bluuebunny/crossref_metadata_2025 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

Spinocerebellar 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

To 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

Total 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

Narcolepsy 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

We 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

The 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

Eight 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

A 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

We 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

The 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

From 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

The 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

We 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

The 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

We 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

The 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

The 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

We 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.
Association of α1‐antichymotrypsin polymorphism with cerebral amyloid angiopathy
Authors: Yamada Masahito , Sodeyama Nobuyuki , Itoh Yoshinori , Suematsu Naomi , Otomo Eiichi , Matsushita Masaaki , Mizusawa Hidehiro
Published: January 2005

In search of genetic risk factors of sporadic cerebral amyloid angiopathy (CAA), we investigated the association of a polymorphism in the signal peptide sequence of α1‐antichymotrypsin (ACT) with the severity of CAA in 155 autopsy cases of the elderly, including 48 patients with Alzheimer's disease. In the total cases, there was no significant association of the ACT genotypes (AA, AT, and TT) with the severity of CAA. Within the Alzheimer's disease group, however, a significant correlation was found between the ACT A allele frequency and the severity of CAA.
Normal serum iron and ferritin concentrations in patients with Friedreich's ataxia
Authors: Wilson Robert B. , Lynch David R. , Fischbeck Kenneth H.
Published: January 2005

Friedreich's ataxia (FRDA) is caused by point mutations or trinucleotide repeat expansions in both alleles of the gene encoding frataxin. Studies of frataxin homologues in lower eukaryotes suggest that mitochondrial iron accumulation may underlie the pathophysiology of FRDA. To evaluate the possible role of iron‐chelation therapy for FRDA, we measured serum iron and ferritin concentration in 10 FRDA patients. The measurements were within normal limits, suggesting that iron‐chelation therapy for FRDA may be problematic.
Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging
Authors: Volkow N. D. , Wang G. J. , Fowler J. S. , Ding Y. S. , Gur R. C. , Gatley J. , Logan J. , Moberg P. J. , Hitzemann R. , Smith G. , Pappas N.
Published: January 2005

Aging of the human brain is associated with a decline in dopamine (DA) function, generally interpreted as reflecting DA cell loss. Postitron emission tomography studies revealed that in healthy individuals, the age‐related losses in DA transporters (presynaptic marker) were associated with losses in D2 receptors (postsynaptic marker) rather than with increases as is known to occur with DA cell loss. This association was specific for DA synaptic markers, because they were not correlated with striatal metabolism. Furthermore, the association was independent of age, suggesting that a common mechanism regulates the expression of receptors and transporters irrespective of age.
Hippocampal developmental changes in patients with partial epilepsy: Magnetic resonance imaging and clinical aspects
Authors: Baulac Michel , De Grissac Nathalie , Hasboun Dominique , Oppenheim Catherine , Adam Claude , Arzimanoglou Alexis , Semah Franck , Lehéricy Stephane , Clémenceau Stephane , Berger Brigitte
Published: January 2005

Developmental disorders of the hippocampal formation (HF) have been described in epileptic syndromes associated with lissencephaly, but HF malformations can be found without widespread cortical changes. We report 19 patients with partial epilepsy and abonormal HF patterns on magnetic resonance imaging (MRI). The changes consisted of incomplete folding with abnormal medial location along the choroid fissure, globular shape and/or verticalization, and were observed in the following three contexts: (1) diffuse disorder of neuronal migration (n = 1); (2) temporal lobe malformation (n = 5), including heterotopia, abnormal gyration, and, in 2 cases, reduced HF volume; and (3) apparently isolated HF changes (n = 13, bilateral in 3 cases). The clinical features were heterogeneous in terms of severity of epilepsy and, when the focus could be determined, in localization (temporal or extratemporal). In 4 patients with apparently isolated HF changes, MRI was suggestive of both abnormal development and hippocampal sclerosis. In these patients, presurgical investigation and postoperative results suggested multiple epileptogenic foci, involving the frontal lobes in 2 cases. One HF specimen was large enough for the observation of developmental abnormalities corresponding to the canges seen on MRI. HF changes in shape and/or position should be included among the structural abnormalities associated with partial epilepsies. They may represent the visible part of a more extensive or more distant disorder of brain development.
Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: A pediatric oncology group study
Authors: Duffner Patricia K. , Krischer Jeffrey P. , Horowitz Marc E. , Cohen Michael E. , Burger Peter C. , Friedman Henry S. , Kun Larry E. ,   And The Pediatric Oncology Group
Published: January 2005

Between 1986 and 1990, the Pediatric Oncology Group conducted a study in which 198 children younger than 3 years of age with malignant brain tumors were treated with prolonged postoperative chemotherapy in an effort to delay irradiation and reduce long‐term neurotoxicity. Children younger than 2 years of age received 24 months of chemotherapy followed by irradiation, and those between 2 and 3 years of age received 12 months of chemotherapy plus irradiation. Chemotherapy was given in 28‐day cycles (AAB, AAB), with cycle A = vincristine (0.065 mg/kg) intravenously on days 1 and 8 and cyclophosphamide (65 mg/kg) intravenously on day 1, and cycle B = cisplatinum (4 mg/kg) intravenously on day 1 and etoposide (6.5 mg/kg) intravenously on days 3 and 4. Five of the 198 children developed second malignancies, with a cumulative risk at 8 years of 11.3% (95% confidence interval [CI], 0–39%). Four of the five second malignancies occurred in children younger than 2 years of age at diagnosis, with a cumulative risk at 8 years of 18.9% (CI, 0–70%). Initial diagnoses were choroid plexus carcinoma (2 children), ependymoma (1 child), desmoplastic infantile ganglioglioma (2 children), and medulloblastoma (1 child). Duration from diagnosis of initial tumor to second malignancy was 33, 35, 57, 66, and 92 months. Three children younger than 2 years of age developed Iymphoproliferative disease, that is, myelodysplastic syndrome (2 children), both with monosomy 7 deletions, and acute myelogenous leukemia (1 child), after 24 to 26 cycles of chemotherapy, including 8 cycles of etoposide. Two of 3 received craniospinal irradiation (2,560/3,840 cGy) and (3,520/5,320 cGy). Time to second malignancy was 7 years 8 months, 4 years 9 months, and 2 years 9 months. Two children developed solid tumors, at 5 years 6 months and 2 years 11 months, respectively, after initiation of treatment. A sarcoma developed after 26 cycles of chemotherapy and no irradiation, and a meningioma developed after 12 cycles of chemotherapy and local craniospinal irradiation. Potential causative factors for this high rate of secondary malignancies include prolonged use of alkylating agents and etoposide with or without irradiation.
Overexpression of copper/zinc superoxide dismutase: A novel cause of murine muscular dystrophy
Authors: Rando Thomas A. , Crowley Rebecca S. , Carlson Elaine J. , Epstein Charles J. , Mohapatra Pramit K.
Published: January 2005

Oxidative injury underlies the cellular injury and cell death in a variety of disease states. In muscular dystrophies, evidence from in vivo and in vitro studies suggests that muscle degeneration may be secondary to an increased susceptibility to oxidativ stress. To address the role of free radical metabolism in the pathogenetic process of muscular dystrophies, we examined the muscle of transgenic mice that overexpress copper/zinc (Cu/Zn) superoxide dismutase. Overexpression of this enzyme can sensitize cells to oxidative injury, and Cu/Zn superoxide dismutase activity was elevated approximately fourfold above control levels in skeletal muscle of the transgenic strain. Examination of serum creatine phosphokinase levels in these mice revealed significant elevations after 2 months of age, indicative of active muscle breakdown. By 8 months of age, there was gross atrophy of the quadriceps muscle, and other hindlimb muscles were variably affected. Histologically, there was evidence of widespread muscle necrosis and regeneration, fiber splitting, and replacement of muscle with adipose and fibrous connective tissue, typical of a muscular dystrophy. Associated with the development of this degeneration was an increase in the levels of lipid peroxidation in the muscle of Cu/Zn superoxide dismutase transgenic mice, highlighting the central role of oxidative injury in this pathogenetic process. These results demonstrate that oxidative damage can be the primary pathogenetic process underlying a muscular dystrophy.
Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synuclein
Authors: Tu Pang‐hsien , Galvin James E. , Baba Minami , Giasson Benoit , Tomita Taisuke , Leight Susan , Nakajo Shigeo , Iwatsubo Takeshi , Trojanowski John Q. , Lee Virginia M.‐Y.
Published: January 2005

Recently, α‐synuclein was shown to be a structural component of the filaments in Lewy bodies (LBs) of Parkinson's disease (PD), dementia with LBs (DLB) as well as the LB variant of Alzheimer's disease, and this suggests that α‐synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether α‐synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected α‐synuclein, but not β‐ or γ‐synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, α‐synuclein–positive GCIs were restricted to oligodendrocytes, and α‐synuclein accumulated selectively in MSA white matter with α‐synuclein–positive GCIs. Taken together with evidence that LBs contain insoluble α‐synuclein, our data suggest that a reduction in the solubility of α‐synuclein may induce this protein to form filaments that aggregate into cytoplasmic inclusions, which contribute to the dysfunction or death of glial cells as well as neurons in neurodegenerative disorders with different phenotypes.
Seizure outcome after epilepsy surgery in children and adolescents
Authors: Wyllie Elaine , Comair Youssef G. , Kotagal Prakash , Bulacio Juan , Bingaman William , Ruggieri Paul
Published: January 2005

Few epilepsy surgery outcome data are available from series of pediatric patients. We studied seizure outcome in 136 pediatric patients who had surgery for intractable epilepsy at The Cleveland Clinic between January 1990 and June 1996, with a postoperative follow‐up of 1 to 7.5 years (mean, 3.6 years). Sixty‐two children (3 months to 12 years old at time of surgery) were compared with 74 adolescents (13–20 years old). Extratemporal or multilobar resections and hemispherectomies were similarly frequent among children (50%) and adolescents (44%), but these procedures strongly predominated in infancy (90% of patients 0–2 years of age). The remaining patients had temporal resection. Cortical dysplasia and low‐grade tumor were the most common causes and hippocampal sclerosis was rare. Seizure‐free outcome was achieved for 69% of adolescents, 68% of children, and 60% of the infant subgroup, overall; for 23 (74%) of 31 children and 33 (80%) of 41 adolescents after temporal resection; for 11 (58%) of 19 children and 15 (52%) of 29 adolescents after extratemporal or multilobar resection; and for 8 (67%) of 12 children and 3 (75%) of 4 adolescents after functional hemispherectomy. Seizure‐free outcome was more frequent after temporal resection (56 of 72, 78%) than after extratemporal or multilobar resection (26 of 48, 54%; 41 of 48 with a focal lesion on magnetic resonance imaging), and among patients with tumor (36 of 44, 82%) versus cortical dysplasia (16 of 31, 52%). The frequency of seizure‐free outcome after epilepsy surgery was similar for infants, children, and adolescents, and comparable with results from adult series. Most patients in each age, surgery type, and causal group were free from seizures after surgery. These results suggest that children should be considered for surgical evaluation at whatever age they manifest with severe, intractable, disabling localization‐related epilepsy.
Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage
Authors: Oaklander Anne Louise , Romans Katharine , Horasek Sylvia , Stocks Adelaine , Hauer Peter , Meyer Richard A.
Published: January 2005

Shingles can cause chronic neuropathic pain (postherpetic neuralgia) long after skin lesions heal. To investigate its causes, we quantitated immunolabeled sensory neurites in skin biopsies from 18 subjects with and 16 subjects without postherpetic neuralgia after unilateral shingles. Subjects rated the intensity of their pain. Punch skin biopsies were evaluated from the site of maximum pain or shingles involvement, the homologous contralateral location, and a site on the back, distant from shingles involvement. Sections were immunostained with anti‐PGP9.5 antibody, a pan‐axonal marker, and the density of epidermal and dermal neurites determined. The group with postherpetic neuralgia had a mean density of 339 ± 97 neurites/mm2 in shingles‐affected epidermis compared with a density of 1,661 ± 262 neurites/mm2 for subjects without pain. Neurite loss was more severe in epidermis than dermis. Unexpetedly, the lack of contralateral shingles eruptions or pain, correlated epidermis. Contralateral damage ocurred despite the lack of contralateral shingles eruptions or pain, correlated with the presence and severity of ongoing pain at the shingles site, and did not extend to the distant site. Thus, the pathophysiology of postherpetic neuralgia pain may involve a new bilateral mechansm.
Abnormal somatosensory homunculus in dystonia of the hand
Authors: Bara‐Jimenez William , Catalan Maria Jose , Hallett Mark , Gerloff Christian
Published: January 2005

Abnormalities of the sensory system have been proposed as causative factors for dystonia. By mapping the human cortical hand somatosensory area of 6 patients with focal dystonia of the hand, we found an abnormality of the normal homuncular organization of the finger representations in the primary somatosensory cortex (S1). Although a remote antecedent event or even a developmental anomaly cannot entirely be ruled out, our findings may support the concept that abnormal plasticity is involved in the development of dystonia.
The nervus facialis of the albino mouse
Authors: Rhinehart D. A.
Published: January 2005

The facial nerve of the mouse corresponds very closely to that of other mammals and man, and more closely resembles the glossopharyngeal than any of the other cranial nerves. It consists of two parts: one part made up of those fibers which arise inthe motor nucleus and form the motor part of the nerve, the other part being formed by the'nervus intermedius and its peripheral continuation.
Application of the Marchi method to the study of the radix mesencephalica trigemini in the guinea‐pig
Authors: Allen William F.
Published: January 2005

The results of the previous experiments confirm May and Horsley's conclusions that the mesencephalic trigeminal root contains both ascending and descending fibers. The former take origin from sensory cells in the semilunar ganglion and the latter from globular, unipolar cells in the alar (sensory) plate of the mesencephalon, and from a caudal continuation of these cells, known as the locus. coeruleus, which extend downward into the motor area of the pons.
A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization
Authors: Ellis Robert S.
Published: January 2005

The main purpose of this paper was to show the numerical differences in Purkinje cells in normal, subnormal, and senescent cerebella.
The effect of over‐activity on the morphological structure of the synapse
Authors: Marui Kiyoyasu
Published: January 2005

Careful investigation of the cell body as well as the synapse of the fatigued Mauthner cell in Ameiurus revealed a number of interesting findings, which can be summarized as follows: The cell body was found either swollen or shrunken; the turgescence was regarded as the result of overactivity and the shrinkage as that, of exhaustion. The Nissl substance was in a more or less advanced stage of chromatolysis and thereby the cytoplasm was stained variously deeply. On the border of the nucleus a mass of stainable substance was observed as the restitution phenomenon of the Nissl bodies op the side of the nucleus. It was also accepted that a mutual interchange of substance occurs between nucleus and protoplasm in activity. The nucleus was also either swollen or shrunken; in the swollen nerve cell it was sometimes renioved to one side of the cell body. The nucleolus mas also found swollen sometimes and other times shrunken and it was of angular or otherwise irregular shape.
A retinal mechanism of efficient vision
Authors: Arey Leslie B.
Published: January 2005

The threshold of stimulation of the visual rods and cones and of the retinal pigment, a t which they exhibit their characteristic photomechanical changes, is high.
The distribution of sympathetic nerve fibers to the hind limb of the cat
Authors: Burns B. I.
Published: January 2005

In six cats the trunks of the third or fourth lumbar to the third sacral nerves were cut between the dorsal root ganglion and the gray ramus. Studies were made of serial sections of the nerve trunks with their intact gray rami, sections of the peripheral nerves, including most of the motor and sensory nerves of the posterior limb, and serial sections of the blood vessels. The latter were cut into segments and the serial sections made of each segment. IN addition, similar studies of a large number of normal vessels were made.
A study of the red nucleus in the rhesus monkey. Anatomic degenerations and physiologic effects resulting from localized lesions of the red nucleus
Authors: Carpenter Malcolm B.
Published: January 2005

No Abtract.
Myelin sheath during degeneration and regeneration. II. Histochemistry
Authors: Noback Charles R. , Reilly James A.
Published: January 2005

The histochemical properties of the myelin sheath and its fragmentation products of Wallerian degeneration are described as visualized in the normal and degenerating peripheral nerves of the monkey, cat and rat.
The human posterior commissure
Authors: Tomasch Joseph
Published: January 2005

Midline cross‐sections of the posterior commissures of five adult males were used for a determination of their cross‐sectional area and fiber‐density. Due to non‐uniform fiber‐size distribution a stratified sample involving from 12–20 areas was collected from each case. A mean cross‐sectional area of 3,587 mm2 with a standard variation of ±0.820 mm2 was measured for the five cases. Fiber density was found to vary in the different strata between 86,400 to 432,000 ± 10% per mm2 on axon counts taken from sections stained by Häggqvist's method. Counting myelin sheaths on sections stained by Weigert's method fiber density varied from 40,000 to 158,400 fibers per mm2 ± 30%. Using these values for calculating a total fiber number estimate, based on the axon count, fiber number varies from 504,566 to 887,849 fibers. Comparing this total fiber estimate with a similar estimate taken from the anterior commissure, the figure appears low. This difference is due to the presence of a great number of large diameter fibers in the posterior commissures, not found in either the anterior commissure or the corpus callosum. Attaching a probability level of t0.05 to this sample of five cases, a hypothetical posterior commissure may be expected to have a cross‐sectional area of 3.587 ± 0.942 mm2 and from 497,404 to 1,090,270 fibers. In one case the habenular commissure was also studied and found to contain 112,706 fibers (cross‐sectional area 0.697 mm2).
A trigeminal midbrain‐cerebellar fiber connection in the rat
Authors: Cupédo R. N. J.
Published: January 2005

Cerebellar collaterals of the mesencephalic trigeminal root have been studied by the use of various histologic techniques in adult and fetal brains of rat and mouse. In addition, brains of rats with lesions in the mesencephalic trigeminal system were studied.

Cells of the mesencephalic trigeminal system can be found in the brachium conjunctivum near the cerebellar hilus in the adult and fetal rat and in the fetal and full‐term mouse. Such cells located in the anterior medullary velum were found in fetal rat material and m the human brain stem. In the rat collaterals of the mesencephalic trigeminal root course through the brachium conjunctivum and anterior medullary velum, terminating in the nodulus cerebelli and possibly also in the neighborhood of the primary fissure. These fibers coursing through the anterior medullary velum decussate and intermingle with fibers of the ventral spino‐cerebellar tract and fibers of the trochlear nerve. They course ventrally from the tectocerebellar tract, which consists of smaller myelinized fibers. Termination in the cerebellum is by means of mossy fibers. The findings are discussed as they relate to previous studies.

It is probable, that the cerebellum utilizes proprioceptive impulses conducted by mesencephalic fifth fibers in its coordinating influence on the activity of the muscles of mastication.
Sites and mode of termination of reticulo‐spinal fibers in the cat. An experimental study with silver impregnation methods
Authors: Nyberg‐hansen Rolf
Published: January 2005

Following lesions in the brain stem reticular formation in 20 cats the ensuing degeneration within the spinal cord has been studied with silver impregnation methods with special reference to the laminar organization of the gray matter described by Rexed ('52, '54).

Reticule‐spinal fibers do not arise in the mesencephalon. Pontine reticulo‐spinal fibers descend in the ventral funiculus, almost exclusively homolaterally. Some cross to the contralateral side in the anterior commissure. Medullary reticulo‐spinal fibers descend bilaterally in the ventral part of the lateral funiculus, mostly homolaterally. Both contingents of fibers descend the whole cord throughout. Pontine reticulo‐spinal fibers are more numerous than medullary ones.

Pontine fibers terminate bilaterally in lamina VIII and adjacent parts of lamina VII. Contralateral terminations are established mainly by way of fibers crossing in the anterior commissure. Medullary fibers terminate chiefly in lamina VII. A few terminations are found in lamina IX, possibly on large α‐motoneurons and on small neurons.

Reticulo‐spinal fibers of both contingents terminate on cells of all sizes, on somata as well as on dendrites.
Organization of the visual projection upon the optic tectum of a reptile (Alligator mississippiensis)
Authors: Heric Thomas M. , Kruger Lawrence
Published: January 2005

Electrical responses were recorded from the optic tectum of the alligator with steel microelectrodes, and the receptive field for each of a series of systematically spaced recording sites was delineated on a transparent plastic hemisphere positioned in front of the contralateral eye. A precise retinotopic relationship was determined with the inferior portion of the retina projecting onto the dorsal surface of the tectum, and the superior portion of the retina represented on the lateral and ventral aspects of the tectum. The equatorial line of the hemisphere is situated laterally and runs obliquely across the tectum from the rostrolateral pole to the caudomedial corner. The center of the visual field occupies a disproportionate amount of tectal space providing for functional magnification. Receptive field size and spacing diminish for the representation of the central region implying a retinal area for increased visual acuity. It is suggested that this alinearity between the visual field and the tectum is expressed in its fiber architecture and is probably a consequence of specialization of the eye rather than an evolutionary modification within the reptilian central nervous system.
Organization of the visual projection upon the optic tectum of some freshwater fish
Authors: Schwassmann Horst O. , Kruger Lawrence
Published: January 2005

In four species of freshwater fish, bass, carp, bluegill and goldfish, the topographical relations of the visual field with the contralateral optic tectum were investigated, using a small light as stimulus in the visual field and recording the electrical response of the tectum with a metal microelectrode. The results show a precisely organized visual projection onto the contralateral tectum in which the anterior visual field lies anteriorly on the tectum, the temporal field posteriorly, the dorsal field medio‐dorsally, and the ventral field in the latero‐ventral part of the tectum. The projection was found to be essentially linear and uniform with no indication of a specialized area in the visual field in those species investigated. Some receptive fields extended into the anterior binocular visual field.