bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative morphological analysis of striatal cholinergic neurons in perinatal asphyxia
Authors: Burke Robert E. , Karanas Andrew L. 
Published: January 2005

AbstractAlthough the static encaphalopathies of childhood are common, little is known of the underlying alterations in the neurochemical anatomy of the brain. Using quantitative morphological techniques, we examined the effect of perinatal hypoxia‐ischemia on the number and distribution of cholinergic (ACh) neurons in a unilateral experimental striatal lesion in rats. The striatal pathology simulates status marmoratus, a recognized correlate of human dystonic cerebral palsy. We found that striatal injury results in a mean 22% decrease in the number of ACh neurons at the age of 3 to 4 weeks. The loss of neurons was relatively less than the volume loss, resulting in a mean 16% increase in neuron density. This effect was not uniform throughout the striatum; it was more pronounced caudally, resulting in a mean 52% increase in density in the most caudal striatal plane. These changes in immature rats were also seen in adult rats, indicating that there were lasting alterations in striatal cholinergic morphology. Hypoxic‐ischemic injury to the striatum also resulted in a persistent decrease in the mean area of ACh neurons. The increased density of these neurons may imply that they are relatively resistant to hypoxic‐ischemic injury. These findings may be relevant to the observation that anticholinergic drugs are among the most effective for treating dystonias, including those observed in staticencephalopathies.
Regional cerebral blood flow during focal seizures of temporal and frontocentral onset
Authors: Stefan H. , Bauer J. , Feistel H. , Schulemann H. , Neubauer U. , Wenzel B. , Wolf F. , Neundörfer B. , Huk W.‐J. 
Published: January 2005

AbstractIctal single photon emission computed tomography recordings were performed in 9 patients in the course of 11 seizures. Injections of radionuclide were made an average of 72 seconds after the onset of the seizure as indicated by electroencephalography. All patients also underwent interictal recordings. In 6 patients, the localization of the electroencephalographic focus and the morphological lesions corresponded with the ictal hyperperfusion. This could be seen in single photon emission computed tomography. Seizures triggered by hyperventilation, and seizures of patients with anatomical brain lesions (e.g., cysts, surgical defects, and recent injections of technetium‐hexamethylene‐propyleneamine‐oxime) showed an absent or noncorresponding localization of the ictal recording. The ictal and interictal recording seems suitable as a confirmatory noninvasive method for the localization of the epileptogenic focus, particularly in the preoperative evaluation of epilepsy.
Orally administered 4‐aminopyridine improves clinical signs in multiple sclerosis
Authors: Davis Floyd A. , Stefoski Dusan , Rush Jean 
Published: January 2005

Abstract4‐Aminopyridine (4‐AP), a potassium channel blocker, restores conduction in blocked, demyelinated animal nerve. Its administration to multiple sclerosis (MS) patients produces transient neurological improvements. Vision improves after either oral or intravenous administration, whereas motor function improvement has been reported only with the latter. To assess further its potential as a practical symptomatic treatment, we studied the efficacy of single, oral doses of 4‐AP on both visual and motor signs in MS. Twenty temperature‐sensitive male MS patients were given either 10 to 25 mg of 4‐AP or identically appearing lactose placebo capsules. Static quantitative perimetry, critical flicker‐fusion, visual acuity, visual evoked potentials, and videotaped neurological examinations were monitored. All of 15 MS patients given 4‐AP mildly to markedly improved. Motor functions (power, coordination, gait) improved in 9 of 13 involved, vision in 11 of 13, and oculomotor functions in 1 of 2. Improvements developed gradually at doses as low as 10 mg, usually beginning within 60 minutes after drug administration, and reversed gradually over 4 to 7 hours. No serious adverse effects occurred. No significant changes were observed in 5 MS patients given placebo. We conclude that orally administered 4‐AP produces clinically important improvements in multiple, chronic deficits in MS. Further studies are warranted to assess efficacy and safety of prolonged administration.
Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment
Authors: Chugani Harry T. , Shields W. Donald , Shewmon D. Alan , Olson Donald M. , Phelps Michael E. , Peacock Warwick J. 
Published: January 2005

AbstractPositron emission tomography (PET) of local cerebral glucose metabolism in 13 children with infantile spasms of undetermined cause (cryptogenic spasms) revealed unilateral hypometabolism involving the parieto‐occipito‐temporal region in 5 female infants. Cranial computed tomography showed normal findings in all infants. Magnetic resonance imaging (MRI) demonstrated a normal appearance in 4 of the 5 infants; in 1 infant, MRI revealed a subtle abnormality consisting of poor demarcation between occipital gray and white matter. Surface electroencephalography (EEG) in 4 showed hypsarrythmia at some time in the patients' courses, but at other times showed localized or lateralized abnormalities corresponding to areas of PET‐detected hypometabolism. Because of poor seizure control, 4 infants underwent surgical removal of the cortical focus guided by intraoperative electrocorticography and were seizure free postoperatively. Neuropathological examination of resected tissue in each showed microscopic cortical dysplasia. Our findings indicate that in infants with cryptogenic spasms, PET can effectively identify those due to unsuspected focal cortical dysplasia, for which resective surgery offers improved prognosis.
Tourette's syndrome: A neurochemical analysis of postmortem cortical brain tissue
Authors: Singer Harvey S. , Hahn In‐Hei , Krowiak Edward , Nelson Eric , Moran Timothy 
Published: January 2005

AbstractPostmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS‐affected brains, the concentration of adenosine 3′,5′ ‐monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter‐synthesizing enzymes choline acetltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5‐hydroxyindoleacetic acid were not altered. Postsynaptic receptor‐binding activity for muscarinic cholinergic ([3H] quinuclidiny1 benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system.
Instability of gaze during locomotion in patients with deficient vestibular function
Authors: Grossman Gerald E. , Leigh R. John 
Published: January 2005

AbstractWe measured the stability of gaze in the horizontal and vertical planes, in 2 patients with bilaterally deficient vestibular function while they sat, stood still, walked in place, and made active horizontal and vertical head rotations. During sitting and standing, gaze was equally as stable as that in normal subjects. During walking in place, however, gaze velocity was double that of normal subjects. Thus, our patients' complaints of impaired vision and oscillopsia during walking could be ascribed to excessive motion of images on their retinas. Eye movements compensated for head rotations more effectively (higher gain) during active head rotations than during locomotion; this difference may be due to the predictable nature of active head movements. We conclude that testing of patients with vestibular symptoms should include stimuli corresponding to the rotational head perturbations that occur during locomotion; such head rotations have nonpredictable characteristics and a frequency range of 0.5 to 5.0 Hz.
An unusual variant of Becker muscular dystrophy
Authors: De Visser Marianne , Bakker Egbert , Defesche Joep C. , Bolhuis Piet A. , Van Ommen Gert Jan 
Published: January 2005

AbstractWe report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed vacuoles. DNA analysis revealed a deletion in the dystrophin gene, establishing a diagnosis of Becker muscular dystrophy. Both the absence of calf hypertrophy and the presence of rimmed vacuoles are unusual features in this disorder.
CGS‐19755, A competitive NMDA receptor antagonist, reduces calcium‐calmodulin binding and improves outcome after global cerebral ischemia
Authors: Grotta J. C. , Picone C. M. , Ostrow P. T. , Strong R. A. , Earls R. M. , Yao L. P. , Rhoades H. M. , Dedman J. R. 
Published: January 2005

AbstractWe evaluated several doses of cis‐4‐(phosphonomethyl)‐2‐piperidine‐carboxylic acid (CGS‐19755), a potent competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist, systemically administered either before or after 20 to 30 minutes of global ischemia in rats. We measured outcome by mortality, histological damage by light microscopy, and learning ability on an eight‐arm maze, and determined the drug's mechanism of action by an immunohistochemical assay of calcium‐calmodulin binding. High‐dose treatment begun prior to ischemia resulted in reduced cellular damage in severely ischemic hippocampal tissue, but also caused high mortality due to respiratory depression. Treatment begun 30 minutes after ischemia resulted in little histological protection but significantly improved learning ability when tested 1 month after ischemia, and did not increase mortality. Furthermore, CGS‐19755, 10 mg/kg intraperitoneally, begun either before or after ischemia substantially reduced calcium influx into ischemic neurons as evidenced by reduced calcium‐calmodulin binding. We conclude that CGS‐19755 prevents calcium entry into ischemic neurons and may be effective therapy for very acute cerebral ischemia.
Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine
Authors: Eleff S. M. , Barker P. B. , Blackband S. J. , Chatham J. C. , Lutz N. W. , Johns D. R. , Bryan R. N. , Hurko O. 
Published: January 2005

AbstractThe hypothesis that brain mitochondria are directly affected in several phenotypes associated with disordered oxidative phosphorylation was tested using phosphorus 31 (31P) magnetic resonance spectroscopy. Abnormal phosphorylation potentials in skeletal muscle have been demonstrated by 31P magnetic resonance spectroscopy in patients with mitochondrial cytopathies (heritable disorders of oxidative phosphorylation), but abnormalities of phosphorylation potentials in other organs have not been documented. Several lines of evidence suggest that these mutations may affect mitochondria in nonmuscle tissue. In this study we found that phosphocreatine‐to‐ATP ratios in brain were significantly reduced and that calculated brain ADP concentrations, phosphorylation potentials, and percentage of maximal rate of ATP synthesis were significantly altered in the 5 patients examined. This study indicates a primary abnormality of mitochondrial function in the brain, even in the absence of clinically evident cerebral dysfunction.
The short‐duration response to apomorphine: Implications for the mechanism of dopaminergic effects in parkinsonism
Authors: Gancher Stephen T. , Woodward William R. , Gliessman Perry , Boucher Brian , Nutt John G. 
Published: January 2005

AbstractThe pharmacological basis of the short‐duration response to dopaminergic stimulation in parkinsonism is not completely understood. Whereas it is generally assumed that the response reflects concurrent dopamine receptor occupancy, it is also possible that receptor activation triggers events that outlast the time that receptors are occupied by agonist. To distinguish between these two possibilities, we administered apomorphine, a mixed D1‐D2 agonist with rapid equilibration between plasma and brain, to patients with parkinsonism. The clinical response to apomorphine injections lagged behind peak plasma concentrations and persisted beyond the time plasma apomorphine concentrations fell below threshold levels, which were estimated from peak plasma apomorphine concentrations following ineffective doses. We conclude that dopaminergic stimulation triggers effects that outlast the period of receptor occupancy by agonist. Understanding these steps may offer new pharmacological therapies for parkinsonism.
Soluble interleukin‐2 receptors in cerebrospinal fluid from individuals with various neurological disorders
Authors: Kittur Smita D. , Kittur Dilip S. , Soncrant Timothy T. , Rapoport Stanley I. , Tourtellotte Wallace W. , Nagel James E. , Adler William H. 
Published: January 2005

AbstractSoluble interleukin‐2 receptor (IL‐2R) levels in the cerebrospinal fluid (CSF) were studied in infectious, inflammatory, degenerative, and neoplastic disorders to evaluate their usefulness as a marker for the presence of activated T cells, thus indicating an inflammatory process. CSF from control subjects and patients with stationary, progressive, and treated multiple sclerosis (MS); aseptic meningitis; lymphoid and nonlymphoid central nervous system (CNS) tumors; Alzheimer's disease, as well as serum from MS patients and control subjects were studied for levels of soluble IL‐2R. A significant increase in CSF IL‐2R levels was observed in patients with MS, meningitis, and lymphoid CNS tumors; the MS group showed the highest values. CSF from individuals with Alzheimer's disease and from patients with nonlymphoid tumors did not show significantly elevated values. Serum IL‐2R levels were significantly higher in MS patients than in control subjects, but there was no significant correlation between individual serum and CSF IL‐2R levels. This study suggests the presence of activated T‐lymphocytes in the CNS of patients with MS.
Anoxic injury of mammalian central white matter: Decreased susceptibility in myelin‐deficient optic nerve
Authors: Waxman Stephen G. , Davis Peter K. , Black Joel A. , Ransom Bruce R. 
Published: January 2005

AbstractThe rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia‐induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin‐deficient (md) strain of rat. Acutely isolated optic nerves from 19‐ to 21‐day‐old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37T, and exposed to a standard 60‐minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action poten‐ tial, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 ± 25%) than did control optic nerves (33 ± 21%; p < 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter.
IgM deposits at nodes of ranvier in a patient with amyotrophic lateral sclerosis, anti‐GM1 antibodies, and multifocal motor conduction block
Authors: Santoro Maria , Thomas Florian P. , Fink Matthew E. , Lange Dale J. , Uncini Antonino , Wadia Noshir H. , Latov Norman , Hays Arthur P. 
Published: January 2005

AbstractWe studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti‐GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath. When injected into rat sciatic nerve, the serum IgM bound to the nodes of Ranvier, and the binding activity was removed by preincubation with GM1. These observations suggest that anti‐GM1 antibodies may have caused motor dysfunction by binding to the nodal and paranodal regions of peripheral nerve.
Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection
Authors: Brew Bruce J. , Bhalla Ravi B. , Paul Morris , Gallardo H. , McArthur Justin C. , Schwartz Morton K. , Price Richard W. 
Published: January 2005

AbstractWe evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood‐brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease‐specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.
Aggravation of myasthenia gravis by erythromycin
Authors: May Eugene F. , Calvert Preston C. 
Published: January 2005

AbstractErythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction.
Familial Creutzfeldt‐Jakob disease without periodic EEG activity
Authors: Tietjen Gretchen E. , Drury Ivo 
Published: January 2005

AbstractFour members of a kindred with Creutzfeldt‐Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt‐Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt‐Jakob disease, as it is in other slow transmissible encephalopathies.
Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti‐neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration
Authors: Sakai Koichiro , Mitchell Dennis J. , Tsukamoto Tetsuro , Steinman Lawrence 
Published: January 2005

AbstractWe isolated a complementary DNA clone encoding a 52‐kd protein recognized by an antineuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti‐neuronal cell antibody from the patient, and its molecular weight was identical to that of antigenic proteins in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydrophilic residues, the calculated relative molecular mass was 51,238, and the predicted value of the isoelectric point was 4.99. This complementary DNA sequence and the deduced protein sequence have not been reported previously, and the sequences showed no homologies with the complimentary DNA or the amino acid sequences in the GenBank, EMBL, or NBRF databases, including the complementary DNA for a 34‐kd cerebellar protein (CDR34) that is recognized by an anti‐Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue, the intestine.
Normal proprioceptive trigeminal afferents in patients with Sjögren's syndrome and sensory neuronopathy
Authors: Valls‐Sole Josep , Graus Francesc , Font Josep , Pou Adolf , Tolosa Eduard S. 
Published: January 2005

AbstractA pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described in patients with Sjögren's syndrome. Conventional electromyographic (EMG) studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion. Noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei, respectively, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigeminal reflexes in 5 patients with Sjögren's syndrome and pure sensory neuropathy, in 10 patients with sensory‐motor neuropathies of other causes, and in 10 healthy subjects. Our results show that patients with Sjögren's syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal, cutaneous‐induced masseter silent period had normal jaw jerks, whereas patients with sensory‐motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks. These findings suggest that the lesion in pure sensory neuropathy involves damage to the neurons of the gasserian ganglia and not to the trigeminal axons, since an axonal lesion would be expected to involve the large axons from muscle spindle receptors.
Striatal function in normal aging: Implications for Parkinson's disease
Authors: Sawle G. V. , Colebatch J. G. , Shah A. , Brooks D. J. , Marsden C. D. , Frackowiak R. S. J. 
Published: January 2005

AbstractCentral to several current theories of the etiology of Parkinson's disease is the premise that the nigrostriatal dopaminergic system degenerates with normal aging. Much of the evidence for this assertion has come from postmortem neurochemical studies. We have used L‐6‐[18F]fluoro‐Dopa and positron emission tomography in 26 healthy volunteers (age range, 27–76 years) to examine striatal and frontal cortical tracer uptake. Data have been analyzed by using a graphical approach to calculate an influx constant (Ki) for L‐6‐[18F]fluoro‐Dopa uptake into the caudate, putamen, and medial frontal cortex of each subject. In the population studied, there was no decline in Ki with age for any of these structures. A series of physiological measurements made on the older subjects also showed few significant changes with age. The positron emission tomographic findings demonstrate preservation of nigrostriatal dopaminergic function in normal aging. The pathological process causing Parkinson's disease may operate closer to the time of presentation than has been suggested.