bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal RNA in relation to alz‐50 immunoreactivity in alzheimer's disease
Authors: Doebler J. A. , Markesbery W. R. , Anthony A. , Davies P. , Scheff S. W. , Rhoads R. E.
Published: January 2005

Both defective nucleic acid metabolism/protein synthesis and the expression of an abnormal antigen recognized by the Alz‐50 antibody may be involved in the neuronal degeneration of Alzheimer's disease (AD). A multiparametric analysis involving Alz‐50 immunocytochemistry and azure B–RNA microdensitometry was developed to compare nucleic acid alterations in Alz‐50‐positive neurons to those in Alz‐50‐negative neurons of the brain of AD patients. Alz‐50‐immunoreactive neurons of the hippocampal endplate (Rose's H3‐H5 fields) and the subiculum exhibited significantly lower (by approximately 30%) total RNA contents than negative neurons of the corresponding region. The mean RNA content of Alz‐50‐positive neurons of the AD brain was also reduced in comparison to that of Alz‐50‐negative neurons of agematched, nondemented controls, whereas there were no significant differences between negative neurons of AD patients and controls. The hippocampus of nondemented controls was also found to contain Alz‐50‐immunoreactive neurons, although 20‐to 30‐fold fewer than the hippocampus of AD patients. In the controls, there was also a tendency toward reduced RNA levels in Alz‐50‐positive versus ‐negative neurons. These data suggest a relationship between Alz‐50 immunoreactivity and defective nucleic acid metabolism in the AD brain.
Cyclosporine versus azathioprine in the long‐term treatment of multiple sclerosis—results of the german multicenter study
Authors: Kappos L. , Patzold U. , Dommasch D. , Poser S. , Haas J. , Krauseneck P. , Malin J.‐P. , Fierz W. , Graffenried B. U. , Gugerli U. S.
Published: January 2005

In a double‐blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty‐five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self‐evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long‐term immunosuppressive treatment of relapsing‐remitting and relapsing‐progressive multiple sclerosis.
Expression of immunoreactive major histocompatibility complex products in human skeletal muscles
Authors: Karpati George , Pouliot Yannick , Carpenter Stirling
Published: January 2005

Immunoreactive class 1 and class 2 major histocompatibility complex gene products (MHCP) and β2 microglobulin (β2MG) were demonstrated by microscopic immunocytochemistry in cryostat sections of skeletal muscle biopsies of 67 patients with various neuromuscular diseases. Diagnoses included normal muscle, chronic partial denervation, Duchenne dystrophy, polymyositis, dermatomyositis, inclusion body myositis, and miscellaneous neuromuscular diseases. Normal mature muscle fibers did not express MHCP, but blood vessels showed both class 1 and 2 MHCP and β2MG. Regenerating muscle fibers showed consistent sarcolemmal class 1 MHCP expression irrespective of the disease. In polymyositis, the majority of extrafusal muscle fibers of most patients showed strong sarcolemmal class 1 MHCP expression. In dermatomyositis, muscle fibers situated either in perifascicular or in randomly clustered distribution revealed strong class 1 MHCP reactivity. In inclusion body myositis, scattered small clusters of muscle fibers were positive for class 1 MHCP. In polymyositis and inclusion body myositis, particularly strong class 1 MHCP expression was invariably seen in nonnecrotic muscle fibers partially invaded by lymphocytes whose cytotoxic effects are believed to be class 1 MHCP restricted. Factors or agents that trigger class 1 MHCP expression are presumed also to sensitize lymphocytes to muscle fibers in these diseases, but their identity remains obscure at this time. In dermatomyositis, the expression of MHCP in perifascicular muscle fibers and in areas of capillary loss may represent the triggering of MHCP expression by a nonspecific cellular stress reaction, in this case probably low‐grade ischemia.
Metabolic mapping of the oculomotor system in MPTP‐Induced parkinsonian monkeys
Authors: Ho Victor W. , Porrino Linda J. , Crane Alison M. , Burns Richard S. , Kopin Irwin J. , Sokoloff Louis
Published: January 2005

The quantitative autoradiographic 2‐{14C}deoxyglucose method was used to map the distribution of alterations of local cerebral metabolic rate for glucose (lCMRGlc) in the oculomotor system of l‐methyl‐4‐phenyl‐1,2,3,6‐ tetrahydropyridine‐(MPTP)‐induced parkinsonian monkeys. The lCMRGlc was decreased in the frontal eye fields and in the paralamellar mediodorsal thalamus in the parkinsonian monkeys as compared to normal controls. No changes in lCMRGlc were observed in other areas of the oculomotor system. L‐Dopa therapy reversed the oculomotor symptoms in these monkeys, as well as the decrease of lCMRGlc in the frontal eye fields and the paralamellar mediodorsal thalamus. Because the frontal eye fields are known to be involved in the initiation of voluntary saccades, these findings suggest a functional anatomical basis for the oculomotor deficits in Parkinson's disease.
Hearing loss in myotonic dystrophy
Authors: Wright Robert B. , Glantz Russell H. , Butcher Jaynee
Published: January 2005

Seventeen of 25 patients with myotonic dystrophy had moderate to severe hearing loss, usually sensorineural, that was identified by routine audiometric screening and was treatable in some patients. Further testing failed to reveal a single pathophysiological process.
A new technique for interpreting the BAER in cochlear disease
Authors: Tomasulo Richard A. , Peele Pamela B.
Published: January 2005

We found, by studying 20 normal ears and 34 ears with cochlear disease, that the brainstem auditory evoked response (BAER) wave I latency was a good predictor of the I‐V interval (r = −0.67, p< 0.001), whereas hearing loss had little predictive value. The normal and hearingloss groups generated regression lines (wave I latency vs I‐V latency) that did not differ significantly from each other. A normal range of I‐V intervals can be established for any wave I latency, increasing the sensitivity of the BAER.
Immunotherapy of multiple sclerosis
Authors: Weiner Howard L. , Hafler David A.
Published: January 2005

Based on the assumption that multiple sclerosis is an autoimmune disease, a number of clinical trials designed to suppress the immune system or to restore immune balance in multiple sclerosis have been attempted. Depending on the disease category, the clinical goals of immunotherapy differ. Therapeutic goals include improving recovery from acute attacks, preventing or decreasing the number of relapses, and halting the disease in its progressive stage. The ultimate goal of multiple sclerosis therapy is the early treatment of patients in an attempt to halt the onset of progression. Specific strategies of immunotherapy include generation of a suppressor influence, removal of helper/inducer cells, manipulation of activated T cells, manipulation of class II major histocompatibility complex‐bearing cells, alteration of lymphocyte traffic, extracorporeal removal of serum factors or cells, and manipulation of antigenspecific cells. Present treatment modalities are beginning to show some efficacy of nonspecific immunosuppression, but these treatments are limited by their toxicities. As the immunotherapy of multiple sclerosis moves to the next stage in the coming years, patients at an earlier stage of their disease will have to be treated, nontoxic forms of therapy developed, clinical trials lengthened, and a laboratory monitor of the disease developed. Given the positive effects of immunotherapy seen thus far in the disease, it is possible that appropriate immunotherapeutic intervention may provide effective treatment for the disease in the future.
The effects of tobacco smoking on smooth pursuit eye movements
Authors: Sibony Patrick A. , Evinger Craig , Manning Karen A.
Published: January 2005

It has recently been shown that tobacco smoking in normal human subjects induces a transient primary‐position upbeat nystagmus. We studied the effects of tobacco smoking on smooth pursuit eye movement and found defects in both vertical and horizontal tracking during the first 5 minutes after smoking one cigarette. The smooth pursuit defect consisted of a reduction in upward tracking velocity and the superposition of saccadic square‐wave jerks on both vertical and horizontal tracking eye movements. The degree of impairment in upward smooth pursuit correlated with the intensity of tobacco‐induced nystagmus present when recording in darkness. We suggest that these alterations are due to summation of nystagmus on normal tracking eye movements rather than primary defects in the smooth pursuit system.
Trigeminal evoked potentials following brief air puff: Enhanced signal‐to‐noise ratio
Authors: Hashimoto Isao
Published: January 2005

Trigeminal somatosensory evoked potentials (TSEPs) were studied by using fast‐rising air puffs generated by a highspeed air control system. Within 100 ms, air puff stimulation of the face elicited three negative and three positive components over the contralateral, as well as the ipsilateral, sensory area. The air puff TSEPs showed a uniform change in peak latencies and amplitudes as a function of stimulus intensity. The bilateral distribution of the TSEPs stands in sharp contrast to the exclusively contralateral distribution of the SEPs to stimulation of the hand. Air puffs evoked a larger response than electrical stimulation, although the latency remained the same. Unlike electrical stimuli, air puff induces neither stimulus nor muscle artifacts. This, combined with the higher amplitude of the recorded response, enhances the signal‐to‐noise ratio.
Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro
Authors: Selmaj Krzysztof W. , Raine Cedric S.
Published: January 2005

Recombinant human tumor necrosis factor (rhTNF) has been tested for its effect on myelinated cultures of mouse spinal cord tissue. As controls, recombinant human interferon gamma (rhIFN) and interleukin‐2 (rhIL‐2) were tested, as well as T‐cell supernatants, antigalactocerebroside serum, and normal culture medium. It was found that rhTNF induced delayed‐onset (18–24 hr) oligodendrocyte necrosis and a type of myelin dilatation peculiar to this system. Some nerve fibers progressed to demyelination by 72 hours. The myelin dilatation was not reversible by return to normal feeding solution for 3 days. In contrast, rhIFN, rhIL‐2, T‐cell supernatants, and normal medium had little or no effect on cultures. This mechanism differs from other immune‐mediated mechanisms in that it appears that a physiological (not structural) demyelination occurs initially without overt destruction of the myelin sheath. These observations are relevant to the evolution of the multiple sclerosis plaque: dysfunction of ionic channels might contribute to the eventual demise of oligodendrocytes and axons in the longstanding lesion.
Changes in benzodiazepine receptors in alzheimer‐type dementia
Authors: Shimohama Shun , Taniguchi Takashi , Fujiwara Motohatsu , Kameyama Masakuni
Published: January 2005

We studied benzodiazepine receptors in brains obtained at autopsy from 7 normal controls and 7 patients with Alzheimer‐type dementia, using 3H‐flunitrazepam as a ligand. Compared with controls, 3H‐flunitrazepam binding sites were significantly reduced in number in frontal and temporal cortex and hippocampus in the Alzheimer‐type dementia brains. These results suggest that there are significant changes in the number of benzodiazepine receptors in selected brain regions of patients with Alzheimer‐type dementia.
Hypothalamic hamartomas and ictal laughter: Evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging
Authors: Berkovic S. F. , Andermann F. , Melanson D. , Ethier R. E. , Feindel W. , Gloor P.
Published: January 2005

Detailed study of 4 patients and review of the literature allowed us to delineate further the epileptic syndrome associated with hypothalamic hamartomas, which characteristically begins in infancy with laughing seizures. Because early childhood psychomotor development is usually normal, the condition appears benign and may not even be recognized. The episodes of laughter are brief, frequent, and mechanical in nature. These features distinguish it from other forms of epileptic laughter, particularly that which occurs in temporal lobe epilepsy. Subsequently, the seizures become longer, other seizure types appear, and between the ages of 4 and 10 years, the clinical and electroencephalographic features of secondary generalized epilepsy develop. Cognitive deterioration occurs and severe behavior problems are frequent. Prognosis for seizure control and social adjustment is poor. Cortical abnormality occurs in association with the hypothalamic hamartoma. The lesions are best detected by magnetic resonance imaging but may be difficult to identify by computed tomographic scanning.
An antineuronal autoantibody in paraneoplastic opsoclonus
Authors: Budde‐Steffen Corinna , Anderson Neil E. , Rosenblum Mark K. , Graus Francesc , Ford David , Synek Beth J. L. , Wray Shirley H. , Posner Jerome B.
Published: January 2005

Sera from 7 patients with paraneoplastic opsoclonus were examined for antineuronal autoantibodies. An antibody against neuronal nuclei was found in serum from a patient with breast cancer, opsoclonus, and ataxia. This antibody recognized 53‐ to 61‐kDa and 79‐ to 84‐kDa antigens in immunoblots of neurons. Anti‐neuronal antibodies were not found in other patients with paraneoplastic opsoclonus.
Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings
Authors: Kluin Karen J. , Gilman Sid , Markel Dorene S. , Koeppe Robert A. , Rosenthal Guy , Junck Larry
Published: January 2005

We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (ICMRGlc) in is patients with olivepenetecerebeilar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. 1CMRGlc was measured with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the 1CMRG1c within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and 1CMRG1c in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.
Neurofibrillary tangle formation in the nucleus basalis of meynert ipsilateral to a massive cerebral infarct
Authors: Kato Takeo , Hirano Asao , Katagiri Tadashi , Sasaki Hideo , Yamada Shigeru
Published: January 2005

Two cases of massive cerebral infarct in the territory of the middle cerebral artery on one side of the brain are presented, in which many (Patient 1) or several (Patient 2) neurofibrillary tangle‐bearing neurons were observed in the nucleus basalis of Meynert (nbM), ipsilateral to the infarcts. Tangles were absent or rare in the opposite nbM or in other areas of the brain. Considering the widespread projection of nbM axons to the ipsilateral cerebral cortex, this suggests that formation of neurofibrillary tangles can occur as a retrograde reaction of nbM neurons secondary to massive, old cerebral infarction.
Treatment of patients with neuropathy and anti‐MAG IgM M‐proteins
Authors: Nobile‐Orazio E. , Baldini L. , Barbieri S. , Marchmiroli P. , Spagnol G. , Francomano E. , Scarlato G.
Published: January 2005

Five patients with neuropathy and IgM M‐proteins that reacted with myelin‐associated glycoprotein (MAG) were treated for 10 to 20 months with cytostatic agents. In 2 patients, a Decemberrease in serum M‐protein and in anti‐MAG IgM levels coincided with a progressive improvement of neuropathy. No clinical improvement and no Decemberrease of anti‐MAG IgM were observed in the other patients. The close relationship between the Decemberrease of anti‐MAG, M‐proteins and clinical improvement in these patients supports the pathogenetic role of the M‐protein in the neuropathy.
Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography
Authors: Foster Norman L. , Gilman Sid , Berent Stanley , Morin Elizabeth M. , Brown Morton B. , Koeppe Robert A.
Published: January 2005

Progressive supranuclear palsy (PSP) is characterized by supranuclear palsy of gaze, axial dystonia, bradykinesia, rigidity, and a progressive dementia. Pathological changes in this disorder are generally restricted to subcortical structures, yet the type and range of cognitive deficits suggest the involvement of many cerebral regions. We examined the extent of functional impairment to cerebral cortical and subcortical structures as measured by the level of glucose metabolic activity at rest. Fourteen patients with PSP were compared to 21 normal volunteers of similar age using18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography. Glucose metabolism was reduced in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum in the patients with PSP as compared to the normal subjects. Analysis of individual brain regions revealed significant Decemberlines in cerebral glucose utilization in most regions throughout the cerebral cortex, particularly those in the superior half of the frontal lobe. Decemberlines in the most affected regions of cerebral cortex were greater than those in any single subcortical structure. Although using conventional neuropathological techniques the cerebral cortex appears to be unaffected in PSP, significant and pervasive functional impairments in both cortical and subcortical structures are present. These observations help to account for the constellation of cognitive symptoms in individual patients with PSP and the difficulty encountered in identifying a characteristic psychometric profile for this group of patients.
Dual‐label immunocytochemistry of the active multiple sclerosis lesion: Major histocompatibility complex and activation antigens
Authors: Hayashi T. , Morimoto C. , Burks J. S. , Kerr C. , Hauser S. L.
Published: January 2005

Fresh‐frozen autopsy material containing active inflammatory lesions from 9 different patients with multiple sclerosis (MS) was analyzed by immunocytochemistry using a panel of monoclonal antibodies, and a dual‐label immunocytochemical method was developed which permitted the simultaneous detection of two different surface Marchkers on a single cell. We now report the following. (1) The predominant T‐cell phenotype within MS lesions is CD2,3,8. This phenotype Marchks the suppressor‐cytotoxic subset. (2) These cells do not express the natural killer cell Marchker NKH‐1, which is present on a subset of CD8‐positive cells in peripheral blood. (3) The infiltrating cell expresses class I (HLA A, B, C), but not class II (DR and DQ), major histocompatibility complex (MHC) molecules. (4) Other T‐cell surface molecules, including the activation antigens interleukin‐2 receptor, Ta1, and Tll‐3, as well as the Marchker 2H4, are largely not expressed. (5) Endothelial cells express both class I and class II MHC molecules and the 4B4 molecule in both MS and control tissue. (6) Astrocytes within the vicinity of MS lesions are predominantly class II MHC—negative. These results demonstrate that the T‐cell infiltrate present in MS tissue on autopsy has a restricted phenotypic profile, but they also raise the possibility that, within this population, few activated effector cells are present.
Somatosensory potentials evoked by magnetic stimulation of lumbar roots, cauda equina, and leg nerves
Authors: Tsuji Sadatoshi , Murai Yoshiyuki , Yarita Masaru
Published: January 2005

Cortical somatosensory evoked potentials (Septembers) were studied by noninvasive magnetic stimulation at T‐10, T‐12, and L‐5 vertebral levels and in mid‐gluteus muscle and ankle in 27 normal subjects and 7 patients with neurological diseases. Cortical components P2 and N2 were recorded in all normal subjects. The mean peak latencies of P2 were 20.3 ± 0.9 (standard deviation), 21.1 ± 1.2, 23.5 ± 1.4, 27.9 ± 2.0, and 38.1 ± 1.8 msec at the T‐10, T‐12, L‐5, mid‐gluteal and ankle sites of stimulation, respectively. No substantial difference in morphology of P2 and N2 was seen between magnetic and electrical stimulation at T‐12. Amplitudes of P2 and N2 were maximal after magnetic stimulation at motor threshold. P2 and N2 may originate from the sensory cortex. P2 and N2 evoked by T‐10 and T‐12 stimulation were normal in peak latency and morphology in patients with polyneuropathy or polyradiculoneuropathy. Peak latencies of P2 and N2 evoked by T‐10 and T‐12 stimulation were significantly delayed in patients with myelopathy. The patients with radiculopathy showed a delayed peak latency and conduction time of P2 evoked by L‐5 stimulation. Magnetic stimulation of spinal root is able to detect lesions of spinal cord noninvasively.
Organization, fine structure, and viability of the human adrenal medulla: Considerations for neural transplantation
Authors: Hansen John T. , Notter Marchy F. D. , Okawara Shige‐Hisa , Gash Don M.
Published: January 2005

Recent reports of adrenal medullary autografts in patients with Parkinson's disease raise several important questions with respect to the cell types actually being transplanted as well as the potential for chromaffin cell banking prior to neural transplantation. In this study, we determined the general morphological characteristics of the human adrenal medulla and assessed factors important for the maintenance of cultured chromaffin cells for later use as transplants. The human adrenal medulla contained islands of cortical cells scattered throughout the gland as well as Schwann cells, nerve endings, endothelial cells, pericytes, isolated ganglionic neurons, and connective tissue elements such as fibroblasts and smooth muscle cells. Because many of these cell types are mitotically active, transplantation of medullary fragments that contain these cells could have far‐reaching consequences. One approach that could circumvent the problems arising from multiple cell types in the medulla is differential plating of chromaffin cells prior to transplantation. Differential plating yielded relatively pure populations of chromaffin cells that demonstrated excellent viability if processed within 2 hours after cessation of the gland's circulation. Chromaffin cells cultured in the presence of nerve growth factor exhibited a neuronal phenotype, possessed catecholamine histofluorescence, and displayed tyrosine hydroxylase‐ and dopamine β‐hydroxylase—like immunoreactivity. The sex and age of the donor did not affect cell viability or morphological characteristics.
The Go—No‐Go paradigm in attention deficit disorder
Authors: Trommer Barbara L. , Hoeppner Jo‐Ann B. , Lorber Rudy , Armstrong Kevin J.
Published: January 2005

We administered the go—no‐go paradigm to 44 boys with attention deficit disorder (ADD) and 32 control subjects who did not have ADD. This task requires a subject to emit a simple motor response to one cue while inhibiting the response in the presence of another cue. Commission errors suggest impulsivity, and omission errors suggest inattention. ADD subjects made more total errors than did control subjects (p < 0.03), and more ADD subjects made multiple errors (p < 0.001). Within the ADD group, the nonhyperactive (ADDnoH) subjects were characterized by a high number of commission errors early, and significant improvement with practice (p < 0.01). In contrast, the hyperactive ADD subjects (ADD/H) did not differ from control subjects in number of early commission errors, but differed from both control subjects and ADDnoH subjects in their failure to improve with practice. In addition, the incidence of omission errors was highest in the ADD/H group. This paradigm can be easily incorporated into the assessment of children with suspected ADD and provides an objective measure of inattention and impulsivity. Our data provide cognitive support for the empirical distinction between hyperactive and nonhyperactive children with ADD.
Posture in Parkinson's disease: Impairment of reflexes and programming
Authors: Dietz V. , Berger W. , Horstmann G. A.
Published: January 2005

The leg muscle electromyographic responses induced during stance by impulsive displacements of a treadmill belt (directed forward or backward and at different rates) were studied in a group of patients with Parkinson's disease and a group of age‐matched healthy subjects. Young normal subjects were also studied both before and after intake of a dopamine antagonist (haloperidol). Compensatory gastrocnemius electromyographic responses resulting from backward‐directed displacements were significantly smaller in both the patients and the young normal subjects following intake of haloperidol. The reduced sensitivity of the gastrocnemius muscle to stretch correlated with an inability to compensate for the perturbations. In the patients, the gastrocnemius response was followed by enhanced activation of the tibialis anterior muscle. This was not the case in the normal subjects after intake of dopamine antagonist and is probably not, therefore, the consequence of acute dopamine deficiency. In the patients the angular rotation at the ankle joint induced during faster backward‐directed displacements was slower than that in normal subjects, despite identical amounts of gastrocnemius electromyographic activity. This supports earlier findings of changes in intrinsic muscle stiffness in Parkinson's disease. None of these differences were seen when the tibialis anterior muscle was stretched. This differential behavior of the antagonist leg muscles can best be explained by the different function fulfilled by these muscles in regulation of stance and gait.
Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey
Authors: Shimoyama Ichiro , Dauth George W. , Gilman Sid , Frey Kirk A. , Penney John B.
Published: January 2005

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (lCMRGlc) is Decemberreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral Decemberreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.
Chronic remitting‐relapsing experimental allergic encephalomyelitis induced in monkeys with homologous myelin basic protein
Authors: Shaw Cheng‐Mei , Alvord Ellsworth C. , Hruby Sarka
Published: January 2005

A chronic remitting‐relapsing form of experimental allergic encephalomyelitis (EAE) has been produced in monkeys sensitized to homologous myelin basic protein in Freund's complete adjuvants by the technique of suboptimal treatment after the onset of disease. Not only does the clinical course resemble that of human multiple sclerosis more closely than does the clinical course of acute EAE, but so also does the histological reaction, with more‐nearly pure demyelination, rather than the hyperacute hemorrhagic‐necrotic lesions that occur so commonly in untreated monkeys with ordinary acute EAE.
A comparison of somatosensory evoked and motor evoked potentials in stroke
Authors: Macdonell R. A. L. , Donnan G. A. , Bladin P. F.
Published: January 2005

Nineteen patients with radiologically confirmed stroke, and varying degrees of hemiparesis, were studied using somatosensory evoked potentials and the recently developed technique of transcutaneous motor cortex stimulation. The functional deficit caused by stroke was assessed at the time of evoked potential testing and again on follow‐up 2 months after stroke. Stroke location and degree of recovery were compared with the evoked potentials elicited an average of 8 days after the acute event. The motor response was better (p < 0.01) than somatosensory response at predicting an outcome in terms of functional recovery, both overall and when comparing patients with similar degrees of weakness. Normal somatosensory evoked potentials also predicted recovery but were not as sensitive as the motor evoked potentials (0.01 < p < 0.05). Motor evoked potentials in conjunction with clinical assessment may offer a means of more accurately predicting functional outcome following stroke than can be achieved with clinical assessment, with or without somatosensory evoked potentials. The additional finding that cortically evoked motor evoked potentials were delayed only by subcortical lesions is of interest and may extend the understanding of the pathophysiological mechanism of this response in humans.
Intraventricular hemorrhage in the premature infant—current concepts. Part II
Authors: Volpe Joseph J.
Published: January 2005

Diagnosis of periventricular‐intraventricular hemorrhage (IVH) and its neuropathological consequences and accompaniments in the living infant has been facilitated greatly by the introduction of real‐time cranial ultrasonography. The major advantages of the technique include high‐resolution capability, portable instrumentation, lack of ionizing radiation, and relative affordability. Prognosis in infants with IVH relates to the mechanisms of brain injury, the most important of which are prior hypoxic‐ischemic insults, posthemorrhagic hydrocephalus, and periventricular hemorrhagic infarction. The last of these is most critical and it is now clear that careful quantitative assessment of the ultrasonographic appearance of the periventricular parenchyma in the infant with IVH during the acute period of illness is of major value in estimating outcome. Prevention of IVH remains the most important goal. Prenatal interventions include prevention of premature birth (currently a very elusive goal in the United States), transportation of the premature infant to a tertiary facility in utero rather than after birth (an approach of proven value), prenatal administration of phenobarbital or vitamin K (initially promising data that require confirmation and amplification), and optimal management of labor and delivery. Postnatal interventions include careful resuscitation of newborns, correction of fluctuating cerebral blood flow velocity, correction or prevention of other major hemodynamic disturbances, and correction of abnormalities of coagulation. Of these interventions the use of muscle paralysis to correct fluctuating cerebral blood flow velocity has shown the most striking benefit vis‐à‐vis prevention of IVH. Postnatal pharmacological interventions that have been studied in detail include the use of phenobarbital, indomethacin, ethamsylate, and vitamin E. No single agent among this group has been shown consistently to lead to a decrease in incidence and severity of IVH. The most promising current data relate to the postnatal administration of ethamsylate (which is not available in the United States). Inconsistent results have been obtained in the study of postnatal administration of phenobarbital, indomethacin, and vitamin E. At present, no pharmacological agent is considered to have benefits that are established clearly enough to warrant recommendation for routine use in premature infants.
Effect of digitalis on central demyelinative conduction block in vivo
Authors: Kaji Ryuji , Sumner Austin J.
Published: January 2005

In searching for agents effective in treating multiple sclerosis, we studied the effect of a short‐acting digitalis, ouabain, on conduction block in an animal model of central nervous system demyelination. The electrogenic sodium/potassium pump, which digitalis specifically inhibits, is responsible for part of the resting membrane potential and also the activity‐related membrane hyperpolarization following high‐frequency impulses. The latter causes intermittent conduction block in demyelinated fibers. Therefore, digitalis might be expected to reverse demyelinative conduction blocks by reducing the threshold at the blocking node. Somatosensory evoked potentials were monitored in 11 rats with spinal cord demyelination before and after systemic administration of ouabain (0.1–0.6 mg or 0.21–1.58 mg/kg IP). In all rats, slowed conduction velocity of the compound action potential through the lesion was significantly reversed, and failure to transmit high‐frequency impulses was improved upon. The amplitude of the cortical somatosensory evoked potentials also increased significantly. Digitalis is a promising therapeutic agent for trial in patients with multiple sclerosis.
Neocortical propagation in temporal lobe spike foci on magnetoencephalography and electroencephalography
Authors: Sutherling W. W. , Barth D. S.
Published: January 2005

Propagation of the neuronal population of the interictal epileptic spike was quantified in 5 patients with complex partial epilepsy arising from temporal lobe using electroencephalography and magnetoencephalography. During the spike complex in each patient there was a spike at the deep sphenoidal electrode and a spike at the superficial scalp electrode on spontaneous electroencephalography. In each patient the sphenoidal spike had a different peak latency than the scalp spike, consistent with spike propagation. Electroencephalography was used to trigger two magnetoencephalographic averages of stereotyped spikes during the sphenoidal peak and the scalp peak. Magnetoencephalography discriminated the centers of two cortical spike populations at different latencies, showing deeper localization with sphenoidal trigger and more superficial localization with scalp trigger in each patient (p < 0.05). Latency differences and propagation distances of spikes were consistent with the conduction velocity of corticocortical fibers. Noninvasive estimates of the cortical surface area of the spikes agreed with estimates obtained by electrocorticography over temporal neocortex. These findings indicate propagation of neuronal populations active during human interictal spikes between deep and superficial cortex of temporal lobe, likely by monosynaptic or oligosynaptic pathways. This interictal system appears to be partly independent of the hippocampal interictal system in complex partial epilepsy.
Infarcts of undetermined cause: The NINCDS stroke data bank
Authors: Sacco R. L. , Ellenberg J. H. , Mohr J. P. , Tatemichi T. K. , Hier D. B. , Price T. R. , Wolf P. A.
Published: January 2005

In a prospective study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, the 1,273 with infarction were classified into diagnostic subtypes. Diagnosis was based on the clinical history, examination, and laboratory tests including computed tomography, noninvasive vascular imaging, and where safe and relevant, angiography. Five hundred and eight cases (fully 40%) were labeled as infarcts of undetermined cause (IUC), of which 138 (27%) were evaluated with both computed tomography and angiography. The clinical syndrome and computed tomographic and angiographic findings in 91 (65.9%) of these 138 IUC cases were clearly not attributable to large‐artery thrombosis and could permit reclassification of the infarct as due to some form of embolism. Failure to define a source of embolus kept them in the category of IUC. Thirty‐one cases (22.5%) could be reclassified as due to stenosis or thrombosis of a large artery, and 16 (11.6%) as lacunar infarction. To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses, a stepwise multiple logistic model was used. The most important characteristics were young age, presence of a superficial infarct, prior transient ischemic attack, low weakness score, and presentation with a nonlacunar syndrome. The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis. Continued use of the category IUC may help clarify risk factors and stroke subtypes, allow new mechanisms of ischemic stroke to be uncovered, and prevent classification categories of stroke used in clinical trials from becoming too broad.
Progressive aphasia without dementia: Further documentation
Authors: Sapin Linda R. , Anderson Frank H. , Pulaski Philip D.
Published: January 2005

Two patients with progressive aphasia without dementia had magnetic resonance imaging findings of focal left temporal lobe abnormality. Unlike most of the other documented cases of progressive aphasia, onset was not presenile, occurring at ages 68 and 69.
Results of surgical treatment in patients with bitemporal epileptiform abnormalities
Authors: So Norman , Olivier André , Andermann Frederick , Gloor Pierre , Quesney L. Felipe
Published: January 2005

Fifty‐three of 57 patients who had evidence of bitemporal epileptiform abnormalities and who required investigation with stereotactic depth electroencephalography (SDEEG) recordings to determine the site of origin of seizures underwent surgical resection for the treatment of their epilepsy. A minimum of 2 years' follow‐up was available in 48 patients who underwent a temporal lobe resection. In this group, 19 patients (40%) were greatly improved, and of these 14 (29%) became seizure free and 5 (10%) had no more than 3 seizures each year. Another 22 patients (46%) showed a worthwhile reduction in seizure frequency of at least 50%. Seven patients (15%) were not significantly improved. An etiological factor of early convulsions before age 3 (usually febrile) was associated with a better outcome. Both the lack of a strong predominance for SDEEG‐recorded seizures to arise in the resected temporal lobe and the presence of residual epileptiform abnormalities in the postexcision electrocorticogram were correlated with poorer results.
Hereditary long Q‐T syndrome presenting as epilepsy: Electroencephalography laboratory diagnosis
Authors: Gospe Sidney M. , Choy Michael
Published: January 2005

Patients with hereditary Q‐T interval prolongation can present with seizures, syncope, and sudden death. In 2 siblings with autosomal dominant familial long Q‐T syndrome, electroencephalographic examinations performed 6 and 2 years before diagnosis included electrocardiographic tracings documenting the cardiac abnormality. A timely diagnosis of this condition may have prevented the death of 1 of these patients. Measurement of the corrected Q‐T interval on electrocardiographic tracings obtained in the electroencephalography laboratory should be considered in selected patients.
Xenon computed tomography measuring cerebral blood flow in the determination of brain death in children
Authors: Ashwal Stephen , Schneider Sanford , Thompson Joseph
Published: January 2005

Local cerebral blood flow was measured using stable xenon computed tomography in 21 children, 10 of whom were clinically brain dead and had electrocerebral silence as determined by electroencephalography. Radioisotopic brain scanning in 9 patients showed no visible cerebral activity in all patients and minimal residual sagittal sinus activity in 4. In this population, mean cerebral blood flow as measured by xenon computed tomography was 1.3 ± 1.6 ml/min/100 gm. Respiratory support was discontinued in 8 patients, and 2 patients had cardiac arrest. Eleven profoundly comatose children who did not meet all clinical criteria for brain death and who had markedly suppressed but not isoelectric electroencephalograms had an average cerebral blood flow of 33.5 ± 16.3 ml/min/100 gm as determined by xenon computed tomography. Flows in this group ranged from 11.8 ± 4.1 to 62.3 ± 1.9 ml/min/100 gm. There was no difference in cerebral blood flow in those children who survived (30.4 ± 16.3 ml/min/100 gm; n = 7) compared with those who died acutely (38.3 ± 14.3 ml/min/100 gm; n = 4). Two patients who survived had average total flows of only 11.8 and 12.1 ml/min/100 gm. Our findings suggest that in infants and children older than 1 month, (1) cerebral blood flow below approximately 10 ml/min/100 gm is consistent with clinical brain death, (2) cerebral blood flow of less than 5 ml/min/100 gm is consistent with no flow as demonstrated by radionuclide techniques, and (3) flow of more than 10 to 15 ml/min/100 gm is associated with the potential for survival.
Peripheral pharmacokinetics of apomorphine in humans
Authors: Gancher Stephen T. , Woodward William R. , Boucher Brian , Nutt John G.
Published: January 2005

Apmorphine, a potent dopamine agonist, has been used in acute and chronic studies of parkinsonism and other neurological disorders. To define its peripheral pharmacokinetics, we administered apomorphine by subcutaneous injection, by subcutaneous infusion, and by intravenous infusion to 15 patients with parkinsonism and measured plasma apomorphine levels by high‐performance liquid chromatography with electrochemical detection. The peak drug levels and area under the curve were closely correlated with the dose administered; time to peak was brief and was independent of dose. The variation in absorption was high between subjects but low within individual subjects. In 11 of 15 subjects, the disappearance of drug could be described by a two‐compartment model, with a distribution half‐life of 5 minutes and an elimination half‐life of 33 minutes. The drug absorption, volume of distribution, plasma clearance, and half‐lives were similar for subcutaneous injection, subcutaneous infusion, and intravenous infusion. We conclude that apomorphine is rapidly and completely absorbed from subcutaneous tissue, correlating with the rapid onset of clinical effects, and that the brief duration of clinical action of the drug is explained by its rapid clearance.
Amyotrophic lateral sclerosis: An unconventional autoimmune disease?
Authors: Drachman Daniel B. , Kuncl Ralph W.
Published: January 2005

The possibility of an autoimmune mechanism of pathogenesis in amyotrophic lateral sclerosis has long been considered, but the evidence to support a conventional autoimmune process, reviewed here, is inconclusive. However, antibodies that react in vitro with gangliosides have recently been found in sera of a large majority of patients with classical amyotrophic lateral sclerosis and other motor neuron syndromes. A working hypothesis is proposed, suggesting how antibodies might be related to the disease process. The hypothesis attempts to account for (1) a pathogenic role of antibodies directed against the carbohydrate components of glycolipids, (2) the selectivity of the process for motor neurons, (3) an antibody‐mediated mechanism that could result in apparently degenerative neuropathological changes without signs of inflammation, and (4) a type of autoimmune response that is extremely difficult to suppress by conventional means. Although the evidence for this hypothesis is by no means complete, its critical features are all testable.
Activated T cells in HTLV‐I–associated myelopathy: Autologous mixed lymphocyte reaction
Authors: Minato Sei‐ichiro , Itoyama Yasuto , Fujii Naoki , Kira Jun‐ichi , Goto Ikuo , Yamamoto Naoki
Published: January 2005

We examined the autologous mixed lymphocyte reaction in human T‐cell lymphotropic virus type I‐associated myelopathy to elucidate the known increase in spontaneous proliferation of peripheral blood lymphocytes. Proliferative responses in the autologous mixed lymphocyte reaction test were significantly increase (34,205 cpm) in cells from 9 patients with the myelopathy, as compared with findings (18,695 cpm) in the control subjects. When non‐T‐cell fractions were depleted from autologous mixed lymphocyte reaction cultures, proliferative responses were completely suppressed in the control subjects, while proliferation of the peripheral blood lymphocytes from the groups with the myelopathy were not affected by depletion of non‐T‐cell fractions. The increase in spontaneous proliferation of peripheral blood lymphocytes from the groups with the myelopathy were not affected by depletion of non‐T‐cell fractions. The increase in spontaneous proliferation of peripheral blood lymphocytes in patients with the myelopathy is probably not related to an increase in autologous mixed lymphocyte reactions.
Protease nexin I immunostaining in alzheimer's disease
Authors: Rosenblatt Dorrie E. , Geula Changiz , Mesulam M‐Marsel
Published: January 2005

Immunohistochemical experiments showed that a small subset of neuritic plaques in brains affected by Alzheimer's disease stain positively with an antibody to the protease inhibitor protease nexin I. Nearly all plaques and tangles throughout the brain also showed a heightened avidity for a protease nexin I antibody‐antigen aggregate, suggesting that plaques and tangles may have a particularly high density of protease nexin I–binding sites. These observations provide further evidence for a potential disruption of protein processing in the brains of patients with Alzheimer's disease.
Isoelectric focusing studies of serum and cerebrospinal fluid in patients with antecedent poliomyelitis
Authors: Salazar‐Grueso Edgar F. , Grimaldi Luigi M. E. , Roos Raymond P. , Variakojis Renata , Jubelt Burk , Cashman Neil R.
Published: January 2005

The post‐poliomyelitis syndrome (PPS) refers to symptoms of new weakness, fatigue, and pain years after recovery from acute poliomyelitis. Oligoclonal IgG bands have been reported in the cerebrospinal fluid (CSF) from PPS patients, suggesting that the syndrome is immune mediated or caused by persistent viral infection. We studied 15 paired serum and CSF samples and 6 unpaired CSF samples from a total of 21 patients with a prior history of poliomyelitis. Quantitative immune studies failed to show evidence for increased intrathecal IgG production relative to patients with noninflammatory central nervous system (CNS) disease. We found definite oligoclonal IgG bands in the CSF from only 1 patient, who also carried a diagnosis of multiple sclerosis. An isoelectric focusing poliovirus antigen overlay study showed evidence that suggested a CNS‐specific antipoliovirus immune response in only 1 patient. Our results fail to support a dysimmune or persistent viral cause for post‐poliomyelitis progressive muscular atrophy or PPS.