bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster of Creutzfeldt–Jakob disease in France associated with the codon 200 mutation (E200K) in the prion protein gene
Authors: Chatelain Jacqueline , Delasnerie‐Lauprêtre Nicole , Lemaire Marie‐Hélène , Cathala Françoise , Launay Jean‐Marie , Laplanche Jean‐Louis
Published: March 2003

Between 1992 and 1995, the annual incidence of Creutzfeldt–Jakob disease (CJD) in one of the 96 French départments (adminstrative districts) was found to be about six times higher than the CJD national incidence. Among the 12 definite or probable CJD patients referred during this period within this département, nine originated from a small confined area (30 × 30 km) and seven patients carried the E200K mutation in their prion protein gene (PRNP). Genealogical data showed that these seven cases, together with three other ones previously referred during the 1970–82 period, probably belonged to different branches of the same family which could be traced to the beginning of the eighteenth century. Interestingly enough, all but two patients presented as sporadic cases before the genealogic and genetic studies. To our knowledge, this study is the first describing in France a focal accumulation of CJD associated with the PRNP E200K mutation.
Sumatriptan nasal spray: a dose‐ranging study in the acute treatment of migraine
Authors: Peikert A. , Becker W.J. , Ashford E.A. , Dahlof C. , Hassani H. , Salonen R.J.
Published: March 2003

This multicentre, randomized, double‐blind, placebo‐controlled, parallel group dose‐ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P < 0.01). Also, the 20 mg dose was significantly superior to both the 10 and 5 mg doses at this time point (P < 0.05). The proportion of patients who were headache‐free 120 min after treatment, was also higher following 20 mg (42%) rather than following any other sumatriptan dose (14–24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in patients who had responded to initial treatment was reported by 30–41% of patients who received sumatriptan, compared with 33% of patients in the placebo group. Sumatriptan nasal spray was well tolerated, the incidence of adverse events with each dose of sumatriptan being similar to the placebo (20–27 and 23%, respectively). Apart from bad/bitter taste, the events were comparable with those reported following sumatriptan treatment by other routes of administration.
Inter‐laboratory validation of an ELISA for the determination of serum anti‐ganglioside antibodies
Authors: Willison Hugh J. , Veitch Jean , Swan Anthony V. , Baumann Nicole , Comi Giancano , Gregson Norman A. , IIIa Isabel , Jacobs Bart C. , Zielasek Jurgen , Hughes Richard A.C.
Published: March 2003

Anti‐ganglioside antibodies are frequently sought in the sera of patients with autoimmune peripheral neuropathy, using an enzyme‐linked immunosorbent assay (ELISA) as the principal method for antibody detection. Wide variations in assay performance between laboratores have been reported. In this study, we established a standardized ELISA method between laboratories within the European Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the inter‐laboratory variance in assay performance using both the standardized INCAT method and in‐house local methods. As expected, the inter‐laboratory variances were greater using local methods than using the standardized method, producing titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively, than the true means for these laboratories. Using the standardized method, the within laboratory measurement error accounted for 41% of the inter‐laboratory variation, providing a theoretical upper limit to which technical improvements within laboratories could reduce inter‐laboratory variation. These data describe the intrinsic weaknesses within the widely used ganglioside antibody ELISA methods and reinforce the importance of inter‐laboratory cooperation within this area. Standardized serological reagents used in this study are available from INCAT members.
Reversible F‐wave hyperexcitability associated with antibodies to potassium channels in Isaacs' syndrome
Authors: Tanosaki Masato , Baba Masayuki , Miura Hiroyuki , Matsunaga Muneo , Arimura Kimiyoshi
Published: March 2003

We report a case of Isaacs' syndrome showing F‐wave hyperexcitability which was reversible after either epidural block or plasmapheresis. A 14‐year‐old girl with progressive muscle cramp and myokymia in the legs showed high amplitude, long duration, polyphasic F‐waves after either tibial nerve or peroneal nerve stimulation. Potassium current of PC‐12 cell membrane was suppressed by her serum, IgM of which strongly reacted with proteins of approximately 50 kDa of the lysates of a PC‐12 cell line. After an epidural nerve block with 1 per cent lidocaine 10 ml, the myokymia temporally improved, during which time the hyperexcitable F‐waves became normalized. We treated her with double filtration plasmapheresis, which resulted in remarkable improvement of myokymia; simultaneously, the abnormal F‐waves showed a decrease in amplitude, duration, and in the number of phases. We concluded that there was hyperexcitability of the proximal site of motor fibers in our patient, and possible immune mechanisms gave rise to the myokymia and unusual F‐wave features.
Frontal type dementia preceding amyotrophic lateral sclerosis: a neuropsychological and SPECT study of five clinical cases
Authors: Vercelletto M. , Ronin M. , Huvet M. , Magne C. , Feve J.R.
Published: March 2003

Between 1993 and 1995, we observed five sporadic cases of frontotemporal dementia (FTD) which in all cases preceded the appearance of typical amyotrophic lateral sclerosis (ALS). The FTD rapidly became severe (within 12‐18 months) and the delay between the presumed onset of mental change and ALS was short (12–26 months). The frontal dysfunction was characteristic (disinhibited, jocular, impatient, gluttonous, stereotypical gestures). The language impairment (less talkative, persistent errors, fantastic and semantic paraphasia, neologistic errors, echolalia) was constant. Single photon emission computed tomography (SPECT) with 99 Tcm HMPAO (hexamethyl propylamine oxime) was done at the same time as neuropsychological testing in four cases and showed serious diffuse bifrontal defect, sometimes with less serious internal temporal hypofixation. All patients died with bulbar ALS complications. The total course can last from 14–48 months. Most of the reported cases suggested a relationship between dementia‐ALS and frontal dysfunction. The mechanism underlying dementia‐ALS remains to be solved. Our five cases resemble those reported by Mitsuyama (1993), who suggested that dementia‐ALS has the same clinicopathological entity.
Clinical and molecular analysis of 11 Sicilian SCA2 families: influence of gender on age at onset
Authors: Giuffrida Salvatore , Lanza Sara , Restivo Domenico A. , Saponara Riccardo , Valvo Sebastiana C. , Pira Francesco Le , Salinaro Angela Trovato , Spinella Francesca , Nicoletti Alessandra , Condorelli Daniele F.
Published: March 2003

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of slowly progressive neurodegenerative disorders characterized by gait and stance ataxia, dysarthria and other symptoms of nervous system involvement. ADCA type I is the commonest form and is genetically heterogeneous; several loci have been identified. Spinocerebellar ataxia type 2 (SCA2) has been mapped to chromosome 12, with expanded cytosine‐adenine‐guanine (CAG) repeats being identified as the mutational cause of the disease. We investigated 15 families, all originating from mid‐eastern Sicily, with ADCA type I; molecular studies performed in 12 families showed the SCA2 mutation to be present in 11 of them (91.6%) ‐ the highest occurrence so far reported in the literature. The CAG repeat of the affected alleles varied between 34 and 44 repeats. Age at onset and repeat length revealed an inverse correlation. Mean age at onset was 37.32 ± 16.74 years, and occurred earlier in males than in females. There were no differences in mean CAG repeat units between the sexes. However, a higher instability of CAG repeats was observed for paternal transmission than for maternal transmission. Age at onset and anticipation were not related to parental transmission. Our data suggest that in SCA2 an unknown sexlinked factor may play a role in the modulation of toxic effects of the polyglutamine tract.
Immunochemical quantification of glycoconjugates in serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients
Authors: Niebroj‐Dobosz Irena , Janik Piotr , Jamrozik Zygmunt , Kwieciński Hubert
Published: March 2003

Glycoconjugates in the serum of 73 patients with amyotrophic lateral sclerosis (ALS), 21 cases of other motor neuron diseases and 20 healthy controls were determined. Cerebrospinal fluid (CSF) was studied in 64, 7 and 10 of these subjects. respectively. The level of sialic acid containing glycoconjugates, detected by Maakia amurensis agglutinin (M.AA), was decreased in the serum of 61.6% of the ALS patients, while in the CSF it was decreased, on average, in 75% of these cases. Only in single ALS cases was the concentration of these glycoconjugates increased. There was no correlation between the content of MAA‐labelled glycoconjugates both in serum and CSF and the titre of sialic acid containing antiGMI gangliosides. The glycoconjugates, detected by peanut agglutinin (PNA) which recognizes the disaccharide galactose β(1‐3)N‐acetylgalactosamine (GGN), were decreased in the serum of 78.1% of ALS patients, while in CSF they were increased in 54.7% of these cases. There was no correlation between the concentration of PNA‐labelled glycoconjugates both in serum and CSF as well as the titre of antibodies against GGN‐containing anti‐GM1 and anti‐AGM1 gangliosides. Changes in the level of the MAA‐ and PNA‐labelled glycoconjugates, as well as the titre of anti‐GM1 and anti‐AGM1 gangliosides antibodies were not specific for ALS. They were also observed in some cases of other motor neuron diseases. The low level of the lectin‐labelled glycoconjugates in serum and party in CSF of the majority of ALS patients is possibly the consequence of their accelerated clearance and/or specific inactivation by the formation of immune complexes or epitope binding. Degeneration of neurons and muscle cells could also be responsible. The relatively low incidence of high anti‐glycolipids antibodies titre may be, at least partly, connected with the low concentration of the appropriate antigens. The increased content of PNA‐labelled glycoconjugates in the CSF of the majority of ALS patients, together with the low incidence of high titre of antibodies against the appropriate glycolipids, could indicate that in CSF this lectin binds to the GGN epitope of glycoproteins rather than to the GGN epitope of glycolipids.
Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis
Authors: Paź Aleksandra , Fiszer Urszula , Zaborski Jacek , Korlak Janina , Czlonkowski Andrzej , Czlonkowska Anna
Published: March 2003

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing‐remitting or relapsing‐progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 agematched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence‐conjugated murine monoclonal antibodies. The analysis was performed with three‐color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly‐5), CD45; LPS‐R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA‐2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin β2 subunit, associated with CD11a (CD11a/CD18, LFA‐1 αLβ2) and CD11b (CD11b/CD18, Mac‐1,CR3, αMβ2), CD18; αL, α subunit of integrin LFA‐1 (αLβ2, CD11a/CD18), CD11a; αM, α subunit of integrin Mac‐1 (CR3, αMβ2, CD11b/CD18), CD11b; ICAM‐1 (intercellular adhesion molecule), CD54; H‐CAM, Hermes antigen, Pgp‐1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T‐cell receptor γδ. TCR γδ. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54+and CD11a+CD54+ lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on lymphocytes, and higher percentage CD54+and CD11a+CD54+ lymphocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.
Linguistic impairment after right cerebellar stroke: a case report
Authors: Gasparini Marina , Piero Vittorio Di , Ciccarelli Olga , Cacioppo Maria Maddalena , Pantano Patrizia , Lenzi Gian Luigi
Published: March 2003

Increasing evidence suggests the involvement of the cerebellum in non‐motor functions. We describe a patient who presented speech deficits after a right cerebellar infarction without other cognitive impairments. 99mTc‐HMPAO singlephoton emission computed tomography showed a marked hypoperfusion in the right cerebellar hemisphere, but did not show crossed cerebellar‐cerebral diaschisis. The absence of neuroradiological evidence of structural supratentorial lesions supports the cerebellar role in modulating not only the motor system, but also higher order functions.
A patient with multiple sclerosis and Down's syndrome with a rare paroxysmal symptom at onset
Authors: Solaro C. , Uccelli M. Messmer , Mancardi G. L.
Published: March 2003

Down's syndrome (DS) is often associated with autoimmune diseases, although an association with multiple sclerosis (MS) has not been previously reported. A 49‐year‐old male with DS experienced progressively worsening gait and bladder dysfunction. Following Poser criteria, the patient was diagnosed with laboratory‐supported definite MS. Ten days following diagnosis the patient experienced dysestetic paroxysmal pain at the pelvic level (an uncommon complaint in MS) which was initially addressed with carbamazepine, resulting in mid relief and adverse effects consisting of increased motor deficit and decreased daytime alertness. A titration combination of lamotrigine and gabapentin, two relatively new antiepileptic drugs which have been utilized individually for a number of neurological symptoms, resulted in significant reduction in pain frequency and intensity, with no adverse effects. This case study presents details of the first reported association of DS and MS, between which the pathogenetic relationship remains unclear. The presence of a rare symptom complaint in MS, as well as the effective combination of lamotrigine and gabapentin for treating this symptom, without adverse effects is an additional interesting aspect of this case.
Generalized freezing in Hallervorden‐Spatz syndrome: case report
Authors: Guimarães João , Santos J. Vale
Published: March 2003

We report the case of a female patient who was exhibiting slowly progressive, severe, generalized freezing of voluntary movement and disequilibrium. Brain magnetic resonance imaging showed a very low signal intensity in both pallidal nuclei, with a high signal intensity in the central portion, the so called ‘eye‐of‐the‐tiger’ sign. Despite the unusual clinical features, we believe that this is a case of Hallervorden‐Spatz syndrome, although without neuropathological examination we were unable to confirm the diagnosis with certainty. This case further demonstrates the complex role of the pallidum in voluntary movement.
Neurological and electrophysiological examinations on three groups of workers with different levels of exposure to mercury vapors
Authors: Urban Pavel , Lukáš Edgar , Nerudová Jana , Čábelková Zdena , Cikrt Miroslav
Published: March 2003

The authors performed neurological, visual evoked potentials (VEP) and electroneurography (ENG) examinations on three groups of workers with occupational exposure to mercury vapors (Hg0), and on a control group. The exposure of dental professionals (n= 36) was mild, that of chloralkali plant workers (n= 36) was intermediate, and that of workers from mercury works (n= 77) was very high. Symptoms and signs of micromercurialism were observed only in the group with the highest exposure to Hg0. In comparison with the control group, a shortening of VEP latency and a decrease in amplitude were found in the exposed groups. The VEP changes correlated with Hg0 excreted in urine after administration of a chelating agent — sodium 2,3‐dimercapto‐1‐propan sulfonate (DMPS). The frequency of abnormal VEP results increased with increasing levels of exposure. ENG changes were observed only in the group with the highest exposure to Hg0. An isolated decrease of sural nerve conduction velocity was observed in 18% of total workers. In 70% of the cases, this was associated with an abnormality in VEP. The combination of a decrease in sural nerve conduction velocity and an abnormality of VEP seems to be a characteristic pattern of electrophysiological changes in persons exposed to mercury vapors.
Interleukin‐12 is detectable in sera of patients with multiple sclerosis — association with chronic progressive disease course?
Authors: Heesen Christoph , Sieverding Frank , Schoser Benedikt Gustav Heinrich , Hadji Bijan , Kunze Klaus
Published: March 2003

Multiple sclerosis (MS) is widely accepted as a systemic T‐cell‐mediated autoimmune disease with a T‐helper type‐1 (TH‐1) profile of cytokine production. We addressed the question whether interleukin‐12 (IL‐12), as a central mediator of TH‐1‐cell activities, is detectable in sera of MS patients, and if there is any association with disease activity. We analysed 171 sera of patients with MS and meningitis, and healthy controls. IL‐12 p40 protein was detectable at low levels in MS patients (median 43 pg/ml) and controls (median 49 pg/ml.) Analysing different disease courses and activities, a significant elevation in stable primary progressive MS cases compared with controls (median 66 pg/ml) was found. IL‐12 p40 protein was not detectable in cerebrospinal fluid probes of 10 patients. We conclude that the function of IL‐12 in MS depends on expression and degradation of the different proteins. These could act proinflammatory as well as limiting the disease process.
Developmental dyslexia: atypical cortical asymmetries and functional significance
Authors: Robichon F. , Levrier O. , Farnarier P. , Habib M.
Published: March 2003

Using brain magnetic resonance imaging, we measured in 16 young developmental dyslexic adults and 14 age‐matched controls cortical asymmetries of posterior language‐related areas, including Planum temporale and parietal operculum cortical ribbon, and of the inferior frontal region related in the left hemisphere to speech processing. In addition, we assessed the sulcal morphology of the inferior frontal gyrus in both groups according to a qualitative method. The dyslexic subjects also performed specific tasks exploring different aspects of phonological and lexical–semantic processes. Results showed that: (1) contrary to most results reported in the literature, there is a lack of any morphological difference relative to Planum temporale asymmetry between the two groups; (2) there are significant differences between dyslexic and control subjects relative to frontal areas; (3) concerning the parietal region, there is a more asymmetrical pattern towards the left side in dyslexic subjects than in controls; and (4) relations in dyslexic subjects between parietal asymmetry coefficient and the level of performance in a phonological task have a particular reliance on verbal short‐term memory, frontal asymmetry and performance in a non‐word reading task. Considering these results it is suggested that phonological segmentation skills may relate to frontal lobe morphology, while phonological memory‐based impairment in people with dyslexia may rather relate to parietal lobe morphology.
Unexpectedly severe sleep and respiratory pathology in patients with amyotrophic lateral sclerosis
Authors: Barthlen G. M. , Lange D. J.
Published: March 2003

Daytime fatigue and sleep disturbance are frequent complaints in patients with amyotrophic lateral sclerosis (ALS). However, polysomnographic data are sparse. Nocturnal respiratory insufficiency may occur despite nearly normal daytime pulmonary function. We describe the clinical presentation and polysomnographic findings in two patients with clinically and electrophysiologically confirmed ALS with minimal weakness but excessive daytime sleepiness. Polysomnography in the first patient showed a respiratory disturbance index of 43.5, and profound oxygen desaturations to 62%. The second patient had prolonged periods of hypoventilation, with oxygen saturations oscillating between 86 and 83%. Both patients showed severe sleep maintenance insomnia with a sleep efficiency < 40% and frequent arousals while asleep. Application of continuous positive airway pressure (CPAP) restored normal nocturnal ventilation, blood oxygenation and sleep parameters in the first patient; compliance, however, was poor. The second patient was unable to tolerate CPAP. We conclude that ALS patients with excessive daytime sleepiness or insomnia should undergo polysomnography to adequately diagnose nocturnal respiratory insufficiency and sleep disturbance. Compliance with treatment, however, may be poor.
Researching a differential impairment of frontal functions and explicit memory in early Parkinson’s disease
Authors: Farina E. , Gattellaro G. , Pomati S. , Magni E. , Perretti A. , Cannatà A. P. , Nichelli P. , Mariani C.
Published: March 2003

An impairment at tasks sensitive to frontal lobe damage has been repeatedly reported in Parkinson’s disease, but the exact nature of these deficits has not yet been clarified. Similarly, deficits of visuo‐spatial functions have been frequently observed, but it is still debated whether verbal and visuo‐spatial memory can be differentially affected. In this study we have compared the performance of 20 mild Parkinson’s disease patients (I–II Hoehn and Yahr stage) and 18 matched normal controls, at tasks assessing frontal functions and explicit memory.

We detected a selective deficit in set shifting and maintaining, without impairment in categorization and set formation. The lack of a selective increase in perseverative errors might indicate that perseverations either measure something different from set shifting or that they do not represent an index sensitive enough to set shifting impairment.

Parkinson’s disease patients were also significantly impaired at Raven’s Progressive Matrices, a task assessing both frontal and visuo‐spatial aspects. However, they did not show any differential impairment of visuo‐spatial memory. Indeed, despite a trend of lower performance in visuo‐spatial learning, memory performance of Parkinson’s disease patients was significantly different from that of controls only at a free recall test which involved both verbal and visuo‐spatial memory.

We suggest the exploration of set shifting and maintaining to detect ‘frontal’ deficits in mild Parkinson’s disease. We argue that Raven’s Progressive Matrices is a valuable task for detecting subclinical cognitive deficits in Parkinson’s disease, even if it does not show a specific profile of impairment in these patients. According to our results, a differential evaluation of verbal vs. visuo‐spatial memory is not necessary in clinical practice, whilst free recall confirms its usefulness to detect subclinical impairments of memory functions.
Acute neurological stroke care in Europe: results of the European Stroke Care Inventory
Authors: Brainin M. , Bornstein N. , Boysen G. , Demarin V.
Published: March 2003

Following the 1997 Recommendations of the EFNS Task Force on Acute Neurological Stroke Care (European Journal of Neurology, 1997: 4:435–441) a European Inventory was undertaken to assess the development of acute stroke care in the EFNS member countries and to give an estimate of the needs based on 1997 data.

All 30 members of the EFNS Stroke Scientist Panel were asked to complete a questionnaire on acute stroke epidemiology as well as acute stroke care in their country. Data were based either on national surveys, hospital statistics, or estimates given on the basis of extrapolation of regional studies, or other defined sources. Specialist estimates were also taken into account where no other data source was available.

Data from 22 countries were received and referred to almost one million strokes occurring per year in a population of over 500 million. Most epidemiological data confirmed an east–west gap known from previous studies. These included rates that, in eastern countries, were higher for incidence, stroke as a leading cause of death, and 30‐day case‐fatality, and rates that were lower for overall hospitalization or availability of CT scanning. East–west differences were not seen for the total number of acute stroke units or the number of acute stroke units set up within neurological hospital departments, nor for most other quality indicators of acute stroke care with the exception of technological standards in some countries.

The higher rates for 30‐day case‐fatality in eastern Europe (mostly above 20%) compared with western Europe (mostly below 20%) are probably caused by a case mix with more severe ischemic strokes and a higher percentage of cerebral haemorrhages admitted for acute care in eastern Europe. This is probably due to the higher prevalence of the most common risk factors for stroke in these countries which tend to result in more severe strokes. This, therefore, underlines the need for stroke prevention programmes especially in eastern Europe. This epidemiological east–west gap is not reflected by most quality indicators for acute stroke care, e.g. total number of acute stroke units available within each country. Most eastern European countries have a well‐developed neurological care system for acute stroke but still have urgent technological and socioeconomical needs. The leading role of clinical neurology in acute stroke care is visible in most but not all European countries.
Pramipexole in the treatment of restless legs syndrome: a follow‐up study
Authors: Montplaisir J. , Denesle R. , Petit D.
Published: March 2003

The restless legs syndrome (RLS) is a condition characterized by unpleasant limb sensations occurring at rest and associated with an irresistible urge to move. Several treatments are used to treat RLS including benzodiazepines, opioids, dopaminergic agents, clonidine and anticonvulsant drugs such as carbamazepine and gabapentine. Dopaminergic agents are now considered the treatment of choice for RLS. Levodopa is effective in treating RLS; however, several patients treated with levodopa at bedtime developed morning or late afternoon restlessness. Recently, more attention has been paid to dopamine receptor agonists. Ergoline derivatives, bromocriptine and pergolide were found effective, but require concomitant administration of domperidone, a peripheral dopamine antagonist. In a recent study, we studied the efficacy and innocuity of pramipexole, a new dopamine agonist with a higher affinity for the D3 receptor subtype of the D2 family, in a double‐blind, placebo‐controlled, randomized trial. Pramipexole had major effects on RLS symptoms without severe side‐effects. The present study aimed to assess the long‐term efficacy of pramipexole. Seven patients were treated with the drug for a mean follow‐up duration of 7.8 months. Treatment was started at a dosage of 0.25 mg, and progressively increased until the optimal therapeutic effect was obtained. Home questionnaires were completed for 7 consecutive days, after one month and after a mean of 7.8 months of treatment with pramipexole, assessing leg restlessness during the daytime, in the evening, at bedtime and during the night. There was no evidence of a decrease in the therapeutic effect of pramipexole in these patients, even 7.8 months after the initiation of treatment. The optimal dosage was 0.25 mg for one patient, 0.5 mg for five patients and 0.75 mg for one patient. While there was a progressive increase in severity of leg restlessness from daytime to nighttime before treatment, a suppression of leg restlessness was observed throughout the 24 h with a single dose of pramipexole at bedtime. The remarkable efficacy of pramipexole raises the possibility that the D3 receptors of the mesolimbic system may be more specifically involved in the physiopathology of RLS.
The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial
Authors: Boyd R. N. , Dobson F. , Parrott J. , Love S. , Oates J. , Larson A. , Burchall G. , Chondros P. , Carlin J. , Nattrass G. , Graham H. K.
Published: March 2003

Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function. We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX‐A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial. Thirty‐nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year + 7 months–4 years +10 months) entered the trial. Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V. After concealed randomization, 20 were allocated to the control group and 19 to the intervention group. Thirty‐five children completed the follow up at 1 year. The novel intervention group received up to 4.0 U BOTOX®/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace. The control group received clinical best practice comprising physiotherapy but no hip abduction bracing. Both groups showed improvements in total Gross Motor Function Measure (GMFM) score [mean 6.0% BTX‐A group; 6.1% Control; 95% CI – 6.7, 6.5 (NS)], however, there was no additional treatment effect for the study group. There were similar improvements on GMFM goal scores and GMFM‐66 scores, but again no additional treatment effect was observed. Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX‐A/SWASH treated group than the control group. In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40%. A longer‐term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement.
Spasticity management in the child with spastic quadriplegia
Authors: Gormley Jr. M. E. , Krach L. E. , Piccini L.
Published: March 2003

In children with spastic quadriplegia, also described as ‘whole body involvement’, spasticity can interfere with motor function, contributes to the development of deformities and adversely impacts on care, positioning, and comfort. In this population, spasticity interventions address goals such as improving comfort, reducing pain, easing the burden of carers, slowing the progression of musculoskeletal deformities and perhaps improving function. Children with severe diplegia are distinguished from those with quadriplegia by their ability to ambulate, as well as by a greater emphasis being placed on functional motor goals even though similar treatment modalities are often employed to manage spasticity. The many treatment options currently available include, but are not limited to, botulinum toxin type A, phenol neurolysis, oral medications, intrathecal baclofen, selective dorsal rhizotomy, and orthopaedic surgery. The integration of these treatment modalities can help to optimize the overall care and function for a child with spastic quadriplegia or severe diplegia. However, the development of a management programme is complex and needs to take into account many factors, including age, weight and nutritional status, rate of progression of musculoskeletal deformities, developmental potential, comorbid conditions, current functional status and prognosis, and family and patient treatment goals. Children with marked spasticity are likely to benefit from a combination of interventions, rather than a single treatment modality. Because of these complexities, management should be planned and coordinated by a multidisciplinary team of medical and allied health professionals which recognizes the central role of the family in all decisions. Once the special characteristics of the child with spastic quadriplegia and the various treatment options are understood, outcomes can be maximized.
Management of upper limb dysfunction in children with cerebral palsy: a systematic review
Authors: Boyd R. N. , Morris M. E. , Graham H. K.
Published: March 2003

Effective use of the upper limb can impact on educational outcomes, participation in activities of daily living and vocational options for many children with cerebral palsy (CP). This article presents the results of a systematic review of the literature on the management of upper limb dysfunction in children with CP. The range of management options includes therapies such as physiotherapy, occupational therapy, neurodevelopmental therapy and conductive education; peripheral splinting and casting; focal or generalized pharmacotherapy; and surgery to improve upper limb function or correct deformity. A literature search identified 60 papers, of which four were randomized controlled trials and 44 were prospective studies with objective outcome measures. Principal studies undertaken for each type of treatment and the efficacy of the different types of treatment were critically evaluated. In addition, the current level of evidence for each study was evaluated according to Sackett’s (1989) model and ICIDH‐2 classification. A close examination of two relatively new treatments for upper limb spasticity, constraint induced movement therapy and botulinum toxin type A (BTX‐A) was conducted with reference to more extensive data on the efficacy of BTX‐A in the lower limb.
T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis. A prospective 18 months follow‐up study
Authors: Sailer M. , Losseff N. A. , Wang L. , Gawne‐Cain M. L. , Thompson A. J. , Miller D. H.
Published: March 2003

We investigated the relationship between local tissue destruction, diffuse cerebral atrophy and clinical progression in patients with established multiple sclerosis (MS). Twenty‐nine patients with MS (13 patients with relapsing–remitting and 16 with secondary progressive disease) were included in a prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, T2 hyperintense lesion volumes at baseline and at 18 months follow‐up, and the volume of monthly enhancing lesions from month 0 to month 9 were assessed on magnetic resonance imaging (MRI) brain scans using highly reproducible semi‐automated quantitative techniques. The main outcome measures were the MRI parameters and disability on Kurtzkes’ Expanded Disability Status Scale.

There was a significant correlation between the change (increase) in T1 lesion volume and progressive cerebral atrophy, whereas no correlation between the T2 lesion volume and atrophy was seen over the same follow‐up period. The change in T1 lesion volume correlated more strongly than did T2 lesion volume change with the change in disability. We conclude that hypointense abnormalities detected in T1‐weighted brain scans and cerebral atrophy may be directly linked. Although one should bear in mind some potential for reversibility due to inflammatory, oedematous lesions, these MR measures are a useful marker of progressive tissue damage and clinical progression in established MS.
A review of the causes of central pontine myelinosis: yet another apoptotic illness?
Authors: Ashrafian H. , Davey P.
Published: March 2003

One of the well recognized stimuli for central pontine myelinosis (CPM) is the rapid correction of chronic hyponatraemia. Conventionally this has been perceived to lead to pontine glial cell swelling through osmosis and eventually to cell death. However, although a purely osmotic argument has been central to any patho‐physiological understanding of CPM, there are deficiencies in this approach that do not account for why certain individuals develop CPM with relatively mild osmotic insults. Here we review the varying aetiologies of CPM and propose a novel hypothesis for CPM causation by suggesting that individuals predisposed to CPM have inadequate energy provision as well as other factors that result in a pro‐apoptotic drive, which renders them susceptible to brain injury from diverse causes. In CPM, the precipitant of brain injury appears to be osmotic stress. Furthermore, this model suggests a number of therapeutic interventions that may prevent or at least mitigate the consequences of CPM.
Ischemic stroke of unusual cause: clinical features, etiology and outcome
Authors: Arboix A. , Bechich S. , Oliveres M. , García‐Eroles L. , Massons J. , Targa C.
Published: March 2003

The clinical features, etiology and neurological outcome of ischemic stroke of unusual cause (ISUC) have rarely been reported. We retrospective reviewed all patients with this stroke subtype entered in the Sagrat Cor Hospital of Barcelona Stroke Registry, which includes data from 2000 consecutive first‐ever stroke patients admitted to the hospital between 1986 and 1995. Patients with previous ischemia and/or hemorrhagic stroke were excluded. Topographic, anamnestic, clinical and neuroimaging characteristics of ISUC were assessed. Predictors of this stroke subtype were determined by logistic regression analysis. Ischemic stroke of unusual etiology was diagnosed in 70 patients (32 men and 38 women), with a mean ± SD age of 52 ± 22.4 years. This stroke subtype accounted for 4.3% of all first‐ever strokes and 6% of all first‐ever brain infarcts. Etiologies included hematological disorders in 17 cases, infection in 11, migraine stroke in 10, cerebral infarction secondary to venous thrombosis in nine, primary inflammatory vascular conditions in six and miscellaneous causes in 17. In the multivariate analysis after excluding cerebral venous thrombosis (n = 9) and arterial dissection (n = 4), because of typical clinical and radiological features, independent predictors of ISUC included 45 years of age or less (odds ratio [OR] 14.8), seizures (OR 6.8), headache (OR 5.2), hemianopia (OR 2.6) and occipital lobe involvement (OR 3.0). Patients with ISUC presented a lower in‐hospital mortality rate (7.1% vs. 14.4%; P < 0.05), were more frequently symptom free at discharge (35.7% vs. 25.8%; P < 0.05) and experienced a longer mean length of hospital stay (23.7 days vs. 18.2 days; P = 0.06) than non‐ISUC patients. We conclude that ISUC is infrequent, etiologies are numerous and hematologic disorders are the most frequent cause. We emphasize the better prognosis and the need to distinguish it from other ischemic stroke subtypes which have a different treatment approach and outcome.
A severe frontal–parietal lobe syndrome following cerebellar damage*
Authors: Botez‐Marquard T. , Bard C. , Léveillé J. , Botez M. I.
Published: March 2003

We report a case study of a frontal and parietal lobe syndrome with memory loss after unilateral left‐sided cerebellar damage caused by a stroke in a patient with right cerebellar unusual developmental agenesis. The syndrome consisted of severe deficits in planning an organized sequence of events, in visuo‐constructive abilities and inappropriate jocularity. These changes are ascribed in part to cerebellar‐pontine lesions with resulting frontal lobe diaschisis as documented by single‐photon emission computed tomography in the absence of morphological damage to the neocortex.
Familial migraine with and without aura: clinical characteristics and co‐occurrence
Authors: Kallela M. , Wessman M. , Havanka H. , Palotie A. , Färkkilä M.
Published: March 2003

Migraine with aura (MwA) and migraine without aura (MwoA) are the two common forms of migraine. Many migraine patients suffer from both kinds of attacks. In a questionnaire‐based study using the current International Headache Society (IHS) criteria we determined the clinical characteristics and occurrence of MwA + MwoA in 1000 migraine patients belonging to 210 Finnish migraine families. Nine hundred and six patients were able to indicate whether they suffered from MwA (but not MwoA), migraine aura without headache (migraine equivalent) (but not MwA) or MwA and MwoA. Of these patients, 3.2% had experienced MwoA, 11.1% MwA, 40.6% MwA + MwoA, 23.5% MwoA and 20.3% MwA‐like symptoms not meeting the IHS criteria. The high prevalence of MwA attacks in the families studied supports the belief that aura has a strong hereditary component. The MwA + MwoA patients had significantly more severe attacks, more typical headache and more prodromal symptoms than the MwA and MwoA subjects. Therefore, it is possible that there is a continuum with pure MwA at the neural and pure MwoA at the headache end of the spectrum, and MwA + MwoA lying in between the two. The MwA + MwoA patients would thus be liable to both types of migraine, making their attacks more characteristic and more severe. This would also explain why the co‐occurrence of MwA and MwoA is more common in the clinic compared with population based epidemiological studies. These findings have consequences for future research on liability genes for migraine.
The perception of memory failures in patients with epilepsy
Authors: Piazzini A. , Canevini M. P. , Maggiori G. , Canger R.
Published: March 2003

The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population.

We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50).

A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests.

Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05).

It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception.
A case with cerebral thrombosis receiving tamoxifen treatment
Authors: Akdal G. , Dönmez B. , Çakmakçı H. , Yener G. Gülmen
Published: March 2003

Cerebral sinus thrombosis (CST) is known to be related to a number of underlying aetiologies including otitis media, trauma, pregnancy, birth control pills, tumours, malnutrition, dehydration, haematologic disorders and malignancy (Fishman, 2000; Raizer and Abbott, 2000). We present the case of a patient with breast cancer receiving the antioestrogen drug tamoxifen who developed CST.

A 40‐year‐old female presented as an emergency with a 10‐day history of headache and left sided weakness. On questioning her past medical history included a diagnosis of breast cancer 3 years ago treated by radical mastectomy and tamoxifen 20 mg daily. At the time of admission, neurologic examination revealed a mild left sided hemiparesis and a present Babinksi sign. Non‐contrast enhanced tomography was normal. Magnetic resonance imaging (MRI) showed thrombosis in the superior sagittal sinus, right lateral sinus and jugular vein in addition venous infarction in the right temporal lobe was present (Figs 1a and b). Routine haematology and biochemistry was normal. Anticoagulation tests, antithrombin III, protein S and C levels were also found to be normal. She was treated with anticoagulation therapy and her hemiparesis improved within 3 days. Control MRI showed the resorption of the venous infarction and resolution of the thrombosis (Fig. 1c).

 T1 weighted contrast enhanced axial (a) and coronal (b) images show unenhancing thrombus in superior sagittal sinus and venous heamorrhagic infarction in the right temporal lobe. Control T1 weighted contrast enhanced MRI image (c) reveals resolution of the thrombus in superior sagittal sinus.

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Neurofibromatosis and glioblastoma in a case of multiple sclerosis
Authors: Pál E. , Gömöri É. , Gáti I.
Published: March 2003

The case of a 37‐year‐old woman is presented. Cutaneous neurofibromatosis was associated with a progressive course of multiple sclerosis. Unexpectedly, autopsy revealed a right hemispheric glioblastoma which was silent during her life.