bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy
Authors: Chugani Harry T. , Jacobs Bob
Published: January 2005

In 3 children who had undergone cerebral hemispherectomy (hemidecortication) between the ages of 1 year 5 months and 4 years for the alleviation of intractable epilepsy, cerebral glucose utilization was studied serially with positron emission tomography. Three to 7 months after hemispherectomy, glucose utilization in the caudate nuclei on the side of hemispherectomy had decreased to below preoperative values, presumably due to total deprivation of ipsilateral cortical input. One to 2.5 years after surgery, complete restoration of glucose metabolic activity to preoperative levels was seen in 2 patients and partial recovery was seen in 1 patient. These alterations of cerebral glucose utilization are believed to reflect microscopic anatomical reorganizational changes (e.g., collateral sprouting) that have been documented following similar lesions in several animal models. Our findings suggest that positron emission tomography may provide a sensitive measure of developmental brain plasticity in vivo.
Complex I, Iron, and ferritin in Parkinson's disease substantia nigra
Authors: Mann V. M. , Cooper J. M. , Daniel S. E. , Srai K. , Jenner P. , Marsden C. D. , Schapira A. H. V.
Published: January 2005

Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron‐ferritin ratio and complex I activity in the substantia nigra samples.
Immunological and pathological study of anti‐Ri–associated encephalopathy
Authors: Hormigo Adialia , Dalmau Josep , Rosenblum Marc K. , River Mary E. , Posner Jerome B.
Published: January 2005

A patient with high titers of the anti‐Ri antibody died 3 years after a progressive course with ataxia, opsoclonus, dementia, and peripheral neuropathy. At autopsy, no tumor was found. The nervous system exhibited severe Purkinje cell loss and contained perivascular and interstitial inflammatory infiltrates, particularly involving the brainstem. B and CD4 cells predominated in the perivascular spaces and CD8 cells in the interstitial infiltrates. Complement reactivity and natural killer cells were present and predominated in areas with more intense inflammatory infiltrates. Deposits of IgG were detected in the cytoplasm and nuclei of some neurons, particularly those in the brainstem tegmentum. The proportion of anti‐Ri IgG in the total IgG extracted from various areas of the brain, serum, and cerebrospinal fluid was determined by quantitative western blot analysis. Anti‐Ri reactivity was identified in immunoblots of all regions of the brain, but it predominated in basis pontis and dorsal mesencephalon. Our findings support the hypothesis of an autoimmune basis for the disorder and suggest that an antibody‐mediated mechanism may play a role in its pathogenesis.
Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins
Authors: Sobue Gen , Ueno‐Natsukari Ikuko , Okamoto Hideki , Connell Thomas A. , Aizawa Izumi , Mizoguchi Koichi , Honma Masamitsu , Ishikawa Gen , Mitsuma Terunori , Natsukari Naoki
Published: January 2005

We describe genetically proven monozygotic twins with the adult form of adrenoleukodystrophy with significant phenotypic heterogeneity. Myeloneuropathy was common to both patients, but cognitive impairment and affective symptoms with extensive demyelination in the brain were prominent in the older twin, while adrenal insufficiency was predominant in the younger twin. The younger twin, however, exhibited affective symptoms similar to those displayed by his elder twin 10 years later. These findings suggest that nongenetic factors are important in determining the phenotypic variation of adrenoleukodystrophy gene.
Late‐onset mitochondrial myopathy
Authors: Johnston Wendy , Karpati George , Carpenter Stirling , Arnold Douglas , Shoubridge Eric A.
Published: January 2005

In the majority of patients with mitochondrial encephalomyopathies, signs and symptoms appear in the first three decades of life. Here we report on a group of 9 older patients (>69 years old) with late‐onset skeletal myopathy characterized by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle energy status, suggestive of a primary mitochondrial disease. The clinical phenotype was somewhat variable. However, all patients shared a common feature of insidious moderate proximal muscle weakness; some also showed fatigability and axial muscle weakness. In situ hybridization analysis demonstrated accumulations of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of muscle fibers in the patient group. These fiber segments appeared as ragged red with the modified Gomori trichrome stain and hyperreactive with a modified succinate dehydrogenase stain. Most were negative for cytochrome c oxidase activity. On transverse sections their mean frequency was 0.69% (trichrome) and 1.97% (succinate dehydrogenase) significantly above control levels. Multiple mtDNA deletions were demonstrated by the polymerase chain reaction in both the patients and an age‐matched control group, but not in younger control subjects. Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a decreased phosphocreatine‐inorganic phosphate ratio in the patient group. The myopathy in this group of patients appears to result from mitochondrial dysfunction related to the clonal expansion of different mtDNA deletions in individual fiber segments. While the origin of the mtDNA mutations is not clear, the phenotype seems to represent an exaggerated form of what is observed in the normal aging process.
Circulating, soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: Correlation with clinical activity
Authors: Dore‐Duffy Paula , Newman Walter , Balabanov Roumen , Lisak Robert P. , Mainolfi Elizabeth , Rothlein Robert , Peterson Margaret
Published: January 2005

Soluble adhesion protein intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and endothelial leukocyte adhesion molecule (E‐selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with relapsing‐remitting multiple sclerosis (RRMS) in remission and in exacerbation, as well as patients with chronic progressive MS, stable MS, and in patients with other neurological and inflammatory diseases (ONDs). Serum ICAM‐1 and E‐selectin were significantly elevated in patients with MS over those with ONDs and controls. CSF VCAM‐1 and E‐selectin were found to be elevated over control and disease control samples. No increase in CSF ICAM‐1 was observed. Results were analyzed longitudinally and by MS category. In paired CSF and serum samples from patients in exacerbation, elevated VCAM‐1 correlated with increased serum VCAM‐1 in 5 of 7 patients. Elevated CSF E‐selectin did not correlate with elevations in serum E‐selectin.
Basic mechanisms of generalized absence seizures
Authors: Snead O. Carter
Published: January 2005

Generalized absence seizures are neurophysiologically, pharmacologically, and developmentally unique and comprise the primary seizure type in a number of different absence epilepsy syndromes. Over the last 10 years, the availability of a number of animal models of generalized absence seizures and of sophisticated in vitro electrophysiological techniques that allow investigation of cortical and thalamic networks has begun to shed light on the pathogenesis of this disorder. The basic underlying mechanism appears to involve thalamocortical circuitry and the generation of abnormal oscillatory rhythms from that particular neuronal network. Biochemical mechanisms operative within thalamocortical circuitry during this neuronal oscillation seem to entail phase‐locked ‐aminobutyric acid (GABA)B‐mediated inhibition alternating with glutamate‐mediated excitation. The basic cellular mechanism operative within this tension between excitation and inhibition appears to involve the T‐type calcium current. Local circuitry within the thalamus may influence these oscillatory rhythms by GABAA‐mediated inhibition. Pharmacological factors at play external to thalamocortical circuitry include cholinergic, dopaminergic, and noradrenergic mechanisms. Pathways that utilize these various neurotransmitters project onto the thalamus and/or cortex from sites distant to those structures and may modulate the process either up or down. Perturbation of one or more of these neuronal networks may lead to abnormal neuronal oscillatory rhythms within thalamocortical circuitry, with a resultant generation of bilaterally synchronous spike wave discharges that characterize generalized absence seizures. Our increasing understanding of the basic mechanisms that underlie generalized absence seizures promises to allow, for the first time, a rational design of drug treatment for a seizure disorder based on the pathogenesis of that disorder.
Outcome assessment for epilepsy surgery: The impact of measuring health‐related quality of life
Authors: Vickrey Barbara G. , Hays Ron D. , Engel Jerome , Spritzer Karen , Rogers William H. , Rausch Rebecca , Graber Jason , Brook Robert H.
Published: January 2005

Epilepsy surgery is an increasingly common treatment for intractable epilepsy; yet there is no clear consensus among experts on how to report epilepsy surgery outcome. Most published outcome reporting systems focus on seizure frequency and type but differ in how they define clinically distinct outcome categories. We used a reliable and valid measure of self‐reported health‐related quality of life (HRQOL), the Epilepsy Surgery Inventory (ESI)‐55, as an external standard by which to evaluate seven previously published, seizure‐based outcome classification systems. The ESI‐55 was administered to 133 adults who had previously undergone surgery for intractable epilepsy, and results were linked to data on their seizure occurrence before and after surgery (over the year prior to their HRQOL reports). These 133 patients were classified according to each seizure‐based outcome system, and variation in HRQOL across outcome groups was evaluated using analysis of variance. Results reveal noteworthy variation in the extent to which different systems reflect patients' HRQOL at follow‐up. We modified existing systems to derive a seizure‐based surgery outcome system that most closely reflects HRQOL when applied over the latest 1‐year postoperative interval.
Analysis of the SCAI CAG repeat in a large number of families with dominant ataxia: Clinical and molecular correlations
Authors: Dubourg O. , Dürr A. , Cancel G. , Stevanin G. , Penet C. , Agid Y. , Brice A. , Chneiweiss H.
Published: January 2005

Autosomal dominantly inherited ataxias are a clinically and genetically heterogeneous group of neurodegenerative disorders. The gene involved in one subtype, spinocerebellar ataxia 1 (SCA I), was first localized to chromosome 6p. An unstable CAG repeat has been identified as the responsible mutation. In this study, 88 families with various types of inherited ataxias and 16 individuals with sporadic cerebellar ataxia were investigated to determine the frequency of this mutation, the behavior of the SCA1 CAG repeat during transmission, and the clinical features specific to this form of disease. Only 12 of the families carried the SCA1 mutation; 10 of the 12 were of French origin. When transmitted paternally, the repeat was more unstable and larger in size. Age at onset was inversely correlated with the number of CAG repeats. Anticipation in age at onset of about 11 years was observed in offspring. Analysis of the clinical features did not distinguish SCA1 from other forms of dominantly inherited ataxias. In the absence of distinguishing clinical characteristics, the diagnosis of SCA1 in single affected patients or family members can only be made by direct detection of the mutation, opening the way for presymptomatic testing.
Cerebrospinal fluid 5‐hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus‐myoclonus syndrome
Authors: Pranzatelli M. R. , Huang Y. , Tate E. , Stanley M. , Noetzel M. J. , Gospe S. M. , Banasiak K.
Published: January 2005

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus‐myoclonus syndrome, the serotonin metabolite 5‐hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age‐ and gender‐matched control subjects by high‐pressure liquid chromatography with elecrochemical detection. 5‐Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus‐myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus‐myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5‐hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus‐myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus‐myoclonus with low cerebrospinal fluid levels of 5‐hydroxyindoleacetic acid and homovanillic acid. Biochemical heterogeneity for this clinical phenotype may have implications for responsiveness to treatment with serotonergic and other drugs.
Multiple Sclerosis: Limited Diversity of the Vδ2‐Jδ3 T‐Cell Receptor in Chronic Active Lesions
Authors: Battistini L. , Selmaj K. , Kowal C. , Ohmen J. , Modlin R. L. , Raine C. S. PHD, DSC , Brosnan C. F.
Published: January 2005

T lymphocytes bearing the γδ T‐cell receptor have been found in the central nervous system of patients with multiple sclerosis in association with demyelinated lesions. Although the biological function of these cells remains to be established, it has been proposed that they are involved in the response to highly conserved antigens, such as heat shock proteins (hsp), expressed during tissue damage and thus may contribute to the development of an autoimmune response. Using polymerase chain reaction, we probed for the presence of T‐cell receptor γδ cells in fresh‐frozen early autopsy brain tissue from patients with multiple sclerosis and patients with non‐multiple sclerosis conditions. The results demonstrated the presence of two major V‐J combinations of the T‐cell receptor δ chain–Vδ2‐Jδ3, Vδ2‐Jδ1– and we used a direct sequencing technique to determine whether this γδ T‐cell population was clonal or diverse. In chronic‐active plaques from 9 patients with multiple sclerosis, we found a striking predominant gene rearrangement within the Vδ2‐Jδ3 T‐cell receptor population that was not present in central nervous system tissue from patients with other neurological diseases. In contrast, within the Vδ2‐Jδ1 T‐cell receptor population, a predominant rearrangement pattern was detected in only 1 of the multiple sclerosis patients. The sequence of the predominant Vδ2‐Jδ3 gene rearrangement was confirmed by cloning and sequencing the gene products from 1 multiple sclerosis patient. This junctional region was characterized by shortened Dδ and Jδ segments, few N region insertions, and use of the third reading frame of the Dδ3 segment. These data strongly support the conclusion that within chronic‐active multiple sclerosis lesions, T cells bearing the Vδ2‐Dδ3‐Jδ3 receptor might have arisen as a response to a common antigen.
Huntington's disease gene: Regional and cellular expression in brain of normal and affected individuals
Authors: Landwehrmeyer G. Bernhard , McNeil Sandra M. , Dure Leon S. , Ge Pei , Aizawa Hitoshi , Huang Qin , Ambrose Christine M. , Duyao Mabel P. , Bird Edward D. , Bonilla Ernesto , de Young Margot , Avila‐Gonzales Alejandro J. , Wexler Nancy S. , DiFiglia Marian , Gusella James F. , MacDonald Marcy E. , Penney John B. , Young Anne B. , Vonsattel Jean‐Paul
Published: January 2005

Huntington's disease (HD) is an autosomal dominant disorder characterized by involuntary movements, dementia, and progressive, global, but regionally accentuated, brain atrophy. The disease affects the striatum most severely. An expansion of a trinucleotide repeat on chromosome 4p16.3 within the coding region of a gene termed IT15 has been identified as the mutation causing HD. The normal function of IT15 and the mechanisms by which the presence of the mutation cause HD are unknown. Although IT15 expression has been detected in the brain, as well as in other organ tissues, by Northern blot and in situ hybridization, it is not known whether a preferential regional or cellular expression of IT15 exists within the central nervous system of normal, affected, and presymptomatic individuals. Using quantitative in situ hybridization methods, we examined extensively the regional and cellular expression of IT15. In controls, IT15 expression was observed in all brain regions examined with the highest levels seen in cerebellum, hippocampus, cerebral cortex, substantia nigra pars compacta, and pontine nuclei. Expression in the striatum was intermediate and expression in the globus pallidus was low. IT15 was expressed predominantly in neurons; a low but significant level of expression was seen in glial cells. Analysis of grain counts per square micrometer in neurons showed that the regional differences in the level of mRNA expression were related to density and size of neurons in a given region and not primarily to differences in levels of mRNA expression in individual cells after correction for cell size. Neurons susceptible to degeneration in HD did not selectively express high levels of IT15 mRNA. In HD brains (grades 2–4), the distribution and levels of IT15 mRNA were comparable with controls in all areas except in neostriatum where the intensity of labeling was significantly reduced. Presymptomatic HD brains had a striatal expression similar to controls and surviving striatal neurons in more advanced HD had an expression of IT15 within normal limits. It is apparent from these results that the presence of expanded trinucleotide repeats in HD does not result in the absence of IT15 mRNA expression or in altered patterns or levels of expression. The lack of correlation between the levels of IT15 mRNA expression and susceptibility to degeneration in HD strongly suggests that the mutant gene acts in concert with other factors to cause the distinctive pattern of neurodegeneration in HD.
Serum anti‐GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome
Authors: Jacobs Bart C. , Endtz Hubert PH. , van der Meché Frans G. A. , Hazenberg Maarten P. , Achtereekte Herbert A. M. , van Doorn Pieter A.
Published: January 2005

Three patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti‐GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme‐linked immunosorbent assay and thin‐layer chromatography overlay. In enzyme‐linked immunosorbent assay inhibition studies the anti‐GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome–associated C. jejuni strains. The presence of anti‐GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti‐GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross‐reactivity of anti‐GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome–associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.
Molecular and clinical findings in a family with dentatorubral‐pallidoluysian atrophy
Authors: Potter Nicholas T. , Meyer Michael A. , Zimmerman Andrew W. , Eisenstadt Michael L. , Anderson Ilse J.
Published: January 2005

Herein we describe the molecular and clinical findings in a North American Caucasian family with dentatorubral‐pallidoluysian atrophy (DRPLA). These patients all presented with an autosomal dominant neurodegenerative disorder characterized by a variable combination of clinical symptoms including seizures, ataxia, dementia, choreiform movements, mental retardation, and psychiatric disease. Neuroradiologic findings in the index case revealed deep subcortical white matter changes on magnetic resonance imaging. Prior to referral, the family carried a diagnosis of Huntington's disease (HD). Subsequent direct molecular testing for HD failed to identify the HD expansion mutation in affected individuals. Molecular testing for DRPLA, however, demonstrated the presence of the recently characterized DRPLA expansion mutation in all affected individuals. The size of the expansion correlated with the age of onset of clinical symptoms. As DRPLA has rarely been reported in North American and European populations, the molecular confirmation of DRPLA in this family provides support for the hypothesis that DRPLA may not be as geographically restricted as once thought.
Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children
Authors: van der Knaap M. S. , Barth P. G. , Stroink H. , van Nieuwenhuizen O. , Arts W. F. M. , Hoogenraad F. , Valk J.
Published: January 2005

An identical syndrome of cerebral leukoencephalopathy and megalencephaly with infantile onset was discovered in 8 children, including 2 siblings. Neurological findings were initially normal or near normal, despite megalencephaly and magnetic resonance imaging (MRI) evidence of severe white matter affection. Slowly progressive ataxia and spasticity developed, while intellectual functioning was preserved for years after onset of the disorder. MRI characteristics included diffuse abnormality in signal intensity and swelling of the cerebral hemispheral white matter with cyst‐like spaces in the frontoparietal and anterior‐temporal subcortical areas. MR spectra were relatively mildly abnormal. Screening for inborn errors, especially those that cause either megalencephaly or white matter disease or both was negative. A distinguishing feature of the present disorder is the apparently severe abnormality of the cerebral white matter as demonstrated by MRI, which contrasts with the remarkably slow course of functional deterioration.
A new mitochondrial DNA mutation associated with progressive dementia and chorea: A clinical, pathological, and molecular genetic study
Authors: Nelson I. , Hanna M. G. , Alsanjari N. , Scaravilli F. , Morgan‐Hughes J. A. , Harding A. E.
Published: January 2005

A novel mitochondrial DNA transfer RNA mutation at position 5549 was identified in a patient with dementia, chorea, cerebellar ataxia, deafness, and peripheral neuropathy in the absence of clinical myopathy. Muscle biopsy specimens showed ragged red and cytochrome oxidase‐negative fibers, and reduced complex I activity on polarography. There was diffuse neuronal loss and gliosis throughout the brain on postmortem examination. The heteroplasmic mutation had a widespread distribution in autopsy tissues.
Antibodies against GM1 ganglioside affect K+ and NA+ currents in isolated rat myelinated nerve fibers
Authors: Takigawa Tomoko , Yasuda Hitoshi , Kikkawa Ryuichi , Shigeta Yukio , Saida Takahiko , Kitasato Hiroshi
Published: January 2005

High titers of anti‐GM1 ganglioside antibodies (anti‐GM1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti‐GM1 antibody using the petroleum jelly–gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti‐GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti‐GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited by step depolarization, with little effect on Na+ current. In the presence of active complement, however, anti‐GM1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement‐supplemented antisera from which anti‐GM1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti‐GM1 antibodies themselves can uncover K+ channels in the paranodal region, while anti‐GM1 antibodies bound to the nodal membrane in the presence of complement may form antibody‐complement complexes that block Na+ channels and disrupt the membrane at the node of Ranvier.
Deficits of smooth‐pursuit eye movement after unilateral frontal lobe lesions
Authors: Morrow Mark J. , Sharpe James A.
Published: January 2005

We recorded horizontal smooth‐pursuit responses to sinusoidal and step‐ramp stimuli in 7 patients with unilateral frontal lobe lesions. Five patients had directional smooth‐pursuit deficits, all with impairment toward the side of cerebral damage. Ipsidirectional pursuit defects involved pursuit maintenance to sinusoidal targets, pursuit initiation to step‐ramp targets, or both. No patient had asymmetry of smooth pursuit according to the retinal hemifield of target appearance. Smooth‐pursuit velocities were subnormal in both horizontal directions in 4 patients. The human frontal lobes participate in the initiation and maintenance of smooth pursuit in both directions, with a greater ipsilateral contribution. Of 5 patients with ipsilateral pursuit impairment, 3 had cerebral lesions in the area of the frontal eye field (FEF). These 3 patients also made inaccurate saccades to targets moving away from the side of the lesion, implying that the FEF transmits motion information to the saccadic system. Two patients with ipsidirectional smooth‐pursuit defects had cerebral damage that spared the FEF, indicating that other frontal regions also contribute to smooth pursuit.
Effects of brain‐derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease
Authors: Ikeda Ken , Klinkosz Bogdan , Greene Tom , Cedarbaum Jesse M. , Wong Vivien , Lindsay Ronald M. , Mitsumoto Hiroshi
Published: January 2005

Brain‐derived neurotrophic factor (BDNF) has been shown to promote the survival of developing motor neurons in vitro and to rescue motor neurons from axotomy‐induced cell death in vivo. In this study, we examined the effects of exogenous BDNF on the progression of wobbler mouse motor neuron disease (MND). After clinical diagnosis at age 3 to 4 weeks, 20 affected mice received subcutaneous injections of recombinant human BDNF (5 mg/kg, n = 10) or vehicle (n = 10), three times a week for 4 weeks. In a separate experiment done to conduct a histometric analysis of the C‐5 and C‐6 ventral roots and to determine the number of myelinated nerve fibers, 7 wobbler mice received identical BDNF treatment. In the 10 BDNF‐treated wobbler mice, grip strength declined at a slower rate (p < 0.03) and was twice as great as that of vehicle‐treated animals at the end of treatment (p < 0.01). In vivo biceps (p < 0.01‐) and in vitro muscle twitch tensions (p < 0.02) were also greater than those of vehicle‐treated mice. The biceps muscle weight was 20% greater (p < 0.05) and the mean muscle fiber diameter was significantly larger in BDNF‐treated mice (p < 0.001) because the number of small (denervated) muscle fibers was markedly reduced. The number of myelinated motor axons at the cervical ventral roots studied in the additional 7 affected mice was 25% greater with BDNF treatment (p < 0.0001). This study establishes that exogenous BDNF administration can retard motor dysfunction in a natural MND and diminish denervation muscle atrophy and motor axon loss.
Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain
Authors: Seeck M. , Schomer D. , Mainwaring N. , Ives J. , Dubuisson D. , Blume H. , Cosgrove R. , Ransil B. J. , Mesulam M.‐M.
Published: January 2005

Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task‐related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding. In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set.
Decreased CD3‐mediated interferon‐γ production in relapsing‐remitting multiple sclerosis
Authors: Brod Staley A. , Khan Mohammed , Bright John , Sriram Subramaniam , Marshall Gailen D. , Henninger Evelyn M. , Kerman Ronald H. , Wolinsky Jerry S.
Published: January 2005

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that has been postulated to be T‐cell mediated. We examined the proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 (anti‐CD3) monoclonal antibody concanavalin A, or ionomycin plus myristic acid palmityl ester in subjects with stable relapsing‐remitting MS. Control subjects demonstrated good proliferation to anti‐CD3 monoclonal antibody whereas subjects with relapsing‐remitting MS showed a significantly decreased anti‐CD3 monoclonal antibody‐mediated response. There was no difference in concanavalin or ionomycin plus myristic acid palmityl ester stimulation between control subjects and MS subjects. Secretion of interferon‐γ was significantly decreased and transforming growth factor‐β was significantly increased from cultures stimulated with anti‐CD3 monoclonal antibody, but not ionomycin plus myristic acid palmityl ester or concanavalin A, in MS patients compared to control subjects. Secretion of interleukin‐10 and tumor necrosis factor‐β was not different between control subjects and MS patients following stimulation with anti‐CD3 monoclonal antibody, concanavalin A, or ionomycin plus myristic acid palmityl ester, or of interleukin‐2 and interleukin‐4 following stimulation with anti‐CD3 monoclonal antibody or concanavalin A. An abnormality of signal transduction and secretion of the immunomodulatory molecule interferon‐γ may exist in MS via the CD3 T‐cell receptor complex.
Locomotor capacity of spinal cord in paraplegic patients
Authors: Dietz V. , Colombo G. , Jensen L. , Baumgartner L.
Published: January 2005

The induction of complex bilateral leg muscle activation combined with coordinated stepping movements is demonstrated in patients with complete paraplegia. This was achieved by partially unloading patients who were on a moving treadmill. In comparison to healthy subjects, the paraplegic patients displayed a less dynamic mode of muscle activation. In all other respects leg muscle electromyographic activity was modulated in a similar manner to that in healthy subjects. However, the level of electromyographic activity in the gastrocnemius (the main antigravity muscle during gait) was considerably lower in the patients. During the course of a daily locomotor training program, the amplitude of gastrocnemius electromyographic activity increased significantly during the stance phase, while inappropriate tibialis anterior activation decreased. Incompletely paraplegic patients benefited form the training with respect to performance of unsupported stepping movements on solid ground. In about half of completely paraplegic patients with low muscle tone, no beneficial effect of the training was seen. This may be due to an inhibitory effect on spinal neuronal activity by drugs patients were taking (e.g., prazosin, clonidine, cannabinoids). In this study intrathecal application of clonidine drastically reduced, while epinephrine enhanced locomotor muscle electromyographic activity. The results of this study promise to be significant in the treatment of paraplegic patients.
Outcome after spinal reirradiation for malignant epidural spinal cord compression
Authors: Schiff David , Shaw Edward G. , Cascino Terrence L.
Published: January 2005

Radiotherapy is effective for most case of spinal cord compression. Although recurrent spinal cord compression is a common problem, little is known about whether reirradiation preserves neurologic function and what risk of radiation myelopathy it carries. To investigate this question, we reviewed patients at the Mayo Clinic between 1975 and 1992 undergoing two or more courses of radiotherapy to the same segment of the spinal column with radiographically documented epidural disease at the time of reirradiation to determine outcome as measured by the ability to walk and by survival. Fifty‐four patients met the study criteria. Radiation doses for the first course ranged from 2,250 to 5,400 cGy (median, 3,000 cGy), and total dose for all courses to the reirradiated spinal segment ranged from 3,650 to 8,089 cGy (median, 5,425 cGy). All patients were ambulatory following the first course of radiation, 40 (74%) were ambulatory at the onset of reirradiation, and 42 (78%) were ambulatory at the end of reirradiation. Thirty‐seven patients (69%) remained ambulatory at their last follow‐up 6 days to 80 months following reirradiation (median, 4.7 months). Five patients eventually became nonambulatory 6.5 to 35 months following reirradiation. Median survival for all patients following reirradiation was 4.2 months. We conclude that for cancer patients with progressive epidural disease following radiotherapy, reirradiation frequently preserves ambulation and carries minimal risk of radiation myelopathy during the patients' lifetime.
Gene dose of the ε4 allele of apolipoprotein E and disease progression in sporadic late‐onset alzheimer's disease
Authors: Frisoni Giovanni B. , Govoni Stefano , Geroldi Cristina , Bianchetti Angelo , Calabresi Laura , Franceschini Guido , Trabucchi Marco
Published: January 2005

A strong association has been described in cross‐sectional studies between the ε4 allele of the apolipoprotein E and late‐onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the ε4 allele in 62 sporadic LOAD (onset at age 70 and over) patients. Disease progression was estimated retrospectively with the Mini‐Mental State Examination (MMSE) amounting to 4.7, 3.8, and 2.2 points per year (sex‐adjusted test for trend: p = 0.01) and with the Clinical Dementia Rating (CDR) to 0.76, 0.67, and 0.42 units per year (p = 0.03) in ‐/‐, ε4/‐, and ε4/ε4 patients. The proportion of patients with fast progression decreased (p ≤ 0.005) and with slow progression increased (p = 0.002) with increasing ε4 gene dose. These findings were confirmed in a smaller sample of 28 patients for whom longitudinal assessments of MMSE were available and when nonlinear progression of the disease was accounted for in a stratified analysis. These data suggest that disease duration might be longer in ε4 carriers and that this might at least partly account for the cross‐sectional association between the ε4 allele and LOAD.
First seizures associated with playing electronic screen games: A community‐based study in Great Britain
Authors: Quirk J. A. , Fish D. R. , Smith S. J. M. , Sander J. W. A. S. , Shorvon S. D. , Allen P. J.
Published: January 2005

Active surveillance by virtually all electroencephalographic departments throughout Great Britain identified 118 patients who had a first seizure while playing an electronic screen game during two 3‐month periods. Patients were divided into Group A (46 patients)—those for whom there was thought to be a definite causal relationship (type 4 photoparoxysmal response); Group B (25 patients)—those for whom there was a probable causal relationship (types 1–3 photoparoxysmal response, clinical evidence of photosensitivity, subsequent recurrent seizures on repeat exposure to electronic screen games, and/or occipital spikes in the resting electroencephalogram); and Group C (47 patients)—those for whom there was no apparent causal relationship. The number of patients in Group C did not exceed that expected by the chance occurrence of two common events (playing electronic screen games and incidence of epilepsy). Most (103/118) of the patients were in the age range of 7 to 19 years. Within this age group the annual incidence of first seizures triggered by playing electronic screen games (Groups A and B combined) was estimated to be 1.5/100,000.
Pallidotomy increases activity of motor association cortex in parkinson's disease: A positron emission tomographic study
Authors: Grafton Scott T. , Waters Cheryl , Sutton James , Lew Mark F. , Couldwell William
Published: January 2005

Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical‐basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement‐related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement‐related activity in motor association areas.
Movement‐related cortical potentials preceding repetitive and random‐choice hand movements in parkinson's disease
Authors: Touge T. , Werhahn K. J. , Rothwell J. C. , Marsden C. D.
Published: January 2005

The movement‐related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age‐matched control subjects. Two types of self‐paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random‐choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement‐related cortical potential was larger prior to random‐choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self‐selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.
Oculomotor function in amyotrophic lateral sclerosis: Evidence for frontal impairment
Authors: Shaunak S. , Orrell R. W. , O'Sullivan E. , Hawken M. B. , Lane R. J. M. , Henderson L. , Kennard C.
Published: January 2005

Saccadic eye movements, fixation, and smooth pursuit were recorded in 17 subjects with amyotrophic lateral sclerosis (ALS) and 11 age‐matched controls using a magnetic scleral search coil. Reflexive, remembered and antisaccades, and smooth pursuit at four target velocities were studied. Subjects with ALS showed significantly elevated error rates (distractibility) and latency in the antisaccade and remembered saccade paradigms but no abnormality of reflexive saccades. The frequency of small saccades that intruded on steady fixation (square‐wave jerks) was also increased in ALS subjects. Peak velocity gain of smooth pursuit and performance on the Wisconsin Card Sort Test did not differ significantly between the two groups. These findings are consistent with prefrontal dysfunction in ALS and provide an independent source of support for the thesis that the pathology of this condition invades frontal cortex.
Treatment of dural sinus thrombosis using selective catheterization and urokinase
Authors: Horowitz Michael , Purdy Phillip , Unwin Hal , Carstens George , Greenlee Ralph , Hise Joe , Kopitnik Tom , Batjer Hunt , Rollins Nancy , Samson Duke
Published: January 2005

Thrombosis of the cerebral dural venous sinuses, cortical draining veins, and deep cerebral veins is a rare clinical finding. Because of its low incidence and multiple etiologies, the optimum therapy for this condition will only be elucidated by a multicenter, randomized prospective study. At our institution, we favor early and aggressive management of cerebral venous sinus thrombosis with transfemoral, venous intradural infusions of the fibrinolytic agent urokinase. To date, treatment of only 13 patients using this technique has been reported in the English literature. This report adds 12 more such treated patients. Despite the presence of preinfusion infarcts in 5 patients, four of which were hemorrhagic, we incurred no major therapeutic morbidity. Functional sinus patency was achieved in 11 of 12 patients, with our only true failure occurring in an individual with symptoms of at least 2 months' duration. Good to excellent clinical outcome was achieved in 10 of 11 patients (one newborn had inadequate follow‐up).
Hu antigens: Reactivity with hu antibodies, tumor expression, and major immunogenic sites
Authors: Manley Geoffrey T. , Smitt Peter Sillevis , Dalmau Josep , Posner Jerome B.
Published: January 2005

HuD, a human neuronal RNA‐binding protein, was the first identified member of a family of antigens that also includes HuC and Hel‐N1 (Hu antigens). The serum of all patients with anti‐Hu–associated paraneoplastic encephalomyelitis and sensory neuronopathy react with HuD and Hel‐N1, but the reactivity with HuC is unknown. In the current study we examined (1) the reactivity of anti‐Hu sera with HuD, HuC, and Hel‐N1; (2) the expression of HuD, HuC, and Hel‐N1 messenger RNA in small‐cell lung cancer of patients with and those without paraneoplastic encephalomyelitis/sensory neuronopathy; (3) the correlation between anti‐Hu serum reactivity with these three Hu antigens and the type of neurological symptoms; and (4) the major immunogenic sites of HuD. Our findings indicate that all anti‐Hu sera react with HuD, HuC, and Hel‐N1. However, only HuD is expressed in the small‐cell lung cancer tumors, indicating that among the three Hu antigens, HuD appears to play a central role in triggering the anti‐Hu immune response. No differences were identified regarding the reactivity of the anti‐Hu antibodies with HuD, HuC, and Hel‐N1 and the spectrum of neurological symptoms presented by the patients. Study of the major immunogenic sites of HuD resulted in the identification of two major immunodominant regions with at least two distinct epitopes recognized by the serum of all patients with anti‐Hu—associated paraneoplastic encephalomyelitis/sensory neuronopathy.
Recurrent stroke and thrombo‐occlusive events in the antiphospholipid syndrome
Authors: Levine Steven R. , Brey Robin L. , Sawaya Kara L. , Salowich‐Palm Leeza , Kokkinos James , Kostrzema Beata , Perry Mary , Havstad Suzanne , Carey John
Published: January 2005

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7‐year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false‐positive Veneral Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo‐occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow‐up during a mean prospective follow‐up of 3 years. Over one‐half of the cohort had at least one recurrent thrombo‐occlusive event during follow‐up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo‐occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.
Why do DNA testing? Practical and ethical implications of new neurogenetic tests
Authors: Bird Thomas D. , Bennett Robin L.
Published: January 2005

Direct DNA tests for mutations in neurogenetic disorders are establishing a new era in diagnostic neurology. These highly accurate and specific tests will greatly improve diagnosis and genetic counseling, lead to more accurate assessment of prognosis, and reduce the cost of diagnostic evaluations. However, the use and interpretation of the tests can be complicated, and there are numerous social, psychological, and ethical implications of the testing that need to be recognized and anticipated. To provide the best care for our patients, neurologists need to understand the benefits and risks of this testing and properly apply it in the context of each individual clinical situation.