bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinocerebellar ataxia type 6: Gaze‐evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset
Authors: Gomez Christopher M. , Thompson Randall M. , Gammack Jason T. , Perlman Susan L. , Dobyns William B. , Truwit Charles L. , Zee David S. , Clark H. Brent , Anderson John H. 
Published: January 2005

AbstractSpinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant cerebellar ataxia associated with small expansions of the trinucleotide repeat (CAG)n in the gene CACNL1A4 on chromosome 19p13, which encodes the α1 subunit of a P/Q‐type voltage‐gated calcium channel. We describe clinical, genetic, neuroimaging, neuropathological, and quantitative oculomotor studies in four kindreds with SCA6. We found strong genetic linkage of the disease to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles in two large ataxia kindreds. The expanded alleles were all of a single size (repeat number) within the two large kindreds, numbering 22 and 23 repeat units. It is noteworthy that the age of onset of ataxia ranged from 24 to 63 years among all affected individuals, despite the uniform repeat number. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of ocular motor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibulo‐ocular reflex. These studies identify a distinct phenotype associated with this newly recognized form of dominant SCA.
Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome
Authors: Matsuishi Toyojiro , Nagamitsu Shinichiro , Yamashita Yushiro , Murakami Yoshihiko , Kato Hirohisa , Kimura Akihiko , Sakai Tetsuo , Kimura Akihiko , Percy Alan K. , Shoji Hiroshi 
Published: January 2005

AbstractTo clarify the mechanism of brain and spinal cord impairment in Rett syndrome (RS), we measured the cerebrospinal fluid (CSF) levels of substance P in 20 patients with RS including 16 childhood patients and 4 adult patients. Findings were compared with those obtained in age‐matched controls and diseased controls. The CSF level of substance P was significantly lower in patients with RS compared with controls. The alteration in the CSF level of substance P may be related to the neurological impairment, especially autonomic dysfunction, and neuropathological involvement of dorsal root ganglia and peripheral nerve observed in RS.
Extratemporal atrophy in patients with complex partial seizures of left temporal origin
Authors: Decarli C. , Hatta Junko , Fazilat Shahram , Fazilat Shahin , Gaillard W. D. , Theodore William H. 
Published: January 2005

AbstractTotal cerebral, temporal lobe, hippocampal, caudate, and lenticular nuclei volumes were quantified from magnetic resonance images of 21 patients with left temporal lobe epilepsy and medically intractable complex partial seizures. These regional brain volumes were compared with the same measures in 19 controls. No significant differences in total cerebral, left temporal lobe, right temporal lobe, or total temporal lobe volumes were found. As expected, left hippocampal volumes were significantly smaller in the patients with epilepsy than in control subjects. The left hippocampus‐to‐right hippocampus volume ratio was significantly lower in patients than in control subjects. In addition to left hippocampal volumes, mean left thalamic, left caudate, and bilateral lenticular volumes were significantly smaller in the patients with epilepsy than in control subjects. The left‐to‐right thalamic volume ratio was also significantly lower in the patients with epilepsy compared with control subjects, but there were no significant group differences in caudate or lenticular ratios. These results show that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. The pathophysiological significance of our findings is uncertain. They could be related to the underlying cause of the disorder. However, volume loss also may reflect damage due to involvement of these structures in recurrent seizure activity.
Narcolepsy in prepubertal children
Authors: Guilleminault Christian , Pelayo Rafael 
Published: January 2005

AbstractNarcolepsy was diagnosed in 51 children (29 boys). The age range was 2.1 to 11.8 years (mean, 7.9 ± 3.1 years). A mean of three referrals was made before narcolepsy was considered. In 10 children, cataplexy was the presenting symptom. Thirty‐eight children acknowledged sleep paralysis and 30 acknowledged hypnagogic hallucinations. All children had sleep studies; 31 exhibited rapid eye movement at sleep onset. The mean sleep latency was 1.5 minutes ± 39 seconds on the Multiple Sleep Latency Test. All children had at least two sleep‐onset rapid eye movement sleep episodes in this test. Forty‐six children were HLA class II–positive for DQw6, and 45 were also positive for DRw15. Thirty (65%) families refused referrals to support and counseling groups. Teachers often refused to acknowledge a medical problem. During follow‐up, all children presented at least once with depressive symptoms in reaction to their syndrome. Narcolepsy should be considered when evaluating children with behavioral and depressive symptoms.
Hyponatremia due to sodium valproate
Authors: Branten A. J. W. , Wetzels J. F. M. , Weber A. M. , Koene R. A. P. 
Published: January 2005

AbstractWe describe a 50‐year‐old male patient with hyponatremia (serum sodium level, 128 mEq/L) discovered during routine follow‐up for Henoch‐Schönlein nephritis. The patient was known to have a generalized idiopathic epilespsy and was on 2,000 mg/day of sodium valproate. After exclusion of other causes such as hypothyroidism and adrenal insufficiency, we considered sodium valproate as the cause of the hyponatremia. Repeated water loading tests performed at different dosages of this drug confirmed that the ability to excrete water was reduced in a dose dependent manner. We conclude that sodium valproate can cause an SIADH‐like syndrome with hyponatremia and that serum sodium levels have to be monitored during treatment with high dosages of this drug.
Low numbers and no loss of melanized nigral neurons with increasing age in normal human brains from India
Authors: Muthane Uday , Yasha T. C. , Shankar S. K. 
Published: January 2005

AbstractThe prevalence of Parkinson's disease (PD) is higher in whites than in nonwhites and it increases with advancing age. The pathological hallmarks of PD are loss of pigmented neurons in the substantia nigra pars compacta (SNpc) and presence of Lewy bodies. With increasing age, a similar loss of pigmented neurons in the SNpc has been reported. Hence, age and race possibly play a role in the pathogenesis of PD. The objectives of this study were to count the number of melanized neurons in the SNpc in normal human brains from India and study the change in neuronal count with advancing age and to compare the neuronal counts from this Indian population with counts reported in normal brains from the United Kingdom. Melanized neurons in the SNpc were counted in 84 normal human brains (age range, 5–84 years) in a single 7‐μm section at the level of emergence of the oculomotor nerve. In the brains from India, there was no loss of melanized nigral neurons with advancing age. The absolute number of these melanized neurons was about 40% lower than the brains from UK. Despite a low number of melanized nigral neurons in the brains from India, individuals function normally and have dopamine levels comparable with their Western counterparts, suggesting that it is not the absolute number of melanized nigral neurons but the percent loss of nigral neurons that results in dopaminergic deficiency in PD. There is no significant loss of pigmented nigral neurons with age, suggesting that the loss seen in PD is exclusively due to the disease process itself. Indians have a lower prevalence of PD despite having a low count of melanized nigral neurons, suggesting that better protective mechanisms may be present in the Indians to prevent the loss of nigral neurons.
Mutations in all five exons of SOD‐1 may cause ALS
Authors: Shaw C. E. , Enayat Z. E. , Chioza B. A. , Al‐Chalabi A. , Radunovic A. , Powell J. F. , Leigh P. N. 
Published: January 2005

AbstractEight of 38 patients (21%) with familial and 5 of 175 patients (3%) with sporadic amyotrophic lateral sclerosis (ALS) had missense mutations in the SOD‐1 gene. Two novel mutations were identified. One in exon 4 substituting leucine with phenylalanine (L84F) in a familial patient and the second in exon 3 at substituting glycine with serine (G72S) in an “apparently” sporadic patient. Over 60 point mutations have now been described in all five exons of SOD‐1, involving 43 of the 153 residues. Hypotheses about the toxic role of mutant SOD‐1 in the pathogenesis of ALS must account for this molecular diversity.
Low frequency of α‐synuclein mutations in familial Parkinson's disease
Authors: Farrer Matt , Wavrant‐De Vrieze Fabienne , Crook Richard , Boles Lizzie , Perez‐Tur Jordi , Hardy John , Johnson William G. , Steele John , Maraganore Demetrius , Gwinn Katrina , Lynch Tim 
Published: January 2005

AbstractA mutation in exon 4 of the α‐synuclein (NACP) gene has been reported to explain the chromosome 4 linkage to autosomal dominant Parkinson's disease. We developed primers and methods for exonic sequencing of this gene and sequenced the entire coding region of the gene in 6 families with autosomal dominant disease and in 2 cases of lytico and bodig from Guam. In addition, we have sequenced exon 4 of this gene in 5 cases of familial disease and have screened for the specific mutation (A53T) in a 40 cases of idiopathic Parkinson's disease, 3 cases of multisystem atrophy, and 15 cases of Lewy body dementia. We have found no genetic variation in the gene. We discuss these findings with respect to both the epidemiology of Parkinson's disease and the possibility that NACP is not the chromosome 4 locus for disease.
Epilepsies in twins: Genetics of the major epilepsy syndromes
Authors: Berkovic Samuel F. , Howell R. Anne , Hay David A. , Hopper John L. 
Published: January 2005

AbstractWe studied twins to examine the genetics of epilepsy syndromes. We ascertained 358 twin pairs in whom one or both reported seizures. After evaluation, 253 of 358 (71%) had seizure disorders and 105 pairs were false positives. Among the monozygous (MZ) pairs, more were concordant for seizures (48 of 108; casewise concordance = 0.62 ± 0.05) than among the dizygous (DZ) pairs (14 of 145; casewise concordance = 0.18 ± 0.04). In 94% of concordant MZ pairs, and 71% of concordant DZ pairs, both twins had the same major epilepsy syndrome. When analyzed according to major epilepsy syndrome, the casewise concordances for generalized (MZ = 0.82; DZ = 0.26), both idiopathic (MZ = 0.76; DZ = 0.33) and symptomatic (MZ = 0.83; DZ = 0), were greater than those for partial epilepsies (MZ = 0.36; DZ = 0.05), with intermediate values seen for febrile seizures (MZ = 0.58; DZ = 0.14) an dunclassified epilepsies (MZ = 0.53; DZ = 0.18). We conclude that genetic factors are particularly important in the generalized epilepsies but also play a role in the partial epilepsies. The high frequency of concordant MZ pairs with the same major syndrome strongly suggets there are syndrome‐specific genetic determinants rather than a broad genetic predisposition to seizures.
Clinical demographics of multiplex families with multiple sclerosis
Authors:   Multiple Sclerosis Genetics Group
Published: January 2005

AbstractThe demographic and clinical characteristics of 89 multiplex families whose affected members meet proposed diagnostic criteria for multiple sclerosis (MS) genetic research are described and compared with 425 sporadic cases of MS and other published collections of MS multiplex families. The proportion of affected multiplex family members who experienced gradual progression of disability from onset (primary progressive MS) is lower than reported by other investigators. Different phenotypes of MS may reflect genetic heterogeneity that may partially explain inconsistencies in the results of genetic linkage studies. Clinical details of affected multiplex family members must be described so that comparisons of genetic results across studies can be properly interpreted.
Modification of levodopa responses by deprenyl (selegiline): An electrophysiological and behavioral study in the rat relevant to Parkinson's disease
Authors: Mercuri Nicola B. , Scarponi Mariangela , Federici Mauro , Bonci Antonello , Siniscalchi Antonio , Bernardi Giorgio 
Published: January 2005

AbstractFrom using in vitro intracellular recordings from mesencephalic neurons and monoamine‐depleted rats, we report that the functions of levodopa in the brain are greatly enhanced and prolonged by high does of the monoamine oxidase (MAO) inhibitor deprenyl. Dopaminergic neurons were hyperpolarized and inhibited by levodopa application. These effects of levodopa were largely potentiated by pretreatment with nonselective does of deprenyl. Furthermore, when locomotor activity induced by levodopa was examined on a rodent model of parkinson's disease, pretreatment of the animals with nonselective doses of deprenyl caused an enhancement of the antiparkinsonian action of levodopa. The great increase in levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine precursor with a higher dosage of the MAO inhibitor, to reduce effectively the daily levodopa requirements in Parkinson's disease patients.
Neurological and neuroradiological findings in long‐term survivors of allogeneic bone marrow transplantation
Authors: Padovan Claudio S. , Yousry Tarek A. , Schleuning Michael , Holler Ernst , Kolb Hans‐Jochem , Straube Andreas 
Published: January 2005

AbstractThe aim of this study was to assess neurological, neuropsychological, and neuroradiological findings in long‐term survivors of allogeneic bone marrow transplantation (BMT) who were recruited from a hematological outpatient clinic. In addition, risk factors for the development of late neurological complications were identified. In contrast to previous studies on autopsied patients, our study design provoked a bias away from increased neurological sequelae, because patients with early complications after BMT were excluded. Fifty‐nine allogeneic patients and 7 autologous BMT patients underwent clinical examination, short neuropsychological testing, and cranial magnetic resonance imaging (MRI) 34 ± 26 months after BMT. The pathological results of the neurological examination (abnormal 64%) and the MRI examination (white matter lesions, 54%; atrophy, 11%) were associated with the occurrence of chronic graft‐versus‐host disease (GvHD) evolving from acute GvHD, with corticosteroid therapy and with cyclosporine medication. Neuropsychological impairment (cognitive deficits, 37%) was associated with long‐term cyclosporine medication and age. No influence of pre‐BMT disease, BMT donor status, or the conditioning regimen was found. These results suggest that the frequent neurological abnormalities in long‐term survivors of allogeneic BMT are associated with chronic GvHD and with the resulting immunosuppression as major risk factors.
High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa‐responsive dystonia
Authors: Steinberger D. , Weber Y. , Korinthenberg R. , Deuschl G. , Benecke R. , Martinius J. , Müller U. 
Published: January 2005

AbstractWe performed a clinical and molecular genetic analysis in members of five families with dopa‐responsive dystonia. Four mutations were detected in the gene GCH1 that codes for GTP cyclohydrolase I. Two of these mutations, a delG309 in exon I and a C544T transition in exon 5, have not been described before. They result in inactivation of the enzyme by truncation. The remaining two mutations, both A to G transitions, a(−2)g in intron I and a(−2)g in intron 2, cause truncation by abnormal splicing. The genotype of family members was correlated to their clinical phenotype (obtained before molecular analysis). Clinical symptoms observed in the families included generalized and focal dystonia, abnormal gait, and subtle signs such as an abnormal writing test. High penetrance (0.8–1.0) was observed in four of five families if minor symptoms and signs were considered. A given mutation was more likely to cause symptoms in females than in males, thus confirming the well‐established higher incidence of dopa‐responsive dystonia in females than in males.
Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils
Authors: Rosenbaum Daniel M. , D'Amore Jason , Llena Josefina , Rybak Susan , Balkany Adam , Kessler John A. 
Published: January 2005

AbstractThe goal of this study was to determine whether aurintricarboxylic acid (ATA), an endonuclease inhibitor known to inhibit apoptosis, could ameliorate cell damage in a gerbil model of transient ischemia. Transient ischemia. Transien ischemia was induced in gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four micrograms of ATA was administered intraventricularly I hour before ischemia, and the brains were assessed histologically 1 week later to quantitate cell loss in the vulnerable CA‐1 subsector of the hippocampus. In a separate set of experiments, 4 μg of ATA was administered intraventricularly 1 hour before ischemia and the brains were assessed for evidence of DNA fragmentation by the TUNEL method. There was only a 16% cell loss compared with nonischemic controls in animals pretreated with ATA that was significantly less (p < 0.05) than the 48% cell loss in animals pretreated with saline alone. TUNEL‐positive cells were first evident at 3 days and were still present at 7 days subsequent to ischemia. Maximal staining occurred at 4 days. Pretreatment with ATA virtually eliminated TUNEL staining at 4 days. These results support the hypothesis that the delayed cell death secondary to transient ischemia is, in part, apoptotic. Furthermore, ATA afforded significant neuronal protection and prevented DNA fragmentation.
Sleep apnea in patients with postpolio syndrome
Authors: Dean Andy C. , Graham Bonnie A. , Dalakas Marinos , Sato Susumu 
Published: January 2005

AbstractWe studied sleep architecture and sleep apnea pattern in patients with postpolio syndrome (PPS). Ten patients with clinical signs of PPS underwent polysomnographic recording for two consecutive nights. Although sleep efficiency and proportions of sleep stages were within the normal range, sleep architecture was disrupted owing to sleep apnea. Patients with bulbar involvement had more frequent sleep apnea (mean sleep apnea index, 11.09) than patients without (apnea index, 5.88). The former also had significantly more central apnea, which occurred more commonly during non‐rapid‐eye‐movement (NREM) than rapid‐eye‐movement (REM) sleep, than those without bulbar signs. This finding suggests reduction in forebrain control of compromised bulbar respiratory centers during NREM sleep in PPS.
The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury
Authors: Yamada Kelvin A. , Covey Douglas F. , Hsu Chung Y. , Hu Rong , Hu Yuefei , He Yong Y. 
Published: January 2005

AbstractThe diazoxide derivative IDRA 21 and other positive modulators of (AMPA)‐type glutamate receptors are considered potential memory‐enhancing agents. However, AMPA receptor activation contributes to CA1 hippocampal neuron damage from global ischemia in rodents, raising the possibility that 7‐chloro‐3‐methyl‐3‐4‐dihydro‐2H‐1,2,4 benzothiadiazine S, S‐dioxide (IDRA 21) or drugs with similar actions may worsen ischemic neuronal injury. Here we demonstrate that glutamate plus IDRA 21 kills cultured rat hippocampal neurons by AMPA receptor activation, and, in vivo, 12 and 24 mg/kg of IDRA 21 given orally increases CA1 neuron loss produced by 10 minutes of global ischemia. Treating patients with drugs that potentiate AMPA receptor activation will have to consider these potential effects, particularly when coexistent with conditions in which excessive activation of AMPA receptors may occur (eg, stroke, seizures).
Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors
Authors: Liedtke Wolfgang , Cannella Barbara , Mazzaccaro Richard J. , Clements John M. , Miller Karen M. , Wucherpfenning Kai W. , Gearing Andrew J. H. , Raine Cedric S. 
Published: January 2005

AbstractThe proinflammatory Th1 cytokine, tumor necrosis factor‐α (TNFα), the cell death signaling molecule FasL, and several extracellular matrix degrading metalloproteinases have been implicated in the pathogenesis of multiple sclerosis (MS). The latter enzymes, as well as TNFα‐converting enzyme and FasL‐converting enzyme, can be blocked by matrix metalloproteinase inhibitors (MMPIs). In this study, we show that a potent MMPI was clinically effective in an animal model for MS, experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse. Efficacy was remarkable, as indicated by blocking and reversal of acute disease and reduced number of relapses and diminished mean cumulative disease score in chronic relapsing animals. Also, demyelination and glial scarring were significantly decreased in MMPI‐treated mice with chronic relapsing EAE, as was central nervous system gene expression for TNFα and fasL. It is interesting that expression of the beneficial cytokine interleukin‐4 (IL‐4) was increased, and IL‐4 was expressed on glial cells. The relevance of these compounds for MS was underscored by their ability to specifically inhibit TNFα shedding and cytotoxicity of myelin‐autoreactive human cytotoxic CD4+ T‐cell clones. This is the first report to show a positive effect by MMPIs on chronic relapsing EAE, its central nervous system cytokine profile, and on TNFα shedding by human myelin‐autoreactive T cells.
Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions
Authors: Krings Timo , Chiappa Keith H. , Cuffin B. Neil , Buchbinder Bradley R. , Cosgrove G. Rees 
Published: January 2005

AbstractWe evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of divrse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptognic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three‐dimensional data not available from conventional analysis.