFNbeta-1a therapy when compared with baseline. In conclusion, IFNbeta-1a therapy enhances T(Reg) function, and this may be relevant in the inflammatory environment of MS lesions.

Glucocorticoids remain the treatment of choice for MS relapses. However, little is known on the effect of intravenous methylprednisolone (IVMP) on dendritic cells (DCs) and regulatory T-cells (TReg). Our main goal was to quantify circulating myeloid and plasmacytoid DCs (mDCs and pDCs), and TReg at MS relapse versus healthy controls; and to analyse the short-term changes after IVMP for MS relapse. MS patients at relapse compared to controls showed higher %CD4+CD25high+ TReg (p<0.01). After 5-days of IVMP, activated T-lymphocytes (p=0.001), pDCs (p<0.0001), and CD11c+ mDCs (p<0.0001) decreased. By contrast, CD4+CD25+ and CD4+CD25high+ TReg further increased (p<0.0001 both). Changes on these subsets may play a relevant role in the immunosuppressive activity of this drug.

Pregnancy represents a physiological transitory state of immune tolerance to avoid the rejection of the foetus, and concomitantly of stabilisation of many autoimmune diseases, such as multiple sclerosis (MS). Alterations in regulatory T-lymphocytes (T(Reg)) are known to be involved in organ-specific autoimmune disease pathophysiology. Our goal was to quantify CD4+ CD25+ and CD4+ CD25hi+ T(Reg) and activated (CD4+ HLA-DR+ CD38+) T-lymphocytes during pregnancy and puerperium in 13 MS patients in comparison with healthy pregnant and non-pregnant women. During pregnancy, a progressive parallel increase in CD4+ CD25+ T-lymphocytes in healthy pregnants as well as MS pregnant patients was observed. The proportion of T(Reg) was significantly higher in all pregnants than in non-pregnant women (p=0.01), whereas no differences were observed neither in the percentages of total nor activated CD4+ T-lymphocytes. In MS patients, CD4+ CD25+ T-lymphocytes significantly decreased when comparing the third trimester with the puerperal period proportions (p = 0.01), whereas CD4+ CD25hi+ T-lymphocytes significantly increased (p = 0.002). Our findings are consistent with the expansion of circulating regulatory CD4+ CD25+ T-lymphocytes pool with suppressive activity during normal pregnancy and in MS. A different pattern of CD+ CD25hi+ T-lymphocytes between healthy pregnants and MS women, which may represent relevant factors in the activity course of MS.

Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disorder associated with hypergammaglobulinemia and circulating autoantibodies. Two patients previously diagnosed with multiple sclerosis who developed AIH are reported. One patient showed acute presentation with fulminant hepatic failure requiring liver transplantation. Serum autoantibodies were negative in both patients but a characteristic clinical course in the first patient as well as the hepatic histological features with typical pathological changes of AIH in both patients and a score compatible with AIH established the diagnosis.

Multiple sclerosis (MS) is an immune-mediated disease with a clear sex-bias that may be attributed to sex hormones, sex' linked genes or both. Here we sought to determine the evolution pattern of cortisol and sex hormones at MS relapse and 2-months later in 7 male patients with relapsing remitting MS, and whether there was a correlation with a specific Th1 and Th2 cytokine pattern. Our findings indicate the activation of the hypothalamic-pituitary-adrenal axis and the concomitant upregulation of pro- and anti-inflammatory cytokines during relapse. The further increase of sex hormones, in particular estradiol in our male MS patients suggest their possible implication in the physiopathology of the illness and a putative anti-inflammatory and neuroreparatory effect.

Aims: To review the clinical concept of an attack, the physiopathological mechanisms underlying the symptoms of the attack, in the recovery phase, and those corresponding to the progressive or degenerative phase of the disease., Development: Although they do not explain the exact mechanisms responsible for the onset of the attack or the processes that account for the clinical and pathological heterogeneity, most research studies suggest that the lesions produced in multiple sclerosis are the consequence of complex immunological interactions that take place mostly in the white matter of the central nervous system. These lesions affect, to variable extents, the myelin and the axon. We survey how these events are reflected in the images obtained by magnetic resonance. Clinical observations have shown that, in some patients, infections and hormones can exert an influence on the activity of the disease. Recovery, in the initial stages at least, would be produced by the action of poorly understood mechanisms that limit inflammation, and by local or cortical neuroplasticity or repair processes. Finally, we discuss the mechanisms behind the action of corticoids that justify their use when treating these attacks., Conclusion: A more thorough understanding of these events opens up the way to providing better therapy in the future.

Introduction: Multiple sclerosis is a chronic neurological disorder which affects middle aged adults. It usually means serious physical, psychological, social and employment problems for the patients concerned., Method: From the anatomo pathological point of view, it is characterized by demyelination and axon damage in the central nervous system. The clinical features are variable, depending on the course of the disease, its clinical form and the sites of the lesions. Symptoms may appear in bouts, as relapses of the disorder or as a result of incomplete recovery from these episodes and cause severe disability., Conclusion: We review the physiopathology and most widely used treatment for management of the commonest symptoms of multiple sclerosis.

Objective: The cross-sectional study evaluated the psychometric properties of the Functional Assessment of Multiple Sclerosis (FAMS) Spanish version and its use in measuring quality of life (QOL) of multiple sclerosis (MS) patients in Spain., Methods: The FAMS is a factorially derived self-report scale designed to assess six primary aspects of QOL of patients with MS: Mobility, Symptoms, Emotional Well-Being, General Contentment, Thinking and Fatigue, and Family/Social Well-Being. Its Spanish translated version was used to assess QOL of 625 MS patients recruited in an outpatient clinic setting from 58 hospitals in Spain. Internal consistency of the Spanish FAMS was evaluated Multiple regression analyses were performed to identify significant predictors from demographic, clinical and treatment characteristics, and Kurtzke Expanded Disability Status Scale (EDSS) scores in predicting FAMS scale scores., Results: Most of the patients are females (66%), and 74% were of the relapsing-remitting (RR) clinical subtype. Cronbach's alpha coefficients were high (range=0.78-0.96), indicating subscale homogeneity comparable to that of the original English version. Linear multivariate regression analyses revealed that the EDSS is a dominant variable in predicting all the FAMS subscales, especially mobility (R2=0.51) and the total scores., Conclusions: The Spanish FAMS is a psychometrically valid instrument that allows clinicians and clinical researchers the ability to measure the QOL concerns of MS patients in Spain.

Tumor necrosis factor (TNF-alpha) and IL-10 are key regulators of the T helper (Th)1/Th2 balance, which is critically skewed in many pathological conditions including immune-mediated inflammatory diseases of central nervous system (CNS) such as multiple sclerosis (MS). Nitric oxide (NO) has been reported to have dual effects on CNS pathology, and to play an important role in MS. We performed a cross-sectional study in 17 randomly selected patients during MS flare-up, and compared levels of TNF-alpha, IL-10 and NO in serum and cerebrospinal fluid (CSF) with the serum values of these mediators in two different control groups, healthy subjects and HIV-infected untreated patients. Serum and CSF values of TNF-alpha, IL-10 and NO were higher in MS patients than in the serum of healthy controls. Two MS patients showed increased levels of NO in CSF, with inversion of the NO(SERUM)/NO(CSF) quotient, which is clearly indicative of an intrathecal production of NO. No correlation among the values of both cytokines and NO, and the laboratory parameters analysed in MS patients (IgG index, presence of IgG oligoclonal bands and albumin quotient) was found. The high levels of TNF-alpha and IL-10 (both in serum and CSF) accompanying an MS attack suggest a simultaneous expression of Th1 and Th2 cytokines as opposed to sequential expression of Th1 followed by Th2 as described in the models of experimental autoimmune encephalomyelitis (EAE). Globally, our results support the inherent heterogeneity of the disease.

Introduction: Occasionally intracranial tumors present a clinical picture similar to that seen with transient ischemic attacks (TIA). The mechanism for this is not clear. The differential diagnosis of these two disorders is important since their treatment is quite different., Clinical Cases: Two men and two women aged between 53 and 72 years of age, with no known cardiovascular risk factors, complained of one or several episodes of neurological deficit (hemisensitive deficits, transient blindness and isolated aphasia), lasting between 3 minutes and 6 hours. Neuroimaging investigations (CT and MR) showed images compatible with space occupying lesions localized to the convexity (parietal, frontotemporal and frontoparietal) and in one case at the edge of the sphenoid bone. Three patients were operated on. The lesions were confirmed as tumors (two cases of meningiomas and one of glioblastoma). Symptoms did not recur after a mean follow up period of nine months. Various mechanisms have been suggested to explain this phenomenon: vascular compression due to pressure from the mass, changes in intracranial pressure, vascular steal phenomenon, negative focal seizures, Leao s cortical depression and others. The absence of risk factors which would justify a vascular cause, the correlation between localization of the tumour and the clinical signs, and the disappearance of symptoms following surgery would seem to support the hypothesis that in our cases the symptoms observed were due to intracranial space occupying lesions., Conclusion: The presence of an intracranial tumour should be ruled out by using neuroradiological investigations in patients complaining of transient episodes of neurological deficits.

Objective: To determine the frequency and significance of antinuclear (ANA), anticardiolipin (ACA) and anti-Ro (SS-A) antibodies in multiple sclerosis (MS) patients., Methods: ANA (indirect immunofluorescence), ACA and anti-Ro (SS-A) antibodies (ELISA) were tested in sera of 42 patients with Poser defined MS and 50 healthy individuals., Results: High levels of anti-Ro (SS-A) antibodies were found in 3 patients (7%) (vs 0 in the control group). Two of them had normal salivary gland biopsy. Clinical MS form was chronic-progressive in 2 cases and relapsing-remitting in the third one. Ten patients (23%) had low levels of ANA (vs 4%), none of them positive for anti-Ro (SS-A) antibodies. Only 1 patient (2%) with RR clinical form had ACA (vs 0). No clinical or neuroradiological differences with conventional MS patients were observed., Conclusions: ANA, ACA and anti-Ro (SS-A) antibodies in MS patients indicate an underlying autoimmune disease but our series suggests that they are an epiphenomenon of a more diffuse immunological dysfunction.

Introduction and Objectives: Multiple sclerosis (MS), as a chronic, incurable and often severely disabling disease, greatly affects patients normal life. The objectives of the study are to analyze which aspects of daily life are more affected by the disability and to investigate whether the degree of support demanded by patients is related to their level of incapacity., Patients and Methods: Group of 60 ambulatory patients with Poser defined MS, mean age of 44.5 years, Expanded Disability Status Scale (EDSS) of 3.1, and average period of disease evolution 13.2 years. Test instrument was a structured 12 items questionnaire given during a visit to the attending physician and regarding social and family aspects, financial needs, professional life and emotional well being., Results: 58.3% of the professionally active patients had to give up their jobs; 8.3% experienced changes in their marital status and general family life somewhat changed in 41.7% of the cases due to either physical or psychical disease consequences. Social relationships were altered in 68.2% of the cases; 43.3% required some level of economical support, and 80% went through episodes of emotional distress., Conclusion: Statistically significant relationships exist between level of incapacity and professional and social life changes but not with family life changes, emotional alterations and level of support required.

Introduction: The treatment of prolonged, severe relapses in multiple sclerosis (MS) patients who respond poorly to high-dose intravenous corticosteroids is not yet established. Plasma immunoadsortion (IA) removes immunoglobulins (IgG), immune complexes, and complement from plasma. It may bear some advantages compared to plasmapheresis, a nonselective procedure that requires substitution of patient plasma by colloids solutions or plasma, which may carry a potential risk for viral infections., Patients and Methods: Three relapsing-remitting MS patients with a malignant course received IA. All they were experiencing a prolonged relapse unresponsive to high-dose intravenous corticosteroids, causing a locked-in state in two of the patients and severe pseudobulbar impairment in the third one. Five to six IA consecutive sessions were administered along a 7-10 days course., Results: IA was followed by a prompt and unequivocal clinical response in all three patients, which paralleled a decrease in IgG, fibrinogen, and C3 complement serum levels. IA administration was followed by immunosuppressor therapy, either with cyclophosphamide and intravenous ACTH (2 cases) or mitoxantrone (1 case). Improvement has been sustained along a mean follow-up of 7.6 years (range: 7-8.5 years), only one of the patients suffering two mild clinical relapses., Conclusion: We believe that IA may be useful, either as a coadyuvant or alternative treatment in severe relapses in MS patients that do not respond to high-dose intravenous corticosteroid therapy.

To elucidate whether serum coenzyme Q10 levels are related with the risk for multiple sclerosis (MS) or are a marker for the activity of the disease, we compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio, in 31 patients with MS (during exacerbations) and 19 matched controls using a high performance liquid chromatography technique. The mean serum coenzyme Q10 levels and the coenzyme Q10/cholesterol ratio did not differ significantly between the 2 study groups. The values did not correlate with age, age at onset, and duration of the disease. These results suggest that serum coenzyme Q10 concentrations are unrelated with the risk for MS and are not a useful marker of activity of the disease.

It has been suggested that nitric oxide (NO) could be implicated in the pathogenesis of multiple sclerosis (MS). Recently, two groups reported increased cerebrospinal fluid (CSF) nitrate levels (oxidation product that provides an indirect estimation of NO) in MS patients. However, another group did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic cadmium reduction method in 11 MS patients and 25 matched controls. The CSF nitrate levels and the CSF/plasma nitrate ratio did not differ significantly between the two study groups. Plasma nitrate levels were nearly significantly lower in MS patients. CSF and plasma nitrate levels did not correlate with age at onset and duration of the disease in the patient group. These data suggest that measurement of CSF levels of nitrate is not a marker of the activity of MS.

Introduction: Recognition of different ictal motor patterns in psychogenic seizures may be useful in terms of differentiation from epileptic seizures and may also improve understanding the underlying psychopathology., Objective: To outline recognizable ictal motor patterns that may help to distinguish psychogenic motor seizures from epileptic convulsive episodes., Patients and Methods: Chart review from 54 patients with motor psychogenic seizures and no clinical or EEG evidence of concomitant epilepsy., Results: Only 5 patients (9.2%) experienced more than one ictal motor pattern along their illness. Categorization into four subtypes according to ictal motor behaviour was possible in all other patients: psychogenic seizures with flaccid unconsciousness (32.6%), combativeness (32.6%), a hypermobile subtype (24.4%) as defined by the presence of intentional movements or slow rhythmic oscillations of a segment or the entire body, and rigidity (10.2%)., Conclusions: Many psychogenic motor seizures consistently present with recognizable motor phenomena which may be readily identified providing the availability of a reliable witness. Psychogenic seizures as presented spontaneously in a general neurology setting may differ from those reported in biased referrals to video-EEG laboratories. Recognition of characteristic patterns may help differentiation from tonic-clonic convulsions, avoid unnecessary examinations, and may provide insights into their underlying psychopathological mechanisms.

We compared cerebrospinal fluid (CSF) and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 36 patients with multiple sclerosis (MS) and 32 matched controls. The mean CSF vitamin E levels and the CSF/serum vitamin E ratio did not differ significantly between the two study groups. The serum levels of vitamin E and the serum vitamin E/cholesterol ratio were significantly lower in MS patients when compared with controls (P < 0.05 and P < 0.01, respectively). These values were not correlated with age, age at onset and duration of the disease in the patients group. These results suggest that CSF vitamin E concentrations are not a marker of activity of MS activity.

Introduction and Clinical Case: We present a case of extra-pontine myelinolysis caused by acute hypernatraemia in which a complex picture of late onset extrapyramdial features, choreodystonia and parkinsonism developed. Repeated physical examinations, neurophysiological and neuroimaging studies using magnetic resonance all indicated an extra-pontine site of the lesions, which symmetrically affected the striate and to a lesser extent both thalami. We review the relevant literature available and analyze the cases described as having abnormal movements associated with a myelinolytic syndrome., Conclusions: Extra-pontine myelinolysis is a cause of acquired dystonia, chorea and parkinsonism, generally of late onset and with varying response to treatment. The association of hypernatraemia, hyperglycaemia and liver transplant seem to predispose to the development of extra-pontine lesions.

Introduction: It may be difficult to determine the adequate mement, the information content and the most convenient person to inform patients with chronic, incurable disorders with uncertain prognosis as sclerosis multiple (MS)., Material and Methods: To gain information on how these aspects had been carried-out and the extent to which patients felt satisfied, we studied 60 definite MS ambulatory patients by means of a semistructured questionnaire attending a hospital-based MS unit. The results were compared with those from 40 patients with rheumatoid arthritis (RA), a chronic disabling disorder of the locomotor system with variable course, examined in a similar way., Results: In the vast majority of patients (81.7 and 82.9%, respectively) in both groups the diagnosis had been delivered by a specialist, a point on which most patients agreed upon as convenient. However, most MS patients (78.4%) and nearly all of those with RA (97.6%) should have desired to receive information on their diagnosis as soon as this might had been firmly established. Though more than half the patients (61.7 of MS and 56.1% of RA) admitted to have developed depressive symptoms following information on their diagnosis, a majority expressed their desire to have been informed early about 'all the truth' regarding their prognosis (78.4 and 87.8%, respectively)., Conclusions: Though data from this study should be taken with caution when applied to MS patients shortly after experiencing their first symptoms, and it is therefore unwise to give rigid rules, the vast majority of MS patients express the desire to receive early, accurate, and individualized information on their diagnosis provided by a competent specialist.

Introduction and Development: Multiple sclerosis (ME) is an inflammatory disease of the myelin of the central nervous system, the origin of which is still unknown. Genetic, infectious, immunological and environmental factors have all been blamed, but none of these factors on their own can explain the whole spectrum of this disease. Of the environmental factors, fat in the diet has given rise to most discussion. At the present time, it is known that polyunsaturated essential fatty acids form a part of biological membranes. A relationship has been found between the dietary fat consumed and the plasma levels and cell membrane content., Conclusions: The possible immuno-modulation function of these fatty acids justify rigorous evaluation of this hypothesis.

The course and prognosis of adult patients who recover from acute and extensive inflammatory demyelination, variously termed fulminant or Marburg's type of multiple sclerosis (MS), is poorly known. We report long-term magnetic resonance imaging (MRI) and neuropsychological findings in two patients who developed acute psychosis and a state resembling akinetic mutism, with CT scan evidence of extensive cerebral white matter damage. Both patients ultimately recovered, but were left with a severe, non-progressive dementia with prominent frontal lobe signs unassociated with motor impairment. Extensive residual MRI lesions with evidence of tissue destruction in the white matter and callosal atrophy were visible many years after the initial event One of the patients developed a single relapsing-remitting episode with multifocal neurological deficits several years after the onset, whereas the condition remained monophasic in the other patient during an 8 year follow-up. Our observations suggest that while patients with so-called "fulminant" demyelinating disorders may nowadays survive with supportive measures, the disorder may remain stabilized for many years following disease onset., (1997 Lippincott Williams & Wilkins.)

Recent reports have shown association between CYP2D6 polymorphism and neuronal degenerative diseases such as Parkinson's disease. We investigated the association between this polymorphism and the risk for developing multiple sclerosis (MS). Leucocyte DNA from 118 MS patients and a control group of 200 unrelated healthy individuals was studied for the occurrence of 8 different CYP2D6 allelic variants by using allele-specific PCR amplification, XbaI and EcoRI RFLP analyses. The frequencies for these allelic variants in the MS and control groups were, respectively: CYP2D6wt 75.0% and 79.3%, CYP2D6A 0.4% and 1.3%, CYP2D6B 11.4% and 12.0%, CYP2D6C 4.2% and 2.0%, CYP2D6D 3.0% and 2.3%, CYP2D6L 0.8% and 0.3%, CYP2D6L2 5.1% and 3.0%. The frequencies of subjects with high CYP2D6 activity (those carrying two or more functional genes) were 77.1% and 73.5% in MS and control groups. The frequencies of subjects with absent CYP2D6 activity (those lacking functional genes) were 3.4% and 4.5% in MS and control groups, respectively. These results indicate that mutations at the CYP2D6 gene do not seem to be a factor in determining susceptibility to MS.

To elucidate whether any relationship exists between genetic polymorphic acetylation and the risk for multiple sclerosis (MS), we determined this polymorphism, using sulphamethazine, in 71 patients with definite MS and in 268 age-matched controls. Thirty-seven patients (52.1%) and 151 controls (56.3%) were classified as slow acetylators (not significant difference). No relation was found between acetylator polymorphism and age at onset of disease in MS patient's group. Our results do not support the existence of any relationship between acetylator polymorphism and the risk for MS.

A fermentation process for the microbial production of a new lipid surface-active compound, 7,10-dihydroxy-8 (E)-octadecenoic acid (OCD), has been established using a vegetable oil as carbon source in a coordinated carbon/nitrogen feed strategy. The surfactant was produced during the logarithmic growth phase. Aeration was the most critical parameter for product formation. Up to 7 g product/l was produced.

Two brothers developed a slowly progressive paraparesis during adulthood, lately associated in one to primary adrenal and gonadal insufficiency but no electrophysiological evidence of peripheral nerve involvement. Both patients and an asymptomatic sister had increased plasma concentrations of very-long chain fatty acids (VLCFA). A CT-scan of the propositus was initially normal but showed at follow-up diffuse white matter hypodensities consistent with severe demyelination of the centrum semiovale. The appearance of the lesions remained unchanged for the next two years without clinical evidence of supraspinal changes in despite of progression of the paraparesis. We believe that these observations further support a link between the severe infantile variety of adrenoleukodystrophy and the more protracted adult-onset variants. Further, CT-scan in families with spastic paraparesis may be of help in detecting early evidence of an underlying diffuse white matter disorder, eventually supported by more conclusive studies as VLCFA determinations.

Neurocysticercosis (NCC) in Spain remains localized in well-defined endemic areas. Due to massive immigration from these rural areas toward urban outskirts under expanding industrialization during the 1960s and the widespread used of CT-scan, a relatively large number of NCC cases were subsequently detected in some hospitals in Madrid, reportedly with a trend towards decline from 1970 onwards. We carried-out an estimation on the frequency of this disease covering a 10-year period (1980-1989) by tracing all suspected diagnosis of NCC by CT-scan in Madrid General Hospital, one of the largest centers in this city covering some 672,351 people. Thirteen cases fulfilling diagnostic criteria for NCC has been seen by different clinical services for the past 10 years, mostly by neurologists. The patients were evenly distributed along the study period. Eleven patients were Spaniards, and all but two were born in geographic areas recognized as endemic for the disorder, mainly Castilla, Extremadura and Andalucia. At least 38 per cent of the patients were detected by CT-scans performed for unrelated conditions. Only 5 patients were considered to be suffering from active CNS infestation on the basis of CSF pleocytosis, immune CSF reactions for NCC or both. Most cases were adults or aged individuals (mean age, 46 years) but the only two Spanish adolescents were born in Madrid city. Two patients were of Hispanic origin (Chili and Venezuela), comprising some 25 per cent of all NCC seen for the past five years.

A clinical and electromyographic study of oculomotor function was carried out in a series of 24 patients with amyotrophic lateral sclerosis (ALS). In 15 cases an alteration of Bell's phenomenon was found. In addition, three patients showed some impairment of conjugate ocular motility in the form of upward gaze paly. All cases had preserved oculocephalic reflexes in the vertical and horizontal planes. On clinical and electromyographic grounds, three degrees of altered Bell's phenomenon are suggested: attenuated (short and unsustained upward displacement of the eyeballs after forced closure of the eyelids), abolished (no upward displacement), and inverted (downward instead of upward displacement of the eyes). These oculomotor alterations were not directly related to the type of ALS at onset of the illness, nor with its duration. However they were correlated with the relative degree of the clinical bilateral pyramidal tract signs at the supraspinal level. The common involvement of the corticogeniculate tract in ALS could explain the unexpectedly high incidence of alteration of Bell's phenomenon found in this disease, but is is non-specific and similar lesions from different causes may also produce it.