bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain microemboli during cardiac surgery or aortography
Authors: Moody D M. , Bell M. A. , Challa V. R. , Johnston W. E. , Prough D. S.
Published: January 2005

We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium‐sized arterioles. Two other patients had a small number of the same microvascular changes following proximal aortography. Thirty‐four patients and 6 dogs not undergoing cardiopulmonary bypass had none. (A 35th patient who had not undergone cardiopulmonary bypass or aortography showed a small number of dilatations; mediastinal air was a suggested source.) Some of the dilatations exhibited various forms of birefringence. Because most of the dilatations appear empty, we speculate that they are the sites of gas bubbles or fat emboli that have been removed by the solvents used in processing. These microvascular events, occurring only in conjunction with major arterial interventions, may be the anatomical correlate of the neurological deficits or moderate to severe intellectual dysfunction seen in at least 24% of patients after cardiac surgical procedures assisted by cardiopulmonary bypass.
Differing patterns of striatal 18F‐dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy
Authors: Brooks D. J. , Ibanez V. , Sawle G. V. , Quinn N. , Lees A. J. , Mathias C. J. , Bannister R. , Marsden C. D. , Frackowiak R. S. J.
Published: January 2005

Using positron emission tomography (PET), we studied regional striatal 18F‐dopa uptake in 16 patients with L‐dopa‐responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age‐matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F‐dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F‐dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F‐dopa uptake in the anterior and posteior putamen. Caudate 18F‐dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F‐dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F‐dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy. If an akinetic‐rigid patient has equally depressed 18F‐dopa uptake in the caudate and putamen, that person is likely to have neuropathological changes other than those of idiopathic PD.
Human immuno deficiency virus (HIV)–associated myopathy: Immunocytochemical identification of an HIV antigen (gp 41) in muscle macrophages
Authors: Chad David A. , Smith Thomas W. , Blumenfeld Andrew , Fairchild Patrick G. , Degirolami Umberto
Published: January 2005

In a patient with acquired immunodeficiency disease syndrome (AIDS) and muscle biopsy specimen disclosed degeneration of muscle fibers, regeneration, and focal endomysial mononuclear inflammation. A conspicuous feature was the presence of perivascular macrophages within the endomysium that showed positive immunostaining for human immunodeficiency virus (HIV) (gp 41) antigen. HIV was not detected within myofibers. Our findings suggest an important role for the HIV‐infected macrophage in the pathogenesis of this myopathy.
Large‐scale neurocognitive networks and distributed processing for attention, language, and memory
Authors: Mesulam M‐Marsel
Published: January 2005

Cognition and comportment are subserved by interconnected neural networks that allow high‐level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain‐behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.
Brain pH in head injury: An image‐guided 31P magnetic resonance spectroscopy study
Authors: Rango Mario , Lenkinski Robert E. , Alves Wayne M. , Gennarelli Thomas A.
Published: January 2005

It has been suggested that brain acidosis may follow head trauma, and therapies aimed at correcting acidosis have been proposed. Direct measurements of intracellular pH, however, have thus far not been possible in clinical situations. We have studied the intracellular brain pH in 22 patients after head injury (mean Glasgow Coma Score 6.1). Patients were investigated by a combined approach of phosphorus 31 magnetic resonance spectroscopy and magnetic resonance imaging (overall examination time 50–75 min) at a mean time of 11 days after injury (36 hours to 24 days). 31P spectra were obtained in 11 patients on assisted ventilation and in 11 patients on spontaneous ventilation. These spectra were analyzed to yield the pH in the regions studied in all the patients. All pH values were in the normal or alkalotic range when compared with 6 age‐matched normal controls. No differences were found between patients on assisted ventilation and patients on spontaneous ventilation. When analyzed as a group, the brain pH in the focal lesions appeared to increase in the first days, to reach a peak in the alkalotic range in the second week, and to return toward normal within 3 weeks from acute injury. Our results suggest that there is no evidence of posttraumatic intracellular brain acidosis in recent human head injury, and therefore, therapies aimed at alkalinizing brain cells need to be reconsidered.
Respiratory failure and unilateral caudal brainstem infarction
Authors: Bogousslavsky J. , Khurana R. , Deruaz J. P. , Hornung J. P. , Regli F. , Janzer R. , Perret C.
Published: January 2005

We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (Paco2 62 mm Hg, Pao2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses.
Stiff‐man syndrome: A GABAergic autoimmune disorder with autoantigenic heterogeneity
Authors: Gorin Dr F. , Baldwin B. , Tait R. , Pathak R. , Seyal M. , Mugnaini E.
Published: January 2005

Autoantibodies that reacted with cell bodies and axon terminals of gamma‐aminobutyric acid (GABA)ergic neurons were present in the serum and cerebrospinal fluid in a patient with stiff‐man syndrome with type I diabetes. Immunoblot experiments using this patient's serum and cerebrospinal fluid did not corroborate an earlier observation that these autoantibodies are directed against the GABAergic cytosolic enzyme, L‐glutamic acid decarboxylase. While L‐glutamic acid decarboxylase autoantibodies may be associated with this syndrome, they do not appear to be easily demonstrated.
A case‐control study of Alzheimer's disease
Authors: Graves Amy Borenstein , White Emily , Koepsell Thomas D. , Reifler Burton V. , Van Belle Gerald , Larson Eric B. , Raskind Murray
Published: January 2005

A Case‐control study of Alzheimer's disease (AD) was conducted to evaluate the roles of family history of dementing disease and AD, and medical conditions, particularly those related to the viral immune hypotheses in AD. One hundred and eighty‐three clinically diagnosed patients were identified between 1980 and 1985 through the Geriatric and Family Services clinic at the University of Washington hospital, and 18 patients were identified during the same time period through the Veteran's Administration Medical Center in Seattle, Washington. Telephone interviews were conducted with spouses (87.7%) and children (12.3%) of the patients. Each Patient was matched to a friend or non‐blood relative of the patient by age, sex, and the relationship between the patient and his or her respondent, for a total of 130 matched pairs. The odds ratio for AD was elevated if a first‐degree relative was reported to have a history of dementia (odds ratio, 2.21; 95% confidence interval, 1.17 to 4.18). This risk was especially elevated if a sibling was affected (odds ratio, 4.04; 95% confidence interval, 1.37 to 11.90); the highest risk to the proband was observed if a sibling had presumed AD (odds ratio, 5.92; 95% confidence interval, 1.59 to 21.96). The risk increased with increasing numbers of first‐degree family members affected for both a history of dementia and presumed AD. We found little difference between patients and control subjects with respect to the age of the mother or father at the time of the subject's birth. No statistically significant differences were observed between the two groups with regard to conditions that might support the immune and viral hypothesis in AD, smoking, or alcohol problems.
Timing and topography of cerebral blood flow, aura, and headache during migraine attacks
Authors: Olesen Jes , Friberg Lars , Olsen Tom Skyhøj , Iversen Helle K. , Lassen Niels A. , Andersen Allan R. , Karle Agnete
Published: January 2005

Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine). In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations. The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere. Further development of this pathological process was accompanied by the aura symptoms. Thereafter headache occurred while regional cerebral blood flow remained decreased. During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache. In some patients headache disappeared while regional cerebral blood flow remained increased. Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one‐third had bilateral headache. Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere). Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors. Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.
Ataxia and peripheral neuropathy: A benign variant of peroxisome dysgenesis
Authors: Maccollin Mia , De Vivo Darryl C. , Moser Ann B. , Beard Margaret
Published: January 2005

A 5‐year‐old boy with panperoxisomal dysfunction is described. Clinical features included hypotonia, areflexia, and ataxia. Cognition, vision, hearing, and hepatic function were normal. A panel of peroxisomal markers, including very‐long‐chain fatty acids, phytanic acid, pipecolic acid, and catalase compartmentalization, were abnormal. This is a uniquely benign syndrome of disordered peroxisome biogenesis.
Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha
Authors: Miyazaki Masahito , Hashimoto Toshiaki , Fujino Kayo , Goda Tomoko , Tayama Masanobu , Kuroda Yasuhiro
Published: January 2005

An 8‐years‐old boy with subacute sclerosing panencephalitis (SSPE) was treated with 1.0 to 3.0 × 106 IU human interferon alpha (IFN) by the intrathecal route weekly or fortnightly. Pronounced improvement of clinical and electroencephalographic findings were observed in a dose‐dependent manner. Our patient raises hope that IFN can induce sustained remission in patients with SSPE.
Continuous muscle fiber activity, peripheral neuropathy, and thymoma
Authors: García‐Merino A. , Cabello A. , Mora J. S. , Liaño H.
Published: January 2005

Two patients, one of them with myasthenia gravis, presented symptoms of continuous muscle fiber activity syndrome before discovery of a thymoma. Peripheral neuropathy was present in both patients, with axonal and demyelinating lesions in sural nerve biopsy. The syndrome remained unchanged or whose after thymectomy. Both patients died of associated complications.
Regional variation in brain lactate in leigh syndrome by localized 1H magnetic resonance spectroscopy
Authors: Detre John A. , Wang Zhiyue , Bogdan Andrew R. , Gusnard Debra A. , Bay Carolyn A. , Bingham Peter M. , Zimmerman Robert A.
Published: January 2005

Localized water‐suppressed 1H magnetic resonance spectroscopy was performed in an 11‐month‐old infant with Leigh syndrome. Spectra obtained from the basal ganglia, occipital cortex, and brainstem showed elevations in lactate, which were most pronounced in regions where abnormalitites were seen with routine T2‐weighted magnetic resonance imaging. This approach has allowed us to examine metabolism in brain tissue directly and noninvasively, and may provide a sensitive means for evaluating metabolic disease and the response to therapy in the brain.
Anti‐Ri: An antibody associated with paraneoplastic opsoclonus and breast cancer
Authors: Luque F. Antonio , Furneaux Henry M. , Ferziger Reuven , Rosenblum Marc K. , Wray Shirley H. , Schold S. Clifford , Glantz Michael J. , Jaeckle Kurt A. , Biran Haim , Lesser Martin , Paulsen William A. , River Mary E. , Posner Jerome B.
Published: January 2005

The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti‐Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti‐Ri antibody but not with breast cancers from patients without anti‐Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55‐kd and 80‐kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti‐Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small‐cell lung cancer. We conclude that the presence of anti‐Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.
Parent‐child concordance in multiple sclerosis
Authors: Sadovnick A. D. , Bulman D. , Ebers G. C.
Published: January 2005

It is now recognized that susceptibility to multiple sclerosis (MS) is determined in part by genetic factors. The gene loci influencing MS susceptibility are largely unidentified. In an attempt to better understand the mode of transmission, parent‐child concordance for MS was studied in two large, population‐based MS clinic populations. Among 75 parent‐child pairs concordant for MS, we found 40 mother‐daughter pairs, 13 mother‐son pairs, 21 father‐daughter pairs, and 1 father‐son pair. Controlling for the known female preponderance in MS, the data show a paucity of father‐son pairs. These data have implications for understanding the mechanisms of inheritance for MS susceptibility as well as for risk counseling in families of patients.
The hypothalamic lateral tuberal nucleus in Alzheimer's disease
Authors: Kremer Berry , Swaab Dick , Bots Gerard , Fisser Bart , Ravid Rivka , Roos Raymund
Published: January 2005

The hypothalamic lateral tuberal nucleus was investigated in 5 young patients, aged 45 to 64 years, with Alzheimer's disease (AD) and in 5 age‐matched control subjects. Combining conventional histopathological and immunocytochemical staining with neuronal counts, a peculiar form of neuronal pathology was characterized. Although neurons and neurites in the lateral tuberal nucleus of AD specimens were heavily stained by Alz‐50, silver and thioflavine‐S stains disclosed few neurofibrillary tangles or neurites. The numbers of neurons in the lateral tuberal nucleus of patients with AD (67,450; SEM = 5,050) were no different from those of control subjects (58,900; SEM = 2,450). In the AD patients, few plaques were present and were almost exclusively of the amorphous variety. We conclude that neurons in the lateral tuberal nucleus show an early stage of AD‐related cytoskeletal pathology (Alz‐50 positivity), but without plaques or neuronal death.
Anatomical left‐right asymmetry of language‐related temporal cortex is different in left‐ and right‐handers
Authors: Steinmetz Helmuth , Volkmann Jens , Jäncke Lutz , Freund Hans‐Joachim
Published: January 2005

Asymmetry of the planum temporale, a language‐related intrasylvian area on the superior temporal gyrus, is the most remarkable anatomical left‐right asymmetry of the human brain. The in vivo application of magnetic resonance morphometry in 52 healthy volunteers (26 dextrals and 26 sinistrals) revealed that planum temporale asymmetry than right‐handers. Thus, a structural‐functional relation exists in cerebral asymmetry. The correlation is likely to reflect language representation. Because familial sinistrality influenced the anatomical pattern in left‐handers and planum temporale asymmetry is already present in the newborn, prenatal factors must play an important role in the development of functional laterality.
A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy
Authors: Robbins Richard J. , Brines Michael L. , Kim Jung H. , Adrian Thomas , De Lanerolle Nihal , Welsh Susan , Spencer Dennis D.
Published: January 2005

Although neuropeptides have been demonstrated to be hippocampal neuromodulators in laboratory animals, their role in human hippocampal physiology or pathophysiology remains to be defined. The concentrations of somatostatin, cholecystokinin octapeptide, vasoactive intestinal polypeptide, and dynorphin A 1‐17 were determined in hippocampal tissue resected from patients with cryptogenic temporal lobe epilepsy, a common seizure disorder originating in or near the hippocampus. Control tissue was obtained from cadavera or epilepsy patients in whom the hippocampus was removed during the resection of temporal lobe tumors. Peptide determinations were performed on extracts of punch biopsy specimens taken from six different hippocampal regions. A significant decrease in immunoreactive somatostatin concentration was identified in the dentate gyrus and in region cornu ammonis 4 of cryptogenic temporal lobe epilepsy specimens. No significant changes were present in any other hippocampal region or in the levels of other peptides. In situ hybridization studies performed on cryostat sections from similar patients confirmed a marked loss of neurons expressing the somatostatin gene, which was restricted to the dentate hilus. The density of specific 125I‐somatostatin binding to cryostat sections, as determined by semiquantitative in vitro autoradiography, was significantly increased in the dentate gyrus of the cryptogenic epilepsy patients, compared with tumor control specimens. We conclude that a loss of somatostatin‐producing interneurons with an upregulation of dentate somatostatin receptors is a specific and characteristic element in the pathophysiology of human crytogenic temporal lobe epilepsy.
Correction of non–24‐hour sleep/wake cycle by melatonin in a blind retarded boy
Authors: Palm Lars , Blennow Gösta , Wetterberg Lennart
Published: January 2005

A 9‐year‐old, blind boy with severe mental retardation with a chronic sleep/wake disturbance had a circadian rhythm of 24.75 hours and an internal desynchronization of the endogenous rhythms. Treatment with oral melatonin given at 6PM induced a regular sleep/wake pattern. Melatonin, in this patient, convincingly entrained the endogenous rhythm to the appropriate chronological 24‐hour day.
Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography
Authors: Glantz Michael J. , Hoffman John M. , Coleman R. Edward , Friedman Allan H. , Hanson Michael W. , Burger Peter C. , Herndon PhD James E. , Meisler William J. , Schold S. Clifford
Published: January 2005

As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (FDG‐PET) in these difficult diagnostic situations by obtaining FDG‐PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG‐PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG‐PET scanning with[18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F] fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors.
Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilepsy
Authors: Silver Jon M. , Shin Cheolsu , McNamara James O.
Published: January 2005

We sought to determine whether the clinically effective anticonvulsant drug valproate exhibited antiepileptogenic properties in the kindling model (we use the term anticonvulsant to mean suppression of seizure, and antiepileptogenic to mean suppression of development of epilepsy). We compared and contrasted valproate with two other anticonvulsan drugs, phenobarbital and carbamazepine. We investigated the effects of these drugs on the development of kindling that is, the number of stimulation‐induced afterdischarges required to induce enhanced seizure susceptibility in rats Valproate exhibited powerful antiepileptogenic effects as evident in a dose‐dependent increase in the number of afterdischarges required to induce kindling. These effects were not due to retained valproate or an active metabolite merely masking the expression of kindled seizures. By contrast, carbamazepine was devoid of any antiepileptogenic effects despite exhibiting marked anticonvulsant effects. Like valproate, phenobarbital exhibited both antiepileptogenic and anticonvulsant properties, but its antiepileptogenic properties were significantly less pronounced. The antiepileptogenic effects of valproate and phenobarbital strengthen the candidacy of these agents for the clinical studies needed to investigate pharmacological prevention of the development of epilepsy in high‐risk groups.
Change in pattern of muscle activity following botulinum toxin injections for torticollis
Authors: Gelb Douglas J. , Yoshimura Don M. , Olney Richard K. , Lowenstein Daniel H. , Aminoff Michael J.
Published: January 2005

Twenty patients with torticollis had electromyographic studies of their neck muscles performed before and after a series of local injections of botulinum toxin. The pattern of muscle activity changed after the injections, and this effect persisted even after head position had returned to baseline. Patients who did not experience any clinical benefit from the injections also demonstrated a change in the pattern of muscle activity. These results suggest that the underlying abnormality in torticollis usually involves a general motor program for head position, rather than the activity of individual neck muscles.
Eosinophilia myalgia syndrome: I. Immunocytochemical evidence for a T‐cell–mediated immune effector response
Authors: Emslie‐Smith Alison M. , Engel Andrew G. , Duffy Joseph , Bowles Carolyn A.
Published: January 2005

Specimens of muscle and fascia from 13 patients fulfilling the Centers for Disease Control criteria for the eosinophilia myalgia syndrome (EMS) were studied by quantitative immunocytochemical analysis. The immunolocalization of CD3, CD4, CD8, CD22, and CD56 markers, the γδ T‐cell receptor, major histocompatibility complex (MHC) class I complex and class II antigens, and complement membrane attack complex (MAC) were examined. The distribution and relative proportions of T cells and T‐cell subsets, B cells, macrophages, and eosinophils were determined at perivascular, perimysial, endomysial, and fascial sites of accumulation. At all sites, T cells were predominant, CD8+ cells outnumbered CD4+ cells 6‐ to 20‐fold, and between 60 and 80% of T cells were activated. B cells and eosinophils each accounted for less than 3% of inflammatory cells. Very few cells expressed either the γδ T‐cell receptor or natural killer cell markers. As in dermatomyositis (DM), MHC class I antigen complex expression was increased on many structurally normal muscle fibers, but in contrast to DM, microvascular MAC deposits were not a feature of EMS. The findings implicate a cellular immune response directed against a connective tissue component in EMS.
Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig
Authors: Brod Staley A. , al‐Sabbagh Ahmad , Sobel Raymond A. , Hafler David A. , Weiner Howard L.
Published: January 2005

Oral administration of proteins is a long‐recognized method of inducing antigen‐specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed‐type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti–myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis.
Benefits of monitoring plasma levodopa in Parkinson's disease patients with drug‐induced chorea
Authors: Sage Jacob I. , Mark Margery H. , McHale Denise M. , Sonsalla Patricia K. , Vitagliano Dawn
Published: January 2005

We studied the temporal patterns of chorea and plasma levodopa profiles in 30 patients with Parkinson's disease whose motor fluctuations were difficult to characterize and treat on the basis of observation alone. We were able to determine whether chorea was associated with high levodopa concentrations or low levodopa concentrations or both. We found the following patterns of levodopa‐associated chorea: chorea due to inadequate levodopa levels, chorea due to biphasic levodopa absorption, chorea associated with either rapid or slow levodopa absorption, and chorea due to long‐duration levodopa absorption mimicking a sustained‐release preparation. Seven patients benefited after their dosing schedules were rearranged as a result of information gained from monitoring. We conclude that any patient with levodopa‐associated chorea who cannot be regulated on the basis of observation alone should be studied with simultaneous plasma levodopa measurements and clinical monitoring to detect an unusual plasma levodopa pattern that may be improved by adjustment of dosing schedule.
Epilepsy surgery in the posterior cortex
Authors: Blume Warren T. , Whiting Sharon E. , Girvin John P.
Published: January 2005

Fourteen (74%) of 19 patients obtained a significant reduction in seizures after posterior corticectomy; 6 (32%) were seizure‐free over a median follow‐up of 3.7 years (range, 1 to 14 years). Surgery included limited resections of the occipital lobe in 16 patients, posterior temporal region in 11, and posterior portion of parietal lobe in 7. Surgical failure related to probable multiple areas of epileptogenesis (4 patients), or limited resections (2 patients) to preserve visual fields (2 patients) and to avoid dyslexia (1 patient). Of 14 patients without a complete hemianopia preoperatively, 6 (43%) developed a new or increased visual field deficit, 2 (14%) of which were hemianopia. Four (36%) of 11 occipital lobe resections resulted in a new or increased visual field deficit: quadrantanopia in 3 and hemianopia in 1. Visual phenomena were the most common initial ictal symptoms, occurring in 13 (68%) of the 19 patients. Twelve patients had complex partial seizures: in 2, always without warning; in 7, always following an aura, usually visual; and in 3 patients, with or without warning. Scalp electroencephalography identified the origin of most recorded seizures in 12 (63%) of the 19 patients. A principal interictal spike focus appeared in 15 patients (79%), and always correlated with the epileptogenic lobe as defined by scalp and/or subdural‐recorded seizures (14 patients) or by clinical analysis and computed tomography (1 patient).
Motor responses after transcranial electrical stimulation of cerebral hemispheres with a degenerated pyramidal tract
Authors: Fries Wolfgang , Danek Adrian , Witt Thomas N.
Published: January 2005

Motor responses were evoked in the thenar muscles by transcranial electrical cortex stimulation in 5 stroke patients with an isolated lacuna in the internal capsule, in whom wallerian degeneration of the pyramidal tract was demonstrated in vivo. Suprathreshold stimulation of the affected hemisphere elicited bilateral motor responses; whereas, stimulation at identical intensities of the undamaged hemisphere yielded strictly unilateral responses in the contralateral hand, like the responses of all normal control subjects. Focused magnetic brain stimulation was performed in 1 patient and gave identical results. Because muscular excitability to cortical stimulation is preserved in spite of pyramidal tract disruption, other pathways must bypass the lesion. Because of the bilaterality of responses, we suggest polysynaptic corticoreticulospinal connections.
Neocortical damage during HIV infection
Authors: Wiley Clayton A. , Masliah Eliezer , Morey Mitchel , Lemere Cindy , DeTeresa Richard , Grafe Marjorie , Hansen Lawrence , Terry Robert
Published: January 2005

Clinical and pathologicals evidence of subcortical central nervous system (CNS) damage is observed commonly in patients with human immunodeficiency virus (HIV) encephalitis. Whether other CNS regions are also affected has not been well studied. We report neocortical damage in patients with HIV encephalitis. Using quantitative techniques, we demonstrate statistically significant thinning of the neocortex, with a loss of large cortical neurons. Qualitative and quantitative assessments of neocortical neuropil reveal a loss of synaptic density and vacuolation of dendritic processes. Failure to demonstrate an association of these changes with the presence of HIV antigens suggests that neocortical damage may be an indirect effect of HIV infection of the CNS.
Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow
Authors: Bhatt Mohit H. , Snow Barry J. , Martin W. R. Wayne , Pate Brain D. , Ruth Thomas J. , Calne Donald B.
Published: January 2005

We performed sequential positron emission tomography scans with 6‐[18F]fluoro‐L‐dopa in 9 patients with idiopathic parkinsonism and 7 age‐matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.
Magnetic resonance imaging–based volume studies in temporal lobe epilepsy: Pathological correlations
Authors: Cascino Gregory D. , Jack Clifford R. , Parisi Joseph E. , Sharbrough Frank W. , Hirschorn Kathryn A. , Meyer Frederic B. , Marsh W. Richard , O'Brien Peter C.
Published: January 2005

We performed a prospective study correlating magnetic resonance imaging volume measurements of the hippocampal formation with histopathology in 24 patients with intractable partial epilepsy who subsequently underwent an anterior temporal lobectomy for their seizure disorder. Patients with mass lesions verified pathologically were excluded from this study. In 71% of patients, quantitative hippocampal formation atrophy correctly lateralized the temporal lobe of seizure origin; in 29%, the volume study was indeterminant. The severity of the pathological alterations in the hippocampus correlated with the hippocampal formation volume determination. Mesial temporal sclerosis was identified in the surgically excised temporal lobe in 15 patients. The magnetic resonance imaging volume studies indicated hippocampal atrophy in the temporal lobe resected in 14 of the 15 patients. Magnetic resonance imaging‐based volume measurements of the hippocampal formation increase the diagnostic yield of magnetic resonance imaging scanning in patients with intractable partial epilepsy related to mesial temporal sclerosis.
Increased lymphocyte beta‐adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28− suppressor cell
Authors: Karaszewski Joseph W. , Reder Anthony T. , Anlar Banu , Kim Woo Chan , Arnason Barry G. W.
Published: January 2005

Beta‐adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28−) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta‐adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 ± 0.3 fmol/106 cells versus a density of 5.1 ± 0.7 fmol/106 cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 ± 0.4 fmol/106 cells in control subjects and 0.9 ± 0.3 fmol/106 cells in the patients. Monocytes displayed beta‐adrenergic receptor densities of 2.6 ± 0.4 fmol/106 cells in normal individuals and 2.7 ± 0.4 fmol/106 cells in the patient group. CD8 lymphocyte beta‐adrenergic receptor densities in patients with relapsing‐remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin‐2 (IL‐2) similarly. However, IL‐2 treatment increased beta‐adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS. We conclude that decreased sympathetic skin responses, increased CD8+, CD28− cell beta‐adrenergic receptor density, impaired suppressor cell function, and increased IL‐2 production may be interrelated, and that increased beta‐adrenergic receptor density is confined to the chronic progressive form of MS.
Serum interleukin‐2 concentrations in Guillain‐Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: Comparison with other neurological diseases of presumed immunopathogenesis
Authors: Hartung Hans‐Peter , Reiners Karlheinz , Schmidt Beate , Stoll Guido , Toyka Klaus V.
Published: January 2005

Serum concentrations of the cytokine interleukin‐2 (IL‐2) were quantitated by enzyme‐linked immunosorbent assay in 42 patients with Guillain‐Barré syndrome, 15 patients with chronic idiopathic demyelinating polyradiculoneuropathy, 37 patients with other neuropathies, 54 patients with other noninflammatory, nondemyelinating neurological disorders, and 26 healthy control subjects. We found markedly increased serum levels of IL‐2 in patients with Guillain‐Barré syndrome and to a much lesser extent, in patients with chronic idiopathic demyelinating polyradiculoneuropathy. Increased serum concentrations of IL‐2 in patients with Guillain‐Barré syndrome returned to normal in parallel with recovery from the disease. These findings suggest ongoing T‐cell proliferation in patients with Guillain‐Barré syndrome and some patients with chronic idiopathic demyelinating polyradiculoneuropathy. IL‐2 levels were also raised in patients with active multiple sclerosis, myasthenia gravis, and herpes simplex encephalitis, and some patients with polymyositis, invoking T cells in the pathogenesis of these diseases.
Auditory evoked magnetic fields after ischemic brain lesions
Authors: Mäkelä J. P. , Hari R. , Valanne L. , Ahonen A.
Published: January 2005

Auditory evoked magnetic fields to noise/square‐wave sequences, presented once every 2.2 seconds, were recorded in 8 patients who had ischemic lesions in the auditory cortex or in its vicinity. In 2 patients with large temporoparietal lesions, the magnetic 100‐msec deflection (N100m) was absent over the damaged side. In 1 patient with a large but less deep frontotemporal lesion, a small N100m could be discerned on the defective side. Frontal lesions or small lesions in the vicinity of the supratemporal plane had no effect on N100m. Auditory evoked magnetic field recordings may be useful in clinical studies of auditory cortical functions.
Phosphorus magnetic resonance spectroscopy (31P MRS) in neuromuscular disorders
Authors: Argov Zohar , Bank William J.
Published: January 2005

Phosphorus magnetic resonance spectroscopy monitors muscle energy metabolism by recording the ratio of phosphocreatine to inorganic phosphate at rest, during exercise, and during recovery from exercise. In mitochondrial diseases, abnormalities may appear during some or all these phases. Low phosphocreatine—inorganic phosphate ratios at rest are not disease‐specific, but can be increased by drug therapy in several myopathies. Phosphorus magnetic resonance spectroscopy can also record intracellular pH and thus identify disorders of glycogen metabolism in which the production of lactic acid is blocked during ischemic exercise. The measurements of accumulated sugar phosphate intermediates further delineate glycolytic muscle defects. Myophosphorylase deficiency responds to intravenous glucose administration with improved exercise bioenergetics, but no such response is seen in phosphofructokinase deficiency. The muscular dystrophies show no specific bioenergetic abnormality; however, elevation of phospholipids metabolites and phosphodiesters was detected in some cases. While phosphorus magnetic resonance spectroscopy remains primarily a research tool in metabolic myopathies, it will be clinically useful in identifying new therapies and monitoring their effects in a variety of neuromuscular disorders.
Neuritic pathology and dementia in alzheimer's disease
Authors: McKee A. C. , Kosik K. S. , Kowall N. W.
Published: January 2005

Previous studies of Alzheimer's disease (AD) have correlated the severity of dementia with either the number of senile plaques or neurofibrillary tangles. We used antibodies raised against amyloid β/A4 protein of senile plaque cores and tau protein as well as thioflavine S and the Campbell‐Switzer modification of the Hicks silver method to examine the hippocampal formation and five neocortical regions from 22 nondemented elderly control subjects and 34 demented patients with cerebral senile plaques and neurofibrillary tangles, without complicating disease processes. Ten control subjects (46%) had no β/A4 protein deposition. Twelve control subjects (54%) had widespread β/A4 protein deposition but no neocortical neuritic pathology. Of the 34 patients with AD‐type changes, 27 (79%) had widespread senile plaques and neurofibrillary tangles, while 7 (21%) had neocortical senile plaques with few neurofibrillary tangles. All demented patients had widespread β/A4 protein deposition and neocortical tau‐immunoreactive, Hicks silver‐positive dystrophic neurites. The neurites were found both free in the neuropil as well as surrounding senile plaques. Quantitative analysis showed that dystrophic neurites were significantly increased in patients with AD compared with control subjects and the number of dystrophic neurites and neurofibrillary tangles correlated with the clinical severity of dementia. Widespread cerebral β/A4 protein deposition may be necessary but by itself is insufficient for the development of dementia in AD.
Impaired critical flicker frequency in recovered optic neuritis
Authors: Jacobson Daniel M. , Olson Kurt A.
Published: January 2005

Thirteen patients with optic neuritis who recovered normal visual acuity and kinetic perimetry all showed impairment of foveal critical flicker frequency, a psychophysical test of visual temporal resolution. Because the magnocellular visual system demonstrates higher temporal resolution than the parvocellular system, this finding implicates involvement of axonal projections of magnocellular retinal ganglion cells in recovered optic neuritis.
Mitochondrial oxidative phosphorylation defects in parkinson's disease
Authors: Shoffner John M. , Watts Ray L. , Juncos Jorge L. , Torroni Antonio , Wallace Douglas C.
Published: January 2005

Parkinson's disease has been associated with defects in oxidative phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays were compared to the 5 to 95% confidence intervals from 16 control subjects. Four patients had complex I defects, whereas 1 patient had a complex IV defect. A genetic basis for Parkinson's disease was suggested by the presence of affected relatives of 2 patients with Parkinson's disease. Known pathological mitochondrial DNA mutations (insertion‐deletions or point mutations) were not found. We conclude that Parkinson's disease is a systemic disorder of Oxphos, probably of a complex genetic etiology. Premature cell death in the nigrostriatal dopamine pathway could be due to energetic impairment and accentuated free radical generation caused by an Oxphos defect.
Anterior callosotomy in the treatment of medically intractable epilepsies: A study of 43 patients with a mean follow‐up of 39 months
Authors: Oguni Hirokazu , Olivier André , Andermann Frederick , Comair Joseph
Published: January 2005

We studied the effectiveness of anterior callosotomy in 43 patients whose follow‐up period averaged 39 months. These patients had intractable generalized seizures, characterized by a combination of seizure patterns, most frequently drop attacks with generalized tonic‐clonic, generalized tonic, and absence seizures. Overall, drop attacks were the most frequent (31/43 or 72%) and the most disabling seizure pattern (27/43 or 63%); they were also the most likely to benefit from anterior callosotomy (70%). Patients with lateralized changes tended to have a better result than did those without lateralization, but patients with synchronous and symmetrical spike and wave discharges also benefited. The preoperative intelligence quotient and the etiological factors were not predictors of outcome. There was a correlation between the extent of section and the results; patients with section of the anterior two thirds had a better result, compared with those who had section of the anterior half.