bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal dominant rolandic epilepsy and speech dyspraxia: A new syndrome with anticipation
Authors: Scheffer Ingrid E. , Jones Loretta , Pozzebon Marchgaret , Anne Howell R. , Saling Michael M. , Berkovic Samuel F. 
Published: January 2005

AbstractWe describe a family of 9 affected individuals in three generations with nocturnal oro‐facio‐brachial partial seizures, secondarily generalized partial seizures, and centro‐temporal epileptiform discharges, associated with oral and speech dyspraxia and cognitive impairment. The speech disorder was prominent, but differed from that of Landau‐Kleffner syndrome and of epilepsy with continuous spike and wave during slow‐wave sleep. The electroclinical features of this new syndrome of autosomal dominant rolandic epilepsy resemble those of benign rolandic epilepsy, a common inherited epilepsy of childhood. This family shows clinical anticipation of the seizure disorder, the oral and speech dyspraxia, and cognitive dysfunction, suggesting that the genetic mechanism could be expansion of an unstable triplet repeat. Molecular studies on this syndrome, where the inheritance pattern is clear, could also be relevant to identifying a gene for benign rolandic epilepsy where anticipation does not occur and the mode of inheritance is uncertain.
Selective expansion and long‐term culture of human schwann cells from sural nerve biopsies
Authors: Van den Berg Leonard H. , Bär Peter R. , Sodaar Peter , Mollee Isabel , Wokke John J. H. , Logtenberg Ton 
Published: January 2005

AbstractFragments of sural nerve biopsy specimens were cultured in the presence of the supernatant of lymphokine‐activated killer cells, resulting in the selective outgrowth of cells with bipolar or tripolar morphology, reminiscent of that of Schwann cells. Immunofluorescent staining with antibodies to the S‐100 protein, the low‐affinity nerve growth factor receptor, and the surface Thy‐1 antigen confirmed that these cultures contained more than 99% Schwann cells and no detectable fibroblasts. The mitotic activity of Schwann cells was measured by bromodeoxyuridine labeling, and was increased when the cells were grown in medium with lymphokine‐activated killer cell supernatant compared with medium without this supernatant. In the presence of lymphokine‐activated killer cell supernatant, Schwann cells could be maintained in continuous culture for a minimum of 8 months.
Acquired neuromyotonia: Evidence for autoantibodies directed against K+channels of peripheral nerves
Authors: Shillito Paul , Molenaar Peter C. , Vincent Angela , Leys Katherine , Zheng Wang , van den Berg Rutgeris J. , Plomp Jaap J. , Van Kempen Gertrudis Th. H. , Chauplannaz Guy , Wintzen Axel R. , van Dijk J. Gert , Newsom‐Davis John 
Published: January 2005

AbstractAcquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobulin G (IgG) from 1 neuromyotonia patient into mice increased the resistance of neuromuscular transmission tod‐tubocurarine. Here we examine nerves and muscle in vitro from mice injected with plasma or purified IgG from 6 neuromyotonia patients or pooled control subjects, and cultured dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage‐gated potassium channels labeled with125I‐α‐dendrotoxin. The quantal release of acetylcholine (quantal content) at end‐plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values (p= 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93%. The dorsal root ganglion cells treated with this IgG showed a Marchked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine‐ or α‐dendrotoxin‐sensitive K+channels in motor and sensory neurons, and they are likely to be implicated in the disease process.
Cortical control of double‐step saccades: Implications for spatial orientation
Authors: Heide W. , Blankenburg M. , Zimmermann E. , Kömpf D. 
Published: January 2005

AbstractTo accurately localize a visual target in space despite eye movement‐induced shifts of its retinal image, the brain must take into account both its retinal location and information about current eye position or at least the preceding eye displacement. We examined this ability with respect to saccadic eye movements by applying “double‐step” stimuli, where the locations of two sequentially flashed target lights have to be fixated by two successive saccades performed after their disappearance. As the 2nd saccade will not start at the spatial location from which the 2nd target was seen, a dissonance arises between its retinal coordinates and the motor coordinates of the required 2nd saccade. Nevertheless, these saccades were performed quite accurately by 32 healthy human adults. To investigate the contribution of the cerebral cortex, we recorded horizontal double‐step saccades in 35 patients with focal unilateral hemispheric lesions. Whereas frontal lesions impaired temporal properties, posterior parietal lesions caused spatial dysmetria or failure of even ipsiversive 2nd saccades following contraversive 1st saccades. This reflects an inability to compensate for retino‐spatial dissonance by using nonretinal information (corollary discharge) about eye displacement associated with a previous saccade into the contralesional hemifield. In conclusion, the parietal cortex is crucial for spatial constancy across saccades.
Effect of intensive diabetes treatment on nerve conduction in the diabetes control and complications trial
Authors:   DCCT Research Group, Box NDIC/DCCT, Bethesda, MD 20892.
Published: January 2005

AbstractThe Diabetes Control and Complications Trial demonstrated that intensive diabetes therapy effectively delays the onset of clinically apparent neuropathy in patients with insulin‐dependent diabetes mellitus. A total of 1,441 patients with insulin‐dependent diabetes mellitus were randomly assigned to receive intensive treatment or conventional treatment. Of these, 1,290 were randomized at least 41/2 years or more prior to study termination. Nerve conduction studies were performed at baseline and repeated after approximately 5 years for 1,243 of these patients, 96% of the eligible population. After 5 years of treatment, significant nerve conduction differences were observed between the intensive and conventional treatment groups, all favoring better performance (faster sensory and motor conduction velocities and shorter F‐wave latencies) in the intensive treatment group. Moreover, while performance generally deteriorated among the conventionally treated patients, most attributes remained stable or showed modest improvement in the intensively treated group. Treatment group differences were consistent across strata defined by duration of diabetes and the presence of neuropathy at baseline. A nonparametric multivariate test of all ten nerve conduction measures established a strong effect in favor of intensive treatment. These data confirm that the electrophysiological abnormalities associated with diabetic neuropathy are delayed or prevented by intensive diabetes treatment.
Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP subjects not requiring levodopa
Authors:   Parkinson Study Group
Published: January 2005

AbstractIn the controlled trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP), 310 of the 800 enrolled subjects did not reach the primary end point of disability requiring levodopa therapy during 21 ± 4 (mean ± SD) months of observation or need early initiation of deprenyl (selegiline) during a 2‐month withdrawal of experimental treatments. While maintaining the blindness of their original deprenyl and tocopherol treatment assignments, these 310 subjects were administered deprenyl 10 mglday (open label) and were monitored systematically at 1‐ to 3‐month intervals for up to 18 months (12 ±5 mo). During this extended trial, the 189 subjects who had been assigned originally to active deprenyl tended to reach the end point of disability faster than the 121 subjects who had not been assigned originally to deprenyl (hazard ratio, 1.43; 95% CI, 0.98, 2.09; p = 0.065). However, the differential rates of reaching the end point may have been due in part to the more severe baseline impairment of deprenyl‐assigned subjects, who benefited originally from deprenyl but who were more likely to require levodopa during this extended period of observation. Prior treatment with deprenyl did not lead to superior survival with respect to the end point of disability requiring levodopa, suggesting that the initial advantages of deprenyl were not sustained.
Functional imaging of human right hemispheric activation for exploratory movements
Authors: Gitelman Darren R. , Alpert Nathaniel M. , Kosslyn Stephen , Daffner Kirk , Scinto Leonard , Thompson William , Mesulam M‐Marsel 
Published: January 2005

AbstractWe employed positron emission tomography to examine the functional anatomy of the exploratory‐motor aspect of spatial attention. Subjects moved their right hand under nonexploratory (control) versus exploratory (active) conditions. Movement architecture and eye movements were matched across conditions. Statistical parametric maps of the exploratory (active) minus nonexploratory (control) tasks in subjects using their right hand in the right hemispace demonstrated activation in right cingulate, premotor and posterior parietal areas. The net activation of multiple right hemisphere cortical areas ipsilateral to the active limb and hemispace strongly supports the predicted, distributed network anatomy and is consistent with possible right hemispheric dominance for exploratory attentional movements.
Deletions of chromosome 17p11.2 in multifocal neuropathies
Authors: Tyson J. , Malcolm S. , Thomas P. K. , Harding A. E. 
Published: January 2005

AbstractWe investigated 51 patients with multifocal neuropathies for the deletion of chromosome 17p11.2 described in families with hereditary neuropathy with liability to pressure palsies (HNPP). The deletion was detected in 24 patients, including 19 patients from 14 of 15 families in whom HNPP had been considered likely on clinical, neurophysiological, and/or pathological grounds. One patient with a deletion had rather unusual clinical features for HNPP, presenting with a progressive scapuloperoneal syndrome. Overall, 7 (37%) of the 19 index patients with the deletion had no affected relatives, and less than half had evidence of a generalized neuropathy on examination. Peripheral nerve lesions were related to pressure in only 15 (62%) of the patients with the deletion. Nerve conduction studies in 23 of 25 patients and relatives studied showed a fairly uniform pattern of moderate prolongation of distal sensory and motor latencies and slowing of conduction velocities, and variable reduction of sensory or evoked muscle action potential amplitudes. The patients investigated who did not have a deletion of 17p11.2 were heterogeneous and included those with recurrent and/or familial neuralgic amyotrophy, two or more peripheral nerve lesions at common sites of entrapment, or a patchy axonal neuropathy of unknown etiology. In 1 patient a diagnosis of HNPP remains most likely. DNA analysis for the deletion of 17p11.2 is clearly useful in establishing the diagnosis of HNPP, which should be considered regardless of family history or clinical evidence of a generalized neuropathy, and in patients with multifocal neuropathies that do not conform to the classic clinical picture of HNPP.
Use of anti‐neurofilament antibody to identify paired‐helical filaments in inclusion‐body myositis
Authors: Askanas Valerie , Alvarez Renate B. , Mirabella Massimiliano , Engel W. King 
Published: January 2005

AbstractPaired‐helical filaments (PHFs) are an important diagnostic criterion of the inclusion‐body myositis (IBM) muscle biopsy; but, until now, their presence could be identified only by electronmicroscopy. In this report, we describe an easy immunocytochemical procedure, utilizing commercially available antibody, that enables reliable identification of muscle PHFs by light microscopy. This procedure greatly facilitates diagnosis of IBM.
Levodopa ethylester : A novel rescue therapy for response fluctuations in parkinson's disease
Authors: Djaldetti Ruth , Melamed Eldad 
Published: January 2005

AbstractIn Parkinson's disease (PD), response fluctuations may be due, in part, to pharmacokinetic problems including poor solubility of levodopa and difficulties in its absorption. We administered levodopa ethylester (LDEE), a new highly soluble prodrug of levodopa, by subcutaneous and intramuscular injections to PD patients with response fluctuations, in an open trial to examine its safety and efficacy. Various doses of LDEE (150–400 mg) turned patients “on” with a high success rate (43 of 45 injections). Latencies to “turning on” decreased and duration of on responses increased in a dose‐dependent manner. LDEE, given either subcutaneously or intramuscularly, produced similar beneficial effects and induced rapid and sustained elevations in plasma levodopa levels. The drug was well tolerated with only minor and negligible side effects. Study suggests that subcutaneous and intramuscular administration of LDEE may be advantageous as a novel therapeutic strategy for response fluctuations. It may be particularly useful to rapidly and predictably rescue patients from a variety of disabling “off” situations.
Spinocerebellar ataxia 3 and machado‐joseph disease: Clinical, molecular, and neuropathological features
Authors: Durr Alexandra , Stevanin Giovanni , Cancel Geraldine , Duyckaerts Charles , Abbas Nacer , Didierjean Olivier , Chneiweiss Herve , Benomar Ali , Lyon‐Caen Olivier , Julien Jean , Serdaru Michel , Penet Christiane , Agid Yves , Brice Alexis 
Published: January 2005

AbstractPatients with spinocerebellar ataxia 3 (SCA3) and Machado‐Joseph disease (MJD) carry an expanded CAG repeat in the MJDl gene. One hundred twenty families of different geographic origin with autosomal dominant cerebellar ataxia (ADCA) type I were tested. Thirty‐four families (126 patients) carried an expanded CAG repeat. The expanded and the normal allele did not overlap and the repeat was unstable during transmission, with variation in the size of the CAG length ranging from −8 to +5 and a mean expansion of 0.86 repeats without differences according to the parental sex. There was a combined effect of the number of CAG repeats of the expanded and normal allele on the age at onset, which accounted for 70% of its variability. The length of the CAG repeat influenced the frequency of clinical signs associated with cerebellar ataxia, such as abnormal tendon reflexes or decreased vibration sense, whereas the interindividual variation of supranuclear ophthalmoplegia, sphincter and swallowing difficulties, and amyotrophy was mostly determined by different disease durations. We compared the clinical profile of 91 SCA3/MJD patients with 51 SCAl and 32 SCA2 patients. There were striking differences between the SCA3/MJD and SCA2 but not with SCAl groups of patients. Despite their clinical similarities, distinct neuropathological features were observed in 2 SCA3/MJD and SCAl patients.
The response to levodopa in parkinson's disease: Imposing pharmacological law and order
Authors: Nutt John G. , Holford Nicholas H. G. 
Published: January 2005

AbstractThe seemingly unpredictable response to levodopa in patients with Parkinson's disease can be understood as an interaction between several distinct pharmacological effects of levodopa. The most important are a short‐duration response with a half‐life of minutes to hours and a long‐duration response with a half‐life of days, superimposed on diurnal motor variation. A negative response characterized by brief worsening before and after the short‐duration response and dyskinesia accentuate the short‐duration response. These various responses are modified by disease progression and long‐term levodopa therapy. Pharmacodynamic modeling of the short‐duration response indicates that with time, the response becomes less graded and small changes in levodopa concentrations can produce big changes in response. In this setting, unpredictability arises from the variation in absorption and distribution of levodopa.
Paramyotonia congenita: The R1448P Na+ channel mutation in adult human skeletal muscle
Authors: Lerche H. , Mitrovic N. , Dubowitz V. , Lehmann‐Horn F. 
Published: January 2005

AbstractTwitch force and Na+ currents were investigated in a muscle biopsy specimen from a patient with paramyotonia congenita carrying the dominant Arg‐1448‐Pro mutation in the skeletal muscle sodium channel. Cooling of the muscle fibers caused sustained membrane depolarization that resulted in reduced twitch force. Membrane repolarization, produced by a K+ channel opener, partly prevented and antagonized the drop in twitch force. Patch‐clamp recordings on sarcolemmal blebs revealed a distinctly slower Na+ current decay on paramyotonia congenita muscle compared to control muscle. In addition, patches with mutant Na+ channels showed a significantly higher frequency of steady‐state openings, which increased with cooling. Activation of mutant channels was not affected, whereas the steady‐state inactivation curve was shifted by −5 mV and showed less voltage dependence. We suggest that the weakness of cooled muscle can be explained by a combination of the increased steady‐state Na+ current and the left‐shifted inactivation curve.
Intercellular adhesion molecule‐1‐deficient mice are less susceptible to cerebral ischemia‐reperfusion lnjury
Authors: Soriano Sulpicio G. , Lipton Stuart A. , Wang Yanming F. , Xaio Min , Springer Timothy A. , Gutierrez‐Ramos Jose‐Carlos , Hickey Paul R. 
Published: January 2005

AbstractNeutrophil emigration is mediated by adhesion proteins that are highly expressed on the endothelial surface during inflammatory processes in the brain. Intercellular adhesion molecule‐1 (ICAM‐1) is an inducible adhesion molecule that binds to leukocyte integrins and facilitates neutrophil adhesion and transendothelial migration. To study the role of ICAM‐1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in ICAM‐1‐deficient mice generated by gene targeting in embryonic stem cells. Transient focal ischemia was induced by occluding the left middle cerebral artery for 3 hours followed by a 21‐ or 45‐hour reperfusion period. When compared with their wild‐type littermates, ICAM‐1‐deficient mice were less susceptible to cerebral injury as demonstrated by a 5.6‐ or 7.8‐fold reduction in infarction volume, respectively. These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and that ICAM‐1 deficiency reduces neurological damage after transient focal cerebral ischemia.
A β‐subunit mutation in the acetylcholine receptor channel gate causes severe slow‐channel syndrome
Authors: Gomez Christopher M. , Maselli Ricardo , Gammack Jason , Lasalde Jose , Tamamizu Shiori , Cornblath David R. , Lehar Mohamed , McNamee Mark , Kuncl Ralph W. 
Published: January 2005

AbstractPoint mutations in the genes encoding the acetylcholine receptor (AChR) subunits have been recognized in some patients with slow‐channel congenital myasthenic syndromes (CMS). Clinical, electrophysiological, and pathological differences between these patients may be due to the distinct effects of individual mutations. We report that a spontaneous mutation of the β subunit that interrupts the leucine ring of the AChR channel gate causes an eightfold increase in channel open time and a severe CMS characterized by severe endplate myopathy and extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.
The neuropathology of chromosome 17‐linked dementia
Authors: Sima A. A. F. , Defendini R. , Keohane C. , D'Amato C. , Foster N. L. , Parchi P. , Gambetti P. , Lynch T. , Wilhelmsen K. C. 
Published: January 2005

AbstractWe recently described a family with chromosome 17‐linked dementia, characterized clinically by disinhibition‐dementia parkinsonism‐amyotrophy complex. We report now the neuropathology of 6 affected family members. This included semiquantitative scoring of neuronal loss, gliosis, and spongiosis and immunocytochemical and ultrastructural characterization of neuronal and glial inclusions. The changes consisted of circumscribed neuronal loss, gliosis, and spongiosis of limbic neocortical areas and frontal, temporal, and occipital association areas. Similar changes were present in subcortical nuclei, most severe in the substantia nigra, but also involved the ventral striatum and amygdala. The hippocampus was spared except for degeneration of the afferent perforant tract, secondary to entorhinal nerve cell loss. Hgyrophilic neuronal inclusions, with a characteristic immunocytochemical profile, were found in brainstem nuclei, hypothalamus, and basal ganglia. Ultrastructurally, in 3 patients these inclusions showed hitherto undescribed abnormally assembled filaments. Glial cytoplasmic inclusions were widespread in white matter structures. Immunocytochemistry failed to demonstrate the protease‐resistant prion protein. The pathology appears to be unique, involving various cortical and subcortical structures, and is consistent with the clinical findings of Kliiver‐Bucy‐like syndrome, parkinsonism, and frontal lobe dementia. For this entity we suggest the term “chromosome 17‐ linked dementia”.
Evidence for anticipation and association of deletion size with severity in facioscapulohumerd muscular dystrophy
Authors: Tawil Rabi , Forrester James , Griggs Robert C. , Mendell Jerry , Kissel John , McDermott Michael , King Wendy , Weiffenbach Barbara , Figlewicz Denise ,   The FSH‐DY Group
Published: January 2005

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is characterized by marked inter and intrafamilial heterogeneity in its clinical expression. The contribution of genetic factors to this variability is not well characterized. We examined the relationship of phenotype to genotype in a clinically and genetically well‐defined FSHD population. Quantitative isometric myometry (QMT) scores, normalized for age, gender, and height, were used to quantify disease severity. We found a significant (r = 0.92, p < 0.004) correlation between disease severity and the size of the 4q35‐associated deletion. In addition, when relative disease severity of parent‐offspring pairs was compared, the offspring were found to be significantly more severely affected (p = 0.01 1). This generational effect suggests the presence of anticipation in FSHD and raises the possibility of an underlying dynamic mutation.