bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping of genes and ESTs assigned to 17q11.2 to a YAC contig centred on the NF1 gene
Authors: Corrado Lucia , Riva Paola , Venturin Marco , Bentivegna Angela , Gervasini Cristina , Larizza Lidia
Published: March 2003

Background The 17q11.2 cytogenetic band is partially covered by the WC17.3 YAC contig, but the position on this contig of many D‐segments, genes and ESTs assigned to the region is not unambiguous. A major reference gene of the region is NF1, involved in neurofibromatosis type 1 and deleted with flanking genes in a subset of patients with NF1 microdeletion syndrome. Several genes of medical relevance also map to the 17q11.2 band.

Methods We assigned genes, markers and ESTs mapped to the 17q11.2 cytogenetic band to selected YACs and PACs by PCR screening and Southern hybridization of PFGE blots. YAC chimerism was detected by FISH which also allowed the refining of gene/marker order. New STSs were generated by cloning and sequencing Alu–Alu or Alu–vector fragments obtained from YACs.

Results A > 7 Mb contig centred on the NF1 gene and consisting of 26 YACs and 8 PACs has been built up to cover most of the 17q11.2 cytogenetic band. Within the contig, we ordered 11 known and 8 novel STSs, 18 ESTs and 11 known genes, a few of which are involved in genetic diseases. Additional genes loosely assigned to 17q11.2 could be located outside the contig. The contig clones with the wide panel of anchored STSs, genes and ESTs provide a tool for the FISH characterization of gross deletions in NF1 patients with complex phenotypes and any constitutional/somatic chromosomal rearrangement affecting 17q11.2. Crosslinking of the telomeric side of our contig to the centromeric side of the nearby chemokine contig has been established, thus providing a long‐range integrated map for the isolation of disease genes and the construction of a transcription map.
Observation of null alleles of microsatellite markers in a Chinese population
Authors: Wang Zhaoxi , Niu Tianhua , Lunetta K. L. , Xu Xin , Fang Zhian , Xu Xiping
Published: March 2003

Introduction  Genotyping of a set of microsatellite markers is often necessary to map genes for complex human diseases by linkage analysis. Presence of null alleles (such as a mutation in the primer‐binding sequence) can lead to pseudo‐deficiency of heterozygosity.

Materials and methods  We completed a genomic scan using 367 autosomal markers on 1477 Chinese subjects in a total of 337 nuclear families. Two markers with apparent non‐Mendelian inheritance patterns were further investigated: marker GGAA15B08 results were re‐scored, and marker GATA29A01 was re‐genotyped using redesigned primers.

Results  The GGAA15B08 marker was found to contain a relatively frequent (24.4%) 185‐bp allele in the Chinese that was previously treated as a ‘null allele’. Marker GATA29A01 contained a null allele due to a mutation within the annealing region of its reverse primer. With a pair of redesigned PCR primers, the null allele diminished. In this study, we have a power > 82% to detect null alleles of frequency 0.04 or greater.

Discussion  The presence of GATA29A01 null alleles in this population was quite common (31.4%). Identification of markers with null alleles in our study has great implications in paternity testing, linkage analysis and forensic DNA testing. Particular care should be taken in analysing microsatellite genotype results to avoid this problem.
Charles Darwin, ichthyology and the species concept
Authors: Pauly Daniel
Published: March 2003

This contribution presents the ichthyological writings of Charles Darwin (1809–1882), by periods, viz. ‘the years prior to the voyage of the Beagle’ (about 1825–1830); ‘the Beagle years’ (1831–1836); ‘from the return of the Beagle to the Foundation of Origin’ (1837–1844); and ‘the mature Darwin’ (1845–1882). Overall, this material covers 45 000 words penned by Darwin, but represents only 0.7% of his lifetime output of about 6 million words, indicating a limited interest in fish. However, this sample, briefly described here, but analysed in great detail in a forthcoming volume on Darwin's Fishes, allows drawing inferences on Darwin's working style that were missed in conventional biographies. On the other hand, it is suggested, based on a close reading of the 6th (1876) edition of Origin, that Darwin was not particularly interested in the theoretical issues now associated with the species concept, nor indeed with other levels of the Linnean system.
Changes in functional outcome in inpatient stroke rehabilitation resulting from new health policy regulations in Italy
Authors: Paolucci S. , Traballesi M. , Gialloreti L.E. , Pratesi L. , Lubich S. , Antonucci G. , Caltagirone C.
Published: March 2003

This study was designed to assess whether enforcement of new health policy regulations in Italy limiting fully paid hospital stay to 60 days has actually caused a decrease in rehabilitation outcomes of stroke patients. Final sample included 370 out of 398 consecutive patients hospitalized between 1993 and 1996 for first stroke sequelae. Rehabilitation results were compared between subgroups of patients admitted before and after new Italian regulations. Length of stay was significantly (p < 0.001) shorter in 1996 than in previous years. However, between 1993 and 1996 a significant (p < 0.05) decrease in effectiveness on mobility and a significant (p < 0.05) increase in “low responders” on both daily living activities and mobility was observed. Moreover, in 1995–96 the precocious discharge of patients compromised stabilization of recovery with subsequent functional worsening. After discharge, outpatient rehabilitation treatment was able to conserve achieved mobility status, but not functional status on daily living activities. We suggest revising the present regulation for medical rehabilitation services to one based on FRGs (functional related groups), so that the appropriate treatment can be carried out for each patient.
The striatum in a putative cerebral network activated by verbal awareness in normals and in ADHD children
Authors: Lou H.C. , Andresen J. , Steinberg B. , McLaughlin T. , Friberg L.
Published: March 2003

The aim of the present study was to evaluate the striatum's involvement in verbal awareness (semantic processing and supra‐modal attention) in normals and children with attention deficit hyperactivity disorder (ADHD). Our previous finding of striatal hypoperfusion in ADHD at rest, supports our prediction that the striatum will also show reduced activation in response to tasks requiring verbal awareness.

Regional cerebral blood flow (rCBF) was studied with the Xenon133 SPECT method in 12 boys with ADHD and six normal controls. The experimental controls included: (1) White Noise, (2) Passive Listening to a series of animal names, and (3) Detection of Targets (“dangerous animals”) from the same series of animal names. The conditions were selected to isolate the semantic processing (Passive Listening – White Noise) and supra‐modal attention components (Detection of Targets – Passive Listening of verbal awareness).

ADHD children had decreased rCBF in the right striatum when compared to normals (mean difference from grand mean of each subject 8.06 ml/100 g/min vs 14.16 ml/100 g/min, p < 0.05).

Factor analysis of the rCBF data revealed high factor I loadings for the frontal and striatal regions, which, in conjunction with the nature of the experimental conditions supported the inference that factor I mediated verbal awareness. Factor scores, which summarized the activity of all of the regions of interest (ROI's) on factor I, were differentially affected by the language component of the experimental tasks. Function scores were derived from factor I for the anterior cingulum and infero‐frontal regions to evaluate their respective involvement in supra‐modal attention and semantic processing. Function scores were also developed for the striatum, because of its central location and potential role in ADHD. The anterior cingulum was activated by supra‐modal attention. The infero‐frontal and the striatal regions were both activated by the language demands of the tasks. However, the striatum demonstrated reduced function scores (p < 0.05) in ADHD for all tasks.

Our finding that the anterior gyrus cinguli were activated by supramodal attention and that the infero‐frontal and striatal regions were activated by semantic processing supports the involvement of these ROI's in verbal awareness. Furthermore, the depressed functional contribution of the striatum to verbal awareness in ADHD children is consistent with and helps to explain their reduced cognitive control over behaviour and mental function.
Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta‐1a after intramuscular and subcutaneous administration
Authors: Munafo A. , Trinchard‐Lugan I. , Nguyen T.X.Q. , Buraglio M.
Published: March 2003

The pharmacokinetics and pharmacodynamics of recombinant human interferon beta (IFN‐β‐la) were compared after intramuscular administration of two preparations (Rebif® and Avonex™) and subcutaneous administration of Rebif®. Healthy volunteers (n= 30) received a single dose (6O μg) of each of the three treatments in a randomised crossover study. Serum concentrations of IFN‐β were measured by enzyme‐linked immunosorbent assay over 24 h after dosing. Pharmacodynamics were assessed by measurement of intracellular 2′,5′‐oligoadenylate synthetase activity, and serum neopterin and β2‐microglobulin concentrations, over 144 h after dosing. There was no significant difference between the three treatments in peak serum IFN‐β concentrations (Cmax) or area under the concentration‐time curve (AUC). No significant differences in pharmacodynamic measures were observed between the three treatments. It is concluded that the bioavailability of IFN‐β‐1a is equivalent after subcutaneous or intramuscular administration of Rebif®, and intramuscular administration of Avonex™.
Thymectomy: its role in the management of myasthenia gravis
Authors: O'Riordan J.I. , Miller D.H. , Mottershead J.P. , Pattison C. , Hirsch N.P. , Howard R.S.
Published: March 2003

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) for thymectomy over a 66 month period were reviewed. There were 53 patients, 20 male and 33 female, mean age 35.2 years (18–74) and median ITU stay of 5 days (2–30). Indications for thymectomy were thymic enlargement on computed tomography (34%), persistence of generalized symptoms (38%), a combination of both (20%), steroid side effects or dependency (4%) and progressive bulbar symptoms (4%). Following thymectomy, thymic histology revealed thymic follicular hyperplasia (26/53; 49%), atrophy (11/53; 21%), thymoma (12/53; 23%) and normal thymus (4/53; 8%). Post‐operatively 23% required prolonged intubation (> 48 hrs); two patients required a tracheostomy 10 and 13 days post‐operatively. Plasma exchange was required for two patients (3.8%) due to persistent severe myasthenic weakness. Three patients (6%) developed a post‐operative chest infection and one pseudomembranous colitis. There were no post‐operative mortalities during the study period. After 2 years, 35% of patients were in remission and 46% had ocular or mild generalized symptoms only. Thymectomy for myasthenia gravis is followed by sustained clinical improvement in the majority of patients. The appropriate post‐operative management of these patients is best undertaken in a specialized neuro‐intensive care setting.
Worsening in seizure frequency and severity in relation to folic acid administration
Authors: Guidolin L. , Vignoli A. , Canger R.
Published: March 2003

We report a case of increase in seizure frequency and severity in a 26‐year‐old woman receiving folic acid at a dosage of 0.8 mg/day. She had symptomatic partial epilepsy with simple and complex seizures treated with carbamazepine. She was planning pregnancy and we prescribed folic acid for prevention of neural‐tube defects. In the next few days she had a generalized tonic–clonic seizure for the first time and a significant increase in seizure frequency. Because of the temporal relation between the seizure worsening and the administration of folk acid, we hypothesize a role of folic acid in provoking seizures, as has been reported in the literature.
A novel mutation Asp90Val in the SOD1 gene associated with Japanese familial ALS
Authors: Morita Mitsuya , Abe Koji , Takahashi Mitsu , Onodera Yoshiaki , Okumura Hitoshi , Niino Masaaki , Tashiro Kunio , Nakano Imaharu , Itoyama Yasuto
Published: March 2003

We have identified a novel mutation in exon 4 of the Cu/Zn superoxide dismutase (superoxide dismutase 1: SOD1) gene (GAC to GTC), which resulted in an Asp90 to Val substitution in a Japanese family with amyotrophic lateral sclerosis (ALS) inherited as an autosomal dominant trait. The patients in this family usually died in 2–3 years without sensory or urinary impairment. The SOD1 activity was lower in the proband as compared to the normal controls. The clinical characteristics of this family resemble those of some patients heterozygous for the Asp90Ala mutation, but both the clinical features and SOD1 activity of this family differ from those of patients homozygous for the ASP90Ala mutation.
Post‐partum cerebral angiopathy. A rare cerebrovascular complication
Authors: Al‐Sous Walid , Bohlega Saeed , Al‐Kawi Zuheir , McLean Donald , Shukri Khalid
Published: March 2003

We describe two patients with post‐partum cerebral angiopathy. (Case 1) A 24‐year‐old patient developed vaginal bleeding 1 day post‐partum. She received blood transfusion and ergometrine. Four days later she experienced severe occipital headache, loss of vision and generalized seizures. An MRI showed right occipital lesion. She was treated with phenytoin and prednisone. Her vision returned to normal within 2 days. Cerebral angiography showed multiple segmental narrowing; 6 h later severe occipital headache and cortical blindness recurred. She was treated with nimodipine and prednisone with complete recovery in 10 days. (Case 2) On the 7th post‐partum day a 24‐year‐old patient was given ergometrine. One day later she developed severe headache and hypertension, followed by drowsiness, right hemiplegia and aphasia. A left frontal hematoma was seen on the CT scan. Cerebral angiography showed multiple segemental narrowing. Resolution of this angiography was confirmed on follow‐up angiography. Post‐partum cerebral angiopathy is a rare complication of a normal pregnancy. It may present as an ischemic or hemorrhagic stroke. The transience of this severe complication and its association with the administration of drugs with strong vasoconstrictive properties suggest and etiological relationship. Other factors and the exact mechanism are unclear.
Pituitary apoplexy: a transient benign presentation mimicking mild subarachnoid hemorrhage with negative angiography
Authors: Hernández Amalia , Real M. Angeles Del , Aguirre Miguel , Vaamonde Julia , Gudín María , Ibáñez Ramón
Published: March 2003

We report on a patient who presented with isolated transient headache as the only manifestation of pituitary apoplexy. A high index of suspicion and MRI led to the diagnosis.
The burden of migraine to the individual suffer: a review
Authors: Dahlöf Carl G.H. , Solomon Glen D.
Published: March 2003

This review of the literature reveals that migraine is a common, chronic condition featuring episodic attacks which vary in severity and sympatomatology. Throbbing, unilateral headache, which is aggravated by activity, is the most prominent feature, although a high proportion of sufferers also experience phonophobia, photophobia, and nausea, which may lead to vomiting. Preceding aura is a less common feature of the attack. The frequency and duration of migraine attacks varies widely between individuals, though the median frequency is around 1 attack per month and median duration is roughly 24 h. Migraine attacks can have a profound effect on the day‐to‐day lives and well‐being of the sufferer. In the long term, migraine may cause profound emotional changes and result in coping strategies that interfere with working, social and family life and many normal daily activities. These effects are apparent in quality of life studies on migraine patients. Thus, the impact of migraine on many quality of life parameters is similar to that of other chronic conditions such as osteoarthritis, diabetes and depression. Reduction in the personal burden of migraine can be facilitated by encouraging migraine sufferers to consult their doctor, through accurate diagnosis of migraine headaches and assessment of the disability suffered by the migraineurs, and through improved and well‐executed treatment strategies.
Effect of NG‐nitro‐L‐arginine methyl ester a nitric oxide synthase inhibitor on neurotransmitter receptor systems in aged rats
Authors: Araki Tsutomu , Oshima Yoshiteru , Kato Hiroyki , Shuto Katsuro , Itoyama Yasuto
Published: March 2003

In order to examine the effect of age and nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methl ester (l‐NAME) we studied the changes on major neurotransmitter receptor systems in 6 (adult and 24‐month‐old (aged) Fischer male rats using receptor autoradiography. l‐name was administrated intraperitoneally in aged rats once a day for 4 weeks. [3H]QNB (quinuclidinyl benzilate) 3HC (hemicholinium‐3) [3H] muscimol 3H] SCH 23390 ([N‐methyl‐3H] N‐methyl‐3H]R[+]‐8‐chloro‐2 3 4 5‐tetrahydro‐3‐methyl‐5‐phenyl‐7‐il‐benzazepine) 3H] mazindol were used as markers of muscarinic acetylcholine receptors high‐high‐affinity choline uptake sites GABAA (γ‐aminobutyric acid (SP2)A) receptors dopamine D1 receptors dopamine D2 receptors and dopamine uptake sites respectively. The age‐related change in 3H muscimol binding in the brain was more pronounced than that in [3H] QNB 3H]HC 3H]SCH 23390 3H] nemonapride and 3H] nemonapride and 3H] mazindol binding.Chronic treatment (4 weeks) with l‐NAME caused no significant changes in [sp1)3H] muscimol 3H SCH 23390 and [3H] nemonapride binding in most areas of aged rat brain as compared with vehicle‐treated aged animals. However chronic treatment with l‐NAME caused a significant reduction in 3H] HC and 3H] mazindol binding in any brain regions of aged rats in comparison with the vehicle‐treated aged animals. These results demonstrate that the GABAergic system is more susceptible to aging processes than cholinergic and dopaminergic systems in teh brain. Furthermore our findings suggest that nitric oxide may play some role in the regulation of choline uptake and dopamine uptake systems during aging processes.
Current status of multiple sclerosis therapy in Germany: a national survey
Authors: Heesen Christoph , Hauer Sabine , Hadji‐Abdolrahim Bijan , Berenbeck Christine , Buhmann Carsten , Emskotter Thomas , Neurology Department of
Published: March 2003

We conducted a semi‐standardized enquiry concerning diagnostic, immunotherapeutic and supportive care strategies for multiple sclerosis (MS). A questionnaire was sent to all German neurological departments in December 1996, with 63% (n = 244) responding before May 1997. As might be expected, MS therapy in Germany is not very standardized. Most clinics use intravenous steroids for treating relapses, although with different dosing regimens. Nevertheless, oral steroids are also used. Interferon‐β and azathioprine are both used for the treatment of relapsing‐remitting MS at the same frequency. Only 33% of German neurological departments said that they used an immunomodulating agent for chronicprogressive cases, indicating it in about 50% of cases. Azathioprine is the drug of first choice, followed by methotrexate. Regarding supportive care measures, the technique of intermittent self‐catheterization is widely under‐represented. Despite the lack of conclusive evidence from prospective studies for the value of azathioprine, it is still one of the most commonly used drugs for the treatment of relapsing‐remitting and chronic‐progressive MS. There was no evidence of a consensus on treatment standards for chronic‐progressive disease courses.
Febrile convulsions in a Serbian region: a 10‐year epidemiological study
Authors: Pavlovic Milen V. , Jarebinski Mirjana S. , Pekmezovic Tatjana D. , Marjanovic Borivoje D. , Levic Zvonimir M.
Published: March 2003

The first population‐based study in the central region of the Republic of Serbia (total population 283,103) was carried out to assess some epidemiological features of febrile convulsions among children of between 6 months and 5 years of age. During the 10‐year period, 1986 to 1995, there were 570 cases of the first febrile convulsions (287 males and 283 females). The average annual incidence rate was 3/1000 (2.9/1000 in males and 3.0/1000 in females), with the highest in 1995. During the study period, a significantly increased linear regression trend was observed. During the follow‐up period of 5 years for children who had their first febrile convulsions in 1989 and 1990 (total 154 cases), 27 (17.5%) had a recurrence of the disorder, and ten (6.5%) had one or more afebrile seizures, of whom seven children (4.5% of total sample) developed epilepsy (recurrent afebrile seizures).
Circadian rhythm sleep disorder associated with pontine lesion
Authors: Kashihara Kenichi , Takahashi Koji , Shohmori Toshikiyo
Published: March 2003

A 55‐year‐old man presented with excessive daytime sleepiness and a circadian rhythm sleep disorder. Magnetic resonance imaging of the brain revealed a pontine lesion distinguishable from major cerebrovascular disease, demyelination and neoplasm. Benzodiazepines, antidepressants, methylcobalamine and thyroxine failed to synchronize the circadian rhythm. Antiepileptic drugs aggravated the condition, while melatonin and protireline partially relieved the patient from poorly controlled sleep disorder. A pontine lesion appeared to be related to the circadian rhythm sleep disorder of the patient.
Transient amnesia triggered by acute marijuana intoxication
Authors: Stracciari Andrea , Guarino Maria , Crespi Cristina , Pazzaglia Paolo
Published: March 2003

We report an unusual case of sudden isolated transient amnesia triggered by acute marijuana use. The memory disorder, apart from the long duration, had the characteristics of a transient global amnesia‐like episode. Acute marijuna intoxication can affect memory more globally and severely than previously reported.
Colour vision abnormalities and movement time in Parkinson's disease
Authors: Müller Thomas , Kuhn Wilfried , Büttner Thomas , Przuntek Horst
Published: March 2003

Visual system dysfunction has been reported in Parkinson's disease (PD). The objective of the present study was to evaluate a putative association of distorted colour vision and delayed initiation and execution of movement in PD. We performed the Farnsworth‐Munsell 100‐hue test and estimated the total error score in 30 previously untreated parkinsonian patients and 30 age‐ and sex‐matched controls. We then determined slowness in motor readiness and motor programming in the parkinsonian subjects on the same day. Subjects were asked to press a start button and release it after the randomized appearance of a visual stimulus and to move their right index finger to a reaction button as quickly as possible. Reaction time was considered as elapsed time between onset of the stimulus light and release of the start button, movement time was the time period between release of the start button and the pressing of the reaction button. Significant differnces appeared between parkinsonian patients' and controls' reaction times (P= 0.007), movement time (P= 0.001) and total error score (P= 2.23E‐08). A significant relation (Spearman R= 0.473, P= 0.008) was found between movement time and total error score, but not between reaction time and total error score (Spearman R= 0.259, P= 0.166). We conclude, that visual dysfunction and execution of movement are more influenced by altered dopaminergic neurotransmission in PD in comparison to the initiation of movement.
Bilateral thalamic pain secondary to bilateral thalamic infarcts relieved by a further unilateral ischaemic episode
Authors: Cordery Rebecca J. , Rossor Martin N.
Published: March 2003

This study reports a patient with severe, debilitating bilateral thalamic pain caused by bilateral thalamic infarcts. The authors consider it to be a unique case as a further clinically unilateral lesion led to pain relief bilaterally.
Cerebral embolism in a patient with polycythemia rubra vera
Authors: Segura T. , Serena J. , Teruel J. , Dávalos A.
Published: March 2003

Polycythemia rubra vera (PRV) is a rare haematological disorder that has a high risk of stroke, although the pathophysiological origin of the cerebral ischaemia in this disease is not well known.

We report a case of a stroke patient with PRV in whom bilateral embolic signals were detected by transcranial Doppler (TCD). Cerebral computed tomography showed a cortical middle cerebral artery infarction, echocardiography was normal, duplex‐scan showed moderate left carotid stenosis and digital angiography disclosed right siphon stenosis. TCD examinations in the acute phase repeatedly showed a great number of bilateral microembolic signals (MESs). Four months later magnetic resonance angiography showed no flow signal in the right siphon and a severe stenosis of the proximal right MCA.

The detection of bilateral MESs in the absence of cardiac sources of embolism observed in this patient suggests that ischaemic cerebral events in PRV may have an embolic origin favoured by a prothrombotic state.
A population‐based study of the associations of stroke occurrence with weather parameters in Siberia, Russia (1982–92)
Authors: Feigin V. L. , Nikitin YU. P. , Bots M. L. , Vinogradova T. E. , Grobbee D. E.
Published: March 2003

Previous studies have established a seasonal variation in stroke occurrence, but none have assessed the influence of inclement weather conditions on stroke incidence in a general population of Russia. We performed a stroke population‐based study in the Oktiabrsky District of Novosibirsk, Siberia, Russia. Included in the analysis were 1929 patients with their first occurrence of ischemic stroke (IS), 215 patients with their first occurrence of intracerebral hemorrhage (ICH) and 64 patients with their first occurrence of subarachnoid hemorrhage (SAH): all patients were aged between 25 and 74 years. The cumulative daily occurrence of total strokes and stroke subtypes was evaluated in relation to aggregated daily mean values of ambient temperature, relative humidity and air pressure by means of Poisson regression analysis to estimate the rate ratio (RR) with corresponding confidence interval (CI) and to identify the weather parameters of most importance. In a multivariate analysis, with adjustment for the effects of season, solar and geomagnetic activity, and age of the patients, low ambient temperature (RR 1.32; 95% CI 1.05–1.66) and mean value of air pressure (RR 0.986; 95% CI 0.972–0.999) were important predictors of IS occurrence, while mild ambient temperature (RR 1.52; 95% CI 1.04–2.22) was an important predictor of ICH occurrence. No relationship between SAH occurrence and any one of the weather parameters studied was revealed. There was no interaction between any meteorological variables that was statistically significant. Inclement weather conditions are associated with the occurrence of IS and ICH in Siberia, Russia. Among the meteorological parameters studied, low ambient temperature and mean air pressure are the most important predictors of IS occurrence, whereas the occurrence of ICH is associated with mild ambient temperature. There is no association between any one of the weather parameters studied and the occurrence of SAH.
Isolated familial hypomagnesaemia with novel neurological features: causal link or chance concurrence?
Authors: Larner A. J. , Williamson C. , Ward N. S. , Acheson J. F. , Robinson S. , Farmer S. F.
Published: March 2003

We report a patient with isolated familial hypomagnesaemia with hypocalciuria, a rare congenital disorder of magnesium metabolism. During adolescence the patient developed neurological and ophthalmological features not hitherto reported in this condition, including seizures, myoclonus, and retinal pigmentary degeneration. These suggested the phenotype of mitochondrial disease, which has been occasionally reported in association with hypomagnesaemia, but subsequent investigations of mitochondrial function were normal. The pathogenesis of this unusual neurological and ophthalmological syndrome therefore remains uncertain.
Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions
Authors: Dac˘ković J. , Rakoc˘ević‐Stojanović V. , Pavlović S. , Zamurović N. , Dragašević N. , Romac S. , Apostolski S.
Published: March 2003

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5‐Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein‐22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51‐year‐old patient with a l.5‐Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure.
Clinical application of transcranial colour‐coded duplex sonography – a review
Authors: Zipper Stephan G. , Stolz Erwin
Published: March 2003

Transcranial colour‐coded duplex sonography (TCCS) is a new and non‐invasive ultrasound application that combines both imaging of intracranial vessels and parenchymal structures at a high spatial resolution.

This manuscript reviews the clinical applications of TCCS with focus on its diagnostic abilities in acute stroke patients. Furthermore, new experimental imaging techniques are discussed.
A putative polymorphic Val44Ala variation in the synphilin‐1 gene is undetectable in Japanese sporadic Parkinson’s disease patients
Authors: Satoh J.‐I. , Kuroda Y.
Published: March 2003

Recently, a novel protein‐interaction partner of α‐synuclein, designated synphilin‐1, is identified as a constituent of Lewy bodies (LB) in Parkinson’s disease (PD) brains. To investigate an involvement of genetic variations of synphilin‐1 in development of sporadic PD, a possible single nucleotide polymorphism (SNP) of T131C corresponding to a valine (Val) to alanine (Ala) substitution at codon 44 in exon 3 of the synphilin‐1 gene was studied in a Japanese population of 55 patients with sporadic PD and 61 patients with non‐PD by direct sequencing analysis. All 116 subjects showed a homozygosity of Val at codon 44 in the synphilin‐1 gene, suggesting that this SNP is unlikely to affect genetic susceptibility to sporadic PD in the Japanese population.
Maurice Ravel and right‐hemisphere musical creativity: influence of disease on his last musical works?
Authors: Amaducci L. , Grassi E. , Boller F.
Published: March 2003

The problem of finding correspondence between a particular neuronal organization and a specific function of the human brain remains a central question of neuroscience. It is sometimes thought that language and music are two sides of the same intellectual coin, but research on brain‐damaged patients has shown that the loss of verbal functions (aphasia) is not necessarily accompanied by a loss of musical abilities (amusia). Amusia without aphasia has also been described. This double dissociation indicates functional autonomy in these mental processes. Yet verbal and musical impairments often occur together. The global picture that emerges from studies of music and its neural substrate is by no means clear and much depends on which subjects and which aspect of musical abilities are investigated.

An illustration of these concepts is provided by the case of the French composer Maurice Ravel, who suffered from a progressive cerebral disease of uncertain aetiology, with prominent involvement of the left hemisphere. As a result, Ravel experienced aphasia and apraxia and became unable to compose. The available facts favour a clinical diagnosis of primary progressive aphasia (PPA), with the possibility of an overlap with corticobasal degeneration (CBD).

In view of Ravel’s clinical history, we propose that two of his final compositions, the Bolero and the Concerto for the Left Hand, include certain patterns characteristic of right‐hemisphere musical abilities and may show the influence of disease on the creative process.
Radiological and manometric diagnosis of cricopharyngeal dysphagia in a Japanese encephalitis survivor
Authors: Chuang Y.‐M. , Kwan S.‐Y. , Lirng J.‐F. , Tiu C.‐M. , Pan P.‐J.
Published: March 2003

Japanese encephalitis (JE) is endemic throughout most of the western Pacific region where Taiwan is located. About half the survivors are left with neurological damages. We report a 55‐year‐old male who survived from JE and was left with sequela of parkinsonism and severe swallowing disorder. Later, it was proved to be cricopharyngeal dysphagia (CPD) using esophagogram and manometry, which disclosed involuntary hypertonic and hyperreflexic cricopharyngeal muscle contraction. CPD, a life‐threatening neurological sequel of JE, has never been reported in the JE survivors before and possibly results from disseminated lesions over pyramidal and extrapyramidal systems.
Relation between homocysteine and non‐fatal stroke in peripheral arterial disease
Authors: Haltmayer M. , Mueller T. , Lange W. , Luft C. , Hainzl A. , Poelz W. , Haidinger D.
Published: March 2003

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non‐fatal stroke in PAD. Evidence of non‐fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high‐performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 μmol/l) than in PAD patients without stroke (15.1 μmol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 μmol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis ≥50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non‐fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.
Depressive symptoms and MRI changes in multiple sclerosis
Authors: Zorzon M. , Zivadinov R. , Nasuelli D. , Ukmar M. , Bratina A. , Tommasi M. A. , Mucelli R. P. , Brnabic‐Razmilic O. , Grop A. , Bonfigli L. , Cazzato G.
Published: March 2003

To determine whether changes in specific regions of the brain can contribute to the development of depression in patients with multiple sclerosis (MS). We prospectively studied 90 patients with clinically definite MS. Disability, independence, cognitive performances, and depressive and anxiety symptoms have been assessed at baseline and 2 years later. At these two time‐points, patients underwent a 1.5‐T magnetic resonance examination of the brain including T1‐ and T2‐weighted images. Calculation of regional and total lesion loads (LL) have been performed by a semiautomatic technique; total and regional brain volumes have been calculated by a fully automatic highly reproducible computerized interactive program. Measurements of LL did not show any significant difference between depressed and non‐depressed patients. Brain atrophy was significantly more conspicuous in the left frontal lobe (P=0.039), in both frontal lobes (P=0.046) and showed a trend towards a difference in the right frontal lobe (P=0.056), in the right temporal lobe (P=0.057) and in both temporal lobes (P=0.072) of depressed patients. Disability, independence and cognitive performances were similar in depressed and non‐depressed patients (P=NS). Spearman correlation analysis and multiple‐regression analysis demonstrated that the severity of the depressive symptoms score was associated both with the disability score and the right temporal brain volume. Destructive lesions in the right temporal lobe can contribute to the severity of depression in patients with MS but the influence of the severity of neurological impairment should be taken into account.
Subarachnoid haemorrhage occurrence exhibits a temporal pattern – evidence from meta‐analysis
Authors: Feigin V. L. , Anderson C. S. , Rodgers A. , Bennett D. A.
Published: March 2003

The aim of the present meta‐analysis was to determine a temporal pattern of occurrence of subarachnoid haemorrhage (SAH). A MEDLINE 1966–2001 and EMBASE (1980–2001) literature search and hand search of relevant references were performed for population‐based incidence studies that reported the time of SAH occurrence. Data from all identified relevant studies were combined into a pooled rate ratio (RR), with corresponding 95% confidence intervals (CI) using the Mantel–Haenszel method. Overall, eight population‐based studies were included in the analysis. A total of 2533 first‐ever cases of SAH were reported in the studies identified. Risk of SAH occurrence was the highest in the period between 6 am and 12 am (RR = 3.19; 95% CI 3.03–3.36; early morning as a reference variable) and between 12 p.m. and 6 p.m. (RR = 2.63; 95% CI 2.47–2.80), in winter and spring (RR = 1.10; 95% CI: 1.02–1.17; and RR = 1.07; 95% CI: 1.01–1.13, respectively; summer as a reference variable) and on Sunday (RR = 1.22; 95% CI 1.09–1.37; Monday as a reference variable). The evidence suggests that occurrence of SAH exhibits a seasonal (winter and spring) peak, diurnal (late morning peak) and daily (Sunday peak) pattern. It is suggested that the occurrence of some major acute vascular events (total ischaemic strokes, intracerebral haemorrhage and myocardial infarction) may be influenced by common triggering factors.
Cerebral vasomotor reactivity of the posterior circulation in patients with carotid occlusive disease
Authors: Gur A. Y. , Bornstein N. M.
Published: March 2003

We evaluated the hemodynamic features of the posterior circulation in patients with severe carotid stenosis by assessing and comparing cerebral vasomotor reactivity (VMR) in the middle cerebral (MCA) and vertebral arteries (VA) by transcranial Doppler and the Diamox (1 g acetazolamide i.v) test. Sixty symptomatic and 111 asymptomatic patients with unilateral severe (>70%) internal carotid artery stenosis were studied. The VMR was 19.2 ± 18.9% for the MCA ipsilateral to the stenosis and 27.3 ± 17.4% on the contralateral side (P < 0.0001) for all patients. It was 18.2 ± 23.2% for the VA ipsilateral to the stenosis and 19.7 ± 21% on the contralateral side (P = NS). The symptomatic patients' VMR of the MCA on the side of stenosis and the opposite side were 19.2 ± 17.6 and 29 ± 17.2%, respectively (P < 0.03). The VMR of the VA remained similar (15.1 ± 21 and 21.6 ± 6%, respectively, P = NS). The asymptomatic patients' VMR of the MCA on the side of the stenosis was also lower (19.2 ± 19.7 vs. 26.5 ± 17.5% on the opposite side, P < 0.001). In contrast, the VMR in the VA was similar (19.8 ± 21.4 and 18.7 ± 19.5%, respectively, P < 0.6, NS). Thus, the VMR of the posterior circulation remained similar regardless of carotid stenosis and a symptomatic/asymptomatic course of carotid occlusive disease, suggesting an independent cerebral vascular reserve capacity of the posterior circulation.
Progressive visual loss due to a muslinoma – report of a case and review of the literature
Authors: Berger C. , Hartmann M. , Wildemann B.
Published: March 2003

Intracranial internal carotid artery (ICA) aneurysms are frequently treated either by microsurgical clipping of the aneurysm neck, by endovascular coiling of the aneurysm sac or by balloon occlusion of the parent vessel. For some broad‐based aneurysms that may not be suitable for any of these options, microsurgical wrapping of the aneurysm wall with muslin or gauze rarely is applied. We report the case of a patient who suffered from a minor stroke because of arterio‐arterial embolism from an intracranial ICA aneurysm. The aneurysm was treated by wrapping muslin material. After 12 months, he experienced progressive visual loss. Cranial magnetic resonance testing magnetic resonance tomography (MRT) revealed a granulomatous inflammation surrounding the site of the aneurysm and affecting optochiasmatic structures. A muslin‐induced optic neuropathy is a rare but serious complication of a chronic inflammatory reaction in response to muslin or gauze used in intracranial aneurysm wrapping. If the foreign body inflammatory reaction to muslin or gauze leads to a mass formation, the term muslinoma or gauzoma is applied. Various treatment strategies include surgery, steroids and cyclophosphamide, but recovery of the vision is not predictable. As a consequence, muslin or cotton gauze should only be applied with great caution in neurovascular surgery.
Do dopamine agonists or levodopa modify Parkinson's disease progression?
Authors: Marek K. , Jennings D. , Seibyl J.
Published: March 2003

During the past decade,in vivoimaging of the nigrostriatal dopaminergic system has been developed as a research tool to monitor progressive dopaminergic neuron loss in Parkinson's disease (PD) and to assess the effect of medication on imaging outcomes. Recently two similar studies compared the effect of initial treatment with a dopamine agonist (pramipexole (CALM‐PD CIT) or ropinirole (REAL‐PET)) or levodopa on the progression of PD as measured by [123I]β‐CIT or [18F]Dopa imaging. These two clinical imaging studies targeting dopamine function with different imaging ligands and technology both demonstrate slowing in the rate of loss of [123I]β‐CIT or [18F]Dopa uptake in early PD patients treated with dopamine agonists compared with levodopa. The relative reduction in the per cent loss from baseline of [123I]β‐CIT uptake in the pramipexole versus the levodopa group was 47% at 22 months, 44% at 34 months and 37% at 46 months after initiating treatment. The relative reduction of18F‐dopa uptake in the ropinirole group versus the levodopa group was 35% at 24 months. These results should be very cautiously interpreted with regard to the effect of dopamine agonists or levodopa on clinical disease progression. These data highlight the need to compare imaging outcomes of dopamine neuronal loss with multiple meaningful clinical endpoints of disease progression in placebo controlled, larger and long‐term studies.
The therapeutic challenges in the older Parkinson's disease patient
Authors: Playfer J. R.
Published: March 2003

The information explosion in Parkinson's disease challenges the individual clinician to apply available knowledge to the management of individual patients. The application of current algorithms and guidelines is not straightforward in the older patient. Decision analysis reveals that clinical decisions may be simple, complex or chaotic. The more factors that have to be taken into account in making a decision, the more that decision moves from being evidence‐based to intuitive. Decisions are made within conceptual frameworks. The dominant models in Parkinson's disease are biomedical or rehabilitation‐based. Although the rehabilitation model lacks a sound evidence base, it is the principles of rehabilitation that dominate the management of the older patient. Analysis of the decisions made in a Parkinson's disease clinic demonstrates that the doctor's role is complex and many decisions taken are not evidence‐based. Parkinson's disease is not a simple movement disorder but a neuro‐psychiatric complex. The incurable nature and chronicity of the disease dictate the need for multidisciplinary working. Quality of life studies reveal wide variations in the expectations and needs of patients. Studies of the impact and costs of the disease put the cost of drugs into perspective. Studies in Parkinson's disease can involve very different populations. A cohort of elderly patients shows significant differences from the populations who are selected to participate in multi‐centre trials. There is an increasing challenge for geriatricians to ensure that pragmatic trials are undertaken. Psychiatric problems – dementia, depression, and hallucinations – are common in the elderly and best management of these problems is unclear. Choices in drug regimes need to take into account the complex interactions between ageing, comorbility and Parkinson's disease.
Changing days
Authors: Whittaker Andrea , McIntosh Barbara
Published: March 2003

The People First conference, which was held in Edinburgh, UK, in 1997, passed the following motion: ‘Day centres should not waste people’s time or people's lives'. This is a challenging statement which will be echoed by many people involved in providing and supporting day services for people with learning difficulties. The present article outlines how the King's Fund Changing Days project has tried to respond to this challenge over the past 5 years. More detailed accounts can be found in the publications which have resulted from the work.
Parallel stigma? Nurses and people with learning disabilities
Authors: Mitchell Duncan
Published: March 2003

The present paper discusses the history of learning disability nursing in the context of its development within the nursing profession and its relationship with people with learning disabilities. The study provides a brief sketch of the development of learning disability nursing as a discrete branch of the nursing profession before exploring its history in the light of theories of marginalization and stigma. Although the present author recognizes the profound differences between the history of people with learning disabilities and those paid to care for them, he seeks to establish some common ground on the basis of parallel stigma.
Presentation, assessment and treatment of depression in a young woman with learning disability and autism
Authors: Long Karen , Wood Harry , Holmes Nan
Published: March 2003

The association between autism and affective disorders in adults with learning disability (LD) is reviewed, alongside a discussion of some of the problems identified with the accurate differential diagnosis of depression in individuals with more severe impairment. This case study describes the presentation, differential diagnosis and treatment of a young woman with a severe LD, autism and depression. Behavioural factors which were felt to reflect this individual's depressive disorder, but which are not usually associated with the diagnosis of depression, are highlighted. Further work on the development and refinement of a reliable method of assessing depression in individuals with LD and autism is discussed.