Showing papers in "Acta Neurologica Scandinavica in 1998"

Oxidative injury in the nervous system

Abstract: A free radical is a highly reactive chemical species that can react with organic macromolecules leading to cell and tissue damage and consequent functional disruption. Free radical or oxidative injury is increasingly recognized as an important factor in the pathophysiology of many human diseases, including those that affect the nervous system. This review summarizes important evidence implicating oxidative injury in the pathogenesis and progression of many important neurological disorders, including cerebrovascular disease, epilepsy, amyotrophic lateral sclerosis, and Huntington's disease. Results of controlled clinical trials of various antioxidant therapies in neurological disease performed to date are also highlighted.

Quality of life after a first ischemic stroke. Long-term developments and correlations with changes in neurological deficit, mood and cognitive impairment.

Abstract: Background - Studies on determinants of quality of life (QOL) after a stroke focus on one aspect (most important: neurological deficit, mood disorders or cognitivc failure) and as such provide no insight in the relative contribution of each factor on QOL. The groups of patients studied often contain victims of different types of stroke. This inhomogenity in patients leads to further confusion about QOL aftcr stroke. Objective - To evaluate in one study factors important for QOL in the period 3-12 months after a first one-sided ischemic stroke in the region of the middle cerebral artery. Design - Measurcs for QOL (Sickness Impact Profile, SIP), cognitive status (Wechsler Adult Intelligence Scale revised), mood and neurological deficit were scored 3, 6 and 12 months after the stroke. Setting - Successive patients admitted to a general hospital and rehabilitation clinic in The Hague, The Netherlands. Patients - A complete examination was performed three times in 35 patients. The results were compared to those of 20 controls matched for age, last occupation and educational level. Results - There was no significant neurological improvement between 3 and 12 months after the stroke. Cognition was impaired when compared to the estimated premorbid level and to the controls. There was incomplete recovery over the study interval. The patients as a group were depressed and remained so over the period of the study. The resulting quality of life scores were abnormal at 3 months and improved only slightly. Stepwise regression analysis revealed that depression and degree of paresis were the most important variables for the SIP total outcome. Conclusions - In a homogenous group of stroke patients the QOL improved somewhat in the period 3 to 12 months after the stroke but was still highly abnormal after 1 year. The decrease in QOL was correlated with depression and - to some degrec - with neurological deficit, but not to cognitive disturbances.

Sexual dysfunction in stroke patients

Abstract: Objectives – A marked decline in sexual activity has been reported in stroke patients. Little information, however, is available on clinical correlates of sexual dysfunction, changes in the sexual life of spouses of stroke patients, and abnormalities of nocturnal penile erections. Material and methods – In this prospective 6-month follow-up study, we assessed the impact of stroke on libido, sexual arousal, coital frequency and satisfaction with sexual life in 50 stroke patients (38 men, 12 women, aged 32 to 65 years) and in their spouses. We also measured nocturnal penile erections of the male patients using a strain gauge attached around the penis. Results – All the analyzed aspects of sexuality, i.e., libido, coital frequency, erection, ejaculation, vaginal lubrication, orgasm and satisfaction with sexual life, were commonly decreased as a consequence of stroke both in the patients and in their spouses. Fourteen (28%) patients at 2 months post-stroke and 6 (14%) patients at 6 months had ceased having sexual intercourse. Nocturnal erections at 2 months post-stroke were normal in 17 (45%) of the 38 male patients and impaired in 21 (55%) patients, but all of the patients had some nocturnal erections. Sexual dysfunction correlated significantly (P <0.05) with the presence of the sensory hemisyndrome. Conclusions – Sexual dysfunction and dissatisfaction with sexual life seems to be common both in male and female stroke patients and in their spouses. Decreased libido, sexual arousal and satisfaction are related particularly to the presence of the hemisensory syndrome. The etiology for sexual dysfunction after stroke is multifactorial including both organic and psychosocial factors.

Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson's disease with autonomic failure

Abstract: Objective - To selectively investigate postganglionic sympathetic cardiac neurons in patients with Parkinson's disease and autonomic failure. Material and methods - Metaiodobenzylguanidine (MIBG) is a pharmacologically inactive analogue of noradrenaline, which is similarly metabolized in noradrenergic neurons. Therefore the uptake of radiolabelled MIBG represents not only the localization of postganglionic sympathetic neurons but also their functional integrity. Ten patients with Parkinson's disease and autonomic failure underwent standardized autonomic testing, assessment of catecholamine plasma levels and scintigraphy with [ 123 I]MIBG. Results - The cardiac uptake of MIBG, as demonstrated by the heart/mediastinum ratio, was significantly lower in patients in comparison with controls. Scintigraphy with MIBG allowed the selective in-vivo investigation of postganglionic sympathetic cardiac efferents in patients with autonomic failure, a procedure which was previously confined to post-mortem examination. Conclusion - These findings point to a relevant postganglionic pattern of involvement of the autonomic nervous system (ANS) in Parkinson's disease and autonomic failure.

Nutritional status in acute stroke: undernutrition versus overnutrition in different stroke subtypes

Abstract: Objectives – Nutritional status in the acute stage of stroke has not been properly evaluated in different stroke subtypes. The objective of this study was to investigate the nutritional status of different subtypes of stroke patients. Subjects and methods – We studied 88 female patients with first-ever strokes. Strokes were divided into cerebral infarction (CI, n=67) and intracerebral hemorrhage (ICH, n=21). We measured the nutritional status of the patients in the acute stage of stroke with the use of 8 parameters including 3 biochemical and 5 anthropometric ones. These variables were assessed in stroke patients and 120 age-matched controls, and were compared with each other. Results – In the acute stage of stroke, undernourishment was significantly (P=0.000) more prevalent in the ICH group (62%) than in the CI group (25%) or controls (13%). On the other hand obesity was present in 10%, 24% and 17% in patients with ICH, those with CI, and controls, respectively, which was not significantly different (P=0.461). Only abdominal skinfold thickness was significantly greater in patients with CI than in those with ICH or controls. Conclusions – Our results illustrate that undernourishment is prevalent in acute stroke patients, significantly more so in patients with ICH than in those with CI. Stroke patients, especially those with ICH, should receive special nutritional intervention starting immediately after admission.

Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study

Abstract: Objectives - To evaluate the efficacy and safety of one single intravenous methylprednisolone (IVMP) pulse therapy in myasthenia gravis. Material and methods - We performed a double blind placebo controlled study (2+2 g IVMP vs placebo) in patients with moderate MG. Results - A mean increase in muscle function of 27 points was found in the treatment group after one IVMP pulse as compared with a 0.7 point increase in the placebo group (P<0.01). In the IVMP group 8 of 10 patients showed a positive treatment response. The mean duration of improvement after IVMP was 8 weeks (range 4-14 weeks). No severe side effects were found. Acetylcholine receptor antibody concentrations were unchanged in spite of the positive treatment response. Conclusions - We conclude that a single IVMP treatment is efficacious and safe in the treatment of moderate MG.

Postoperative multichannel magnetoencephalography in patients with recurrent seizures after epilepsy surgery

Abstract: Objective - Assessment of usefulness of magnetoencephalography (MEG) as a novel non-invasive technique in the diagnostic evaluation of patients with recurrent seizures after unsuccessful epilepsy surgery. Material and methods - Seventeen patients in whom epilepsy surgery had failed underwent reevaluation by means of MEG in addition to standard presurgical investigations (EEG, MRI, SPECT, and neuropsychologic testing). Results - Source analysis of interictal epileptic MEG discharges revealed dipole localizations immediately adjacent to the borders of previous resection in 10 of 17 patients. Standard non-invasive presurgical evaluation suggested epileptogenicity over the general area of previous resection in all patients, but did not provide any detailed spatial localizing data. Invasive EEG recordings confirmed the MEG focus localization in all of 5 patients who were selected for reoperation. Second operation at the site of previous resection achieved complete seizure control in 3 and cessation of tonic-clonic seizures in 1 of these patients. Conclusion - MEG may provide useful information in the diagnostic reevaluation of postoperative epileptic patients in whom skull and dura defects produce a breach effect which alters non-invasive and invasive EEG.

Multiple sclerosis in Móstoles, central Spain.

Abstract: Objectives - Until relatively recently southern Europe was regarded as having a medium to low multiple sclerosis prevalence, of about 20 or less per 100,000. However, recent studies in Sardinia, Sicily, continental Italy, Cyprus and Spain have yielded higher MS prevalence rates, between 32 and 102.6 per 100,000. We present the results of a prevalence study of MS in the municipality of M6stoles, central Spain. Material and methods - To ascertain the prevalence of multiple sclerosis in Mostoles (195,979 inhabitants), an intensive study was undertaken using several sources of information. We used the Poser criteria in diagnosis. Results - There were 85 patients (53 women and 32 men) classified as definite or probable, prevalence 43.4/100,000 (95% CI, 34.7 to 53.7). The incidence rate was 3.8/100,000/year (95% CI, 2.7 to 5.3) in the last 5 years. Mean age on prevalence day was 38.8±10.9 years. Mean age at onset was 31.7±9.3 years. Mean interval between initial symptoms and diagnosis was 1.7 years. Mean duration of disease was 7.6±6.1 years. Overall, 70.6% had a relapsing-remitting course, 18.8% had a primary progressive and 10.5% had a secondary progressive. Mean EDSS score was 2.7±1.9. Conclusion - The Mostoles study confirms the conclusions of previous smaller population studies that Spain is a moderately high or medium MS risk zone.

Decreased myocardial 123I-MIBG uptake in Parkinson's disease.

Abstract: We studied myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation in 12 patients with Parkinson's disease (PD). MIBG is an analog of norepinephrine (NE) and a tracer for sympathetic neuron integrity and function. MIBG uptake of the myocardium was significantly lower in PD than in controls. The heart to mediastinum ratio (H/M) was calculated by using the average count per pixel for the heart and mediastinum. In PD, H/M was lower than in controls (P<0.0001), while the washout ratio of the heart was higher (P<0.001). A decrease in myocardial accumulation of MIBG was observed in the early stage of PD. This suggests that the measurement of MIBG may help the diagnosis of early PD, and the causative factor underlying in PD may be operating the NE neuron as well as dopamine neuron.

Man-in-the-barrel syndrome caused by cervical spinal cord infarction.

Abstract: Acute brachial diplegia with normal findings of the legs, "man-in-the barrel" (MIB) syndrome, is generally thought to be caused by bilateral supratentorial brain lesions of the prerolandic cortical and subcortical area. We report 1 patient with a sudden onset of MIB syndrome with no supratentorial lesion but a hemodynamically induced atypical anterior spinal cord infarction after unilateral vertebral artery dissection. Thus, in MIB syndrome an infratentorial lesion site, including the cervical spinal cord, should also be considered.

Metabolic causes of recurrent rhabdomyolysis

Abstract: Objectives - The aim of the study was to evaluate the biochemical causes of recurrent rhabdomyolysis in Finland. Material and methods - We examined 22 patients with recurrent rhabdomyolysis, and 26 patients with one episode of rhabdomyolysis or other symptoms compatible with metabolic myopathy. Muscle histopathology and activities of phosphorylase (PHRL) (total and active), phosphofructokinase (PFK), carnitine palmitoyltransferase (CPT) and myoadenylate deaminase (MAD) were studied. The limit of enzyme deficiency was defined as enzyme activity less than 5% of the mean of the control subjects. Results - We found 4 patients with muscle PHRL deficiency, 1 patient with PFK deficiency and 1 patient with evidence of phosphorylase kinase deficiency. One patient had Becker's muscle dystrophy, 2 patients had unspecified dystrophies, 1 patient had Miyoshi myopathy, and 1 patient had a form of mitochondrial encephalomyopathy (MELAS). Conclusion - Enzyme defects were found in 23% of the patients with recurrent rhabdomyolysis. Other muscle diseases, muscular dystrophies or myopathies, were detected in 18% of these patients, emphasizing the value of clinical and histopathological examination of patients with previous rhabdomyolysis.

Stroke risk factors and development of collateral flow in carotid occlusive disease.

Abstract: BACKGROUND AND PURPOSE Blood flow through collateral vessels compensates for reduced blood flow through stenotic or occluded extracranial carotid arteries. Previous studies have shown that extent of collateral flow influences likelihood of stroke and its outcome. Here we analyzed the relationship between stroke risk factors (hypertension, coronary artery disease, diabetes mellitus, tobacco smoking and hypercholesterolemia) and number of patent intracranial collaterals detected by transcranial Doppler ultrasonography. SUBJECTS AND METHODS We studied 182 patients with various degrees of angiography proven unilateral stenosis of the internal carotid artery. Contribution of the anterior and posterior communicating arteries to the perfusion of the cerebral hemisphere on the side of the stenosis or occlusion was evaluated by a series of compression tests performed during continuous insonation of the middle cerebral artery. The number of detected collateral vessels was correlated with analyzed stroke risk factors. RESULTS Subjects with stenosis more than 75% or occlusion of the internal carotid artery had a higher frequency of two major intracranial collateral vessels (P< or =0.01 and P< or =0.001, respectively). Hypertensive patients with stenosis more than 75% or total carotid occlusion were more likely to have only a single collateral vessel than patients without hypertension (P< or =0.01 and P< or =0.05, respectively). Other risk factors did not influence the patency of preformed collateral vessels. CONCLUSIONS Hypertension hindered the development of preformed intracranial collateral vessels in our patients with carotid occlusive disease.

Prognostic predictors of acute transverse myelitis.

Abstract: Introduction – The role of clinical, MRI and neurophysiological parameters in predicting the outcome of acute transverse myelitis (ATM) is reported. Materials and methods – Thirty-one patients with ATM were subjected to clinical, MRI, somatosensory and motor evoked potential studies in both upper and lower limbs and concentric needle electromyography. The outcome was defined at the end of 6 months into poor (Barthel Index score <12) and good (<12). The relationship of various prognostic variables was evaluated by biserial correlation coefficient and stepwise discriminant analysis. Results – The mean age of the patients was 30.4 years and 7 were females. Fifteen patients had good and 16 had poor outcome. The variables significantly related to the outcome included severity of weakness, denervation on EMG and unrecordable central motor conduction time to tibialis anterior (CMCT-TA) and tibial somatosensory evoked potentials (SEPs). Combination of severity of weakness and EMG had 90.3% predicting power. Addition of central sensory conduction time (CSCT) or central motor conduction time (CMCT) did not offer further advantage. Conclusion – Severity of weakness and denervation on EMG are most useful for predicting the outcome of ATM at 6 months although in early stage motor and somatosensory evoked potentials may be used instead of EMG.

Pulsed methylprednisolone induces a reversible impairment of memory in patients with relapsing-remitting multiple sclerosis

Abstract: Objective – Chronic administration of corticosteroids has been reported to selectively impair explicit memory in systemic diseases without central nervous system involvement. Our aim was to verify that a short course of pulsed intravenous methylprednisolone (IVMP) administered for the treatment of a relapse impairs cognitive functions in relapsing-remitting multiple sclerosis (RRMS) patients and to determine whether this impairment is reversible. Material and methods – Neuropsychological evaluations were made before the start of treatment, and 7 and 60 days after the end of treatment in 14 RRMS patients. The neuropsychological battery was also administered to 12 controls matched for age, sex and years of education. Results – RRMS patients performed worse than the controls at their baseline evaluation for a variety of neuropsychological tasks. IVMP administration induced a selective impairment of explicit memory which completely recovered 60 days after treatment. Conclusions – In RRMS patients, IVMP induces a selective and reversible impairment of explicit memory.

Regional increases in [11C]flumazenil binding after epilepsy surgery.

Abstract: Introduction - Animal experiments suggest that epileptic seizures alter the expression of mRNA for neuro-receptors. PET measurements with [ 11 C]flumazenil show that patients with partial seizures have a reduced density of benzodiazepine (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for seizure activity, the so called projection areas. Recent data suggest that the degree of BZ receptor reduction in ER is correlated to seizure frequency. We therefore hypothesized that seizure activity can alter the BZ receptor binding, and that some of these changes could normalize when the seizures disappeared. Methods - In 4 patients whose seizures were generated by mesial temporal lobe structures, BZ receptor density was measured with [ 11 C]flumazenil PET before, and 1 year after the epilepsy surgery and cessation of seizures. By use of a computerized anatomical brain atlas the same regions were analyzed in both PET scans, and the results related to data from 7 healthy controls. Results - Presurgical PET scans showed reductions in BZ receptor density in the epileptogenic region and some of its primary projection areas. Other cortical regions had normal values. Postsurgically, the calculated BZ receptor density normalized (29±17% increase) in several of the affected projection areas, whereas the values in other cortical regions remained unaltered. Conclusion - Regional reductions in BZ receptor density may be dynamic and related to seizures. The present preliminary observations encourage further studies on seizure-related changes in regional receptor binding in humans.

Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients.

Abstract: OBJECTIVES To investigate the in vivo effect of corticosteroid pulse therapy on immunocompetent cells in 18 patients given methylprednisolone to treat an acute episode of MS. MATERIAL AND METHODS Blood was sampled before and after 3 days of methylprednisolone administration at doses of 1 g/day. Lymphocyte subtyping was performed and whole blood cell cultures were used to measure the cytokine producing capacity for interleukin-1 (IL-1), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha). In addition, serum levels of the immunoglobulin classes IgG, IgA and IgM were determined. RESULTS Before treatment, production of IL-1 was significantly increased in MS patients as compared to healthy controls. After therapy, production of all cytokines was significantly decreased, whereas there were significant increases in the numbers of monocytes, neutrophils and T and B lymphocytes. Treatment had no effect on serum immunoglobulin levels. CONCLUSION An important mechanism for the antiinflammatory effect of corticosteroids in MS results from a suppression of the activation of the peripheral immune compartment through inhibition of cytokine production and lymphocyte endothelial adhesiveness.

A single subtype of Epstein–Barr virus in members of multiple sclerosis clusters

Abstract: Objectives – Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein–Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelso. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts. Materials and methods – Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsto cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals. Results – We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjelso cluster all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer's exact test P=0.0047), and also compared to all non-clustered individuals studied (P=0.017). Conclusion – Infection with the same subtype of EBV links together the 8 persons from the Fjelso cluster who later developed MS. This finding adds to the possibility that development of MS is linked to infection with EBV.

Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development.

Abstract: OBJECTIVES It was shown previously that low-Mg2+-induced epileptiform activity in rat entorhinal cortex slices changes with time from a pattern of serial seizure-like events (SLEs) to a state of continuously recurring epileptiform activity Valproic acid blocked the early SLEs but not the late activity It was proposed that the late activity is a model for pharmacoresistant status epilepticus since it was also refractory to phenytoin, carbamazepine, phenobarbital, and midazolam In the present study, it is demonstrated that phenytoin (50 microM, n=6), phenobarbital (150 microM, n=7), and midazolam (50 microM, n=5) were able to block the early SLEs but not the late activity at the same concentrations Carbamazepine (50 microM) reduced the duration of the SLEs from 21 +/-5 s to 4+/-3 s (P<001), the interictal interval from 123+/-27 s to 27+/-19 s (P<001), the SLE-associated rise of [K+]o from 77+/-05 mM to 57+/-08 mM (n=4, P<005), and the spread of the SLE between entorhinal cortex and neocortex from 40+/-06 s to 08+/-01 s (n=4, P<005) Lower concentrations of phenytoin (5 and 10 microM, n=5), carbamazepine (10 microM, n =6), and phenobarbital (50 microM, n = 4) had no effect In conclusion, the hypothesis is supported that low-Mg2+-induced epileptiform activity in rat entorhinal cortex is an in vitro model for the transition from pharmacosensitive to pharmacoresistant status epilepticus

Low dosage clozapine effects on L-dopa induced dyskinesias in parkinsonian patients

Abstract: Objectives – The aim of this study was to investigate the clinical efficacy of clozapine, an atypical neuroleptic, on L-dopa induced dyskinesias of Parkinson's disease. Material and methods – In an open study, a group of 10 PD patients was treated with low dosage clozapine (mean 30 mg/day) for a 4-month period and L-dopa dyskinesias were evaluated in basal conditions and during clozapine treatment after the usual morning dose of clozapine. We utilized the AIMS for evaluation of dyskinesias and UPDRS for the assessment of motor performances. Results – Clozapine produced a significant (P < 0.05) reduction of dyskinesias 1 week after the therapy onset. This effect was more pronunced at the end of the 2nd week and remained stable through the following months. We did not observe significant variations of motor performances. Conclusion – A low dose of clozapine appears to be beneficial for patients with L-dopa induced dyskinesias that do not respond to other drugs and therapeutic measures.

Temporal lobe epilepsy visualized with PET with 11C-L-deuterium-deprenyl--analysis of kinetic data.

Abstract: Objectives - The purpose of the study was to develop a simplified method for the acquisition and analysis of data from positron emission tomography (PET) using the ligand C-L-deuterium-deprenyl. This is motivated by an increased interest in methods to characterize gliosis in neurodegenerative diseases and epilepsy, which can be defined due to an increased expression of the enzyme MAO-B. Methods - Seven patients with temporal lobe epilepsy were investigated with PET. The tracer kinetics in different brain structures was recorded and analyzed using different models with and without a plasma input function. The derived values were correlated to literature values of 3 H-deprenyl binding in frozen sections from normal human brains Results - A good correlation was seen between in vivo binding and in vitro data, with the correlation being equally good irrespective of whether metabolite corrected plasma or modified cerebellar uptake values were used as input function. The epileptic lobe was, compared to non-epileptic, characterized by a lower initial distribution and an enhanced late accumulation of the tracer. With the applied method, it was possible to correctly identify the epileptic side in all 6 unilateral patients and 1 probable bilateral case. Conclusions - PET with C-L-deuterium-deprenyl gives a good correlation between calculated in vivo binding and MAO-B activity. The analysis can be simplified and blood sampling avoided if modified cerebellar time-activity data is used as a reference. Separate images of distribution volume and MAO-B binding can be generated.

Herpes simplex virus type 2 DNA detected in cerebrospinal fluid of 9 patients with Mollaret's meningitis

Abstract: We present clinical and virological data on 9 patients, 7 women and 2 men aged 31-56 years, with recurrent aseptic meningitis (Mollaret's meningitis). Polymerase chain reaction detected Herpes simplex virus type 2 DNA in cerebrospinal fluid samples from all patients collected during their latest attacks of meningitis. Six patients had no history of genital herpes. Only 1 patient was offered prophylactic antiviral treatment during the study period (45 months).

Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis.

Abstract: Objective - The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. Material and methods - Cerebrospinal fluid and serum samples from 69 paticnts with possible first attacks of MS, 50 patients with clinically definite MS (CDMS), and 118 patients with other neurological diseases (OND) were analyzed. IgG and FLC oligoclonal bands were detected by isoelectric focusing and immunoperoxidase staining. Results - Intrathecal synthesis of IgG, kappa FLC, and lambda FLC oligoclonal bands, respectively, was seen in 92%, 92%, and 86% of MS patients; in 61%, 62%, and 64% of patients with possible first attacks of MS; and in 3%, 3%, and 8% of the patients with OND. In control patients without IgG synthesis intrathecal lambda FLC synthesis was more common than kappa FLC synthesis (P=0.03). Conclusion - Kappa FLC detection proved as useful as IgG analysis for the laboratory diagnosis of MS whereas the presence of intrathecal lambda FLC synthesis was less specific.

Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population

Abstract: Introduction - The regulatory role of apolipoprotein E in lipid transport and metabolism was utilized to investigate the allelic association between the apolipoprotein E4 (apoE4) allele and vascular dementia (VD) in a selected sample of Hungarian patients with multiple deep subcortical infarcts and leukoaraiosis. Material and methods - Thirty-four Caucasian VD cases and 79 healthy control probands were involved in this study according to the criteria of ICD-10 and NINDS-AIREN International Workshop Diagnostic Criteria. The genomic DNA was isolated from whole blood and the apoE alleles were determined by polymerase chain reaction. Results - The E2, E3 and E4 allele frequencies in the VD group were 5%, 76%, and 19%, respectively; and significant (P<0.03) differences were found in comparison with the data on the healthy controls (E2, 6%; E3, 87%; E4, 8%). The apoE4 allele frequency was intermediate between HC and Alzheimer's dementia group (28%). Conclusion - These results indicate that the apoE4 allele could be a risk factor not only for certain primary degenerative, but also for vascular dementias.

Is the mitochondrial DNA involved in determining susceptibility to multiple sclerosis

Abstract: An increasing number of case reports on Leber's hereditary optic neuropathy (LHON) associated mitochondrial (mt)DNA point mutations in patients with multiple sclerosis (MS) raised the possibility that mitochondrial determinants may contribute to genetic susceptibility to MS. These observations prompted many laboratories including ours to perform comprehensive sequencing or large scale screening of the mtDNA in MS patients. Here we review the available data arguing for or against a mitochondrial hypothesis for MS. We conclude that pathogenic mtDNA point mutations are not associated with typical forms of this disease. A very small subgroup of MS patients, usually with prominent optic neuritis (PON), may carry pathogenic LHON mutations. This partial overlap between the two diseases may be related to the association of MS with a mtDNA haplotype (a set of mtDNA polymorphisms) within which pathogenic LHON mutations preferentially occur.

Sex‐related differences in human cerebral hemodynamics

Abstract: Objectives - To identify possible inter-hemispheric sex-related cerebral hemodynamic differences at rest, in healthy subjects by transcranial Doppler (TCD). Subjects and methods - Mean flow velocity (MV) was recorded by TCD in 96 (48 males, 48 females) right-handed volunteers. Mean age was similar in males and females, distribution of age-groups by sex was similar, too. Results - Examining by sex MV values in each basal artery, left middle cerebral artery (MCA) showed a statistically significant difference (53.5±8.2 cm.s -1 in males versus 58.5±10.4 cm.s -1 in females, P=0.005, one-way ANOVA). Multiple regression models show a significant correlation between age and MV on each side, while sex correlates with MV on the left side. Conclusion - A sex-dependent hemispheric difference in MV in the left MCA at rest (females>males) in the younger population subgroup was identified. These data support recent observations on anatomical differences between sexes, referring a proportionally larger Broca area in females compared to males.

CAG repeat expansions in patients with sporadic cerebellar ataxia.

Abstract: CAG repeat expansions cause spinocerebellar ataxia type 1 (SCA1), SCA2, SCA3, SCA6 and dentatorubral-pallidoluysian atrophy (DRPLA). So far these expansions have been examined mainly in ataxia patients with a family history. However, some sporadic cases with SCA have recently been reported. To elucidate the frequency and characteristics of sporadic SCAs, we screened 85 Japanese ataxia patients without a family history for the SCA1, SCA2, SCA3, SCA6 and DRPLA mutations. As a result, 19 patients (22%) were found to have expanded CAG repeats. Among sporadic SCAs, the SCA6 mutation was most frequently observed. The sporadic SCA6 patients had smaller CAG repeats and a later age of onset than SCA6 patients with an established family history. We also identified one father-child pair in which intermediate sized CAG repeats expanded into the SCA2 disease range during transmission. These findings suggest that patients with ataxia even without a family history should be examined for a CAG repeat expansion.

Echocontrast enhanced transcranial colour-coded duplex offers improved visualization of the vertebrobasilar system

Abstract: Objectives - By means of transcranial colour-coded duplex sonography (TCCD) through the foramen magnum, the intracranial vertebral artcries (VAs) and the basilar artery (BA) can be investigated. In this study we evaluated the additional diagnostic value of echocontrast administration in patients with an insufficient pre-contrast TCCD investigation of the vertebrobasilar system. Material and methods - In 22 patients the intracranial VAs and the proximal, middle and distal BA were evaluated before and after the application of 4 g of the echocontrast agent Levovist®. The length of the different vessel segments visualized on colour modc before and after echocontrast, and the diagnostic benefit and the diagnostic confidence were assessed. Results - Echocontrast enlarged in cach vessel segment the length that could be visualized. Using echocontrast, in 5/22 patients (23%) definite and probable pathological findings unnoted in the native scans were detected. In 12 additional paticnts (55%) the investigator and the clinician became confident with thc vascular diagnosis by echocontrast to a degree that angiography could be avoided. In only 3/22 patients (14%) no gain and in 2/22 paticnts (9%) an insufficient diagnostic gain was noted. Conclusions - Our study demonstrates that echocontrast provides effective Doppler signal enhancement and considerably increases the diagnostic gain of TCCD in the intracranial vertebral and basilar vasculature.

Proton magnetic resonance spectroscopy of the brain in three cases of Rett syndrome: comparison with autism and normal controls

Abstract: Rett syndrome (RS) is a clinically defined disorder characterized by autistic behavior, and cognitive and motor skill loss early in life. We performed 1H-MRS of the brain in 3 cases of RS in comparison with in autism and controls. The older patient with RS demonstrated decreased N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine (Cr) ratios when compared with the autism and control groups, whereas the younger patients did not demonstrate these decreased metabolite ratios. The Cho/Cr ratio did not differ among Rett syndrome, autism and controls. Since the clinical stage did not differ among the 3 cases of RS, it was suggested that NAA was decreased with increasing age and was not related with the clinical stage of RS. The NAA/Cho, NAA/Cr and Cho/Cr ratios did not differ between autism and controls. The present data suggest that there may be a secondary degenerative process of late onset in RS, which pathophysiologically differs from autism.

An epidemiological study of multiple sclerosis in central Sardinia, Italy

Abstract: Objectives – To verify morbidity estimates in central Sardinia, Italy. Methods – A prevalence study was performed in the province of Nuoro, Central Sardinia, which has a population of 273,768 inhabitants (135,383 men and 138,385 women). A complete enumeration approach was adopted by using all possible case-collection sources. Results – On prevalence day, December 31, 1993, 394 subjects (124 men and 270 women) living in the study area were known to suffer from definite and probable MS, giving a crude prevalence rate of 143.9 cases per 100,000 people, 91.6 for males and 195.11 for females. The crude prevalence estimated on December 31, 1985, based on 282 MS cases alive in the study area, was 102.94 per 100,000. Conclusion – This study reinforced central Sardinia's position as a high and rising prevalence area for MS.

The prevalence of multiple sclerosis in the hungarian city of szeged

Abstract: Objectives - The aim of this study was to determine the prevalence of multiple sclerosis in a population in South Hungary. Methods - The diagnosis was established with the aid of the Poser diagnostic criteria and the degree of physical disability was determined on the Kurtzke expanded disability status scale (EDSS). The present medical state (EDSS score) was determined from outpatient clinical control tests. The prevalence, the average age at onset of the disease and the proportions of the various clinical forms were calculated, and the patients' disability status was estimated. Results - In 1996, the prevalence was 65/100,000, and the incidence from January 1, 1995 through December 31, 1996 was 7/100,000/year. Discussion - During a period of 2 years, the number of diagnosed patients has almost doubled. The disease can be recognized in an early stage with a minimal neurological deficit. The development of the diagnostics necessitates re-examinations with modern diagnostic procedures. During the last 3 years, the general practitioner system has been reorganized, and the working relationships between the clinic and family doctors have developed considerably. A comparison of the present findings with those in other countries with a similar climate revealed very similar prevalence data.