bluuebunny/crossref_metadata_2025 huggingface dataset:
Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system
Authors: Goadsby P. J. , Edvinsson L. , Ekman R.
Published: January 2005

The trigeminal ganglion was activated, in humans by thermocoagulation as part of the treatment of trigeminal neuralgia and in cats by electrical stimulation, and blood samples were taken from the external jugular vein for estimates of plasma levels of substance P and calcitonin gene‐related peptide (CGRP). In those patients who were noted at the time of coagulation to have flushed there were marked elevations of the local (cranial) levels of both peptides. However, in the nonflushing patients no changes in the peptide levels were observed. Parallel experiments in the cat revealed that the levels of substance P—like and CGRP‐like immunoreactivity were increased during electrical stimulation of the trigeminal ganglion. The observation of elevation of substance P—like and CGRP‐like immunoreactivity after activation of the nociceptive afferent system of the head provides new insights into a putative role of peptides in the pathophysiology of migraine and cluster headache, and suggests new areas of possible therapeutic intervention.
Cortisol induction by poly ICLC: Implications for clinical trials of interferon
Authors: Bever Christopher T. , McFarland Henry F. , Levy Hilton B. , McFarlin Dale E.
Published: January 2005

Because interferon injections have recently been reported to induce cortisol in cancer patients, we retrospectively reviewed cortisol levels obtained during a preliminary trial of the interferon inducer polyriboinosinic polyribocytidylic acid in poly‐L‐lysine and carboxymethylcellulose (poly ICLC) in multiple sclerosis patients to determine if significant cortisol induction occurred. Analysis of data from 51 poly ICLC infusions in 6 men and 4 women showed elevated cortisol levels 4 to 16 hours after infusion, with hematological changes consistent with steroid effect. The highest cortisol levels observed were in 2 patients who improved during the treatment period, but there was no clear relationship between cortisol levels and clinical outcome in the group as a whole.
Infantile gaucher's disease: A case with neuronal storage
Authors: Grafe Marjorie , Thomas Carol , Schneider Jerry , Katz Barrett , Wiley Clayton
Published: January 2005

The brain of a 17‐month‐old boy with infantile Gaucher's disease and oculomotor apraxia was studied by light and electron microscopy. Light microscopic examination showed large perivascular accumulations of Gaucher's cells in frontal lobe white matter, severe neuronal loss in the calcarine cortex and dentate nucleus of the cerebellum, and neuronophagia and microglial nodules in the brainstem. Electron microscopy demonstrated intraneuronal cytoplasmic inclusions containing twisted tubules characteristic of Gaucher's disease in both the oculomotor nucleus and a random sample of cortex.
Alz‐50 Antibody recognizes alzheimer‐related neuronal changes
Authors: Hyman B. T. , Van Hoesen G. W. , Wolozin B. L. , Davies P. , Kromer L. J. , Damasio A. R.
Published: January 2005

Alz‐50 is a monoclonal antibody directed against an antigen present in Alzheimer's disease. Unlike conventional pathological stains that reveal only neurons with neurofibrillary tangles (NFTs), Alz‐50 recognizes neurons that contain NFTs and additional neurons that do not. Our investigation of the topographical distribution of both NFT‐containing and non‐NFT‐containing neurons recognized by Alz‐50 reveals that they are both found primarily in certain cytoarchitectural areas and lamina that have been established as consistent sites for NFT pathology. Some of the neurons recognized by Alz‐50 appear histopathologically normal. We suggest that Alz‐50 recognizes an antigen in neurons that both precedes and accompanies NFT formation. Thus, it may mark a point early in cellular pathology before irreversible cytoskeletal and degenerative changes occur.
Monoclonal antibody analysis of mononuclear cells in myopathies. V: Identification and quantitation of T8+ cytotoxic and T8+ suppressor cells
Authors: Arahata Kiichi , Engel Andrew G.
Published: January 2005

In polymyositis (PM) and inclusion body myositis (IBM), but not in dermatomyositis there is evidence of cell‐mediated cytotoxicity: T8+ cells accompanied by macrophages focally surround, invade, and destroy nonnecrotic muscle fibers. However, the T8 marker appears on both cytotoxic (Tc) and suppressor (Ts) cells. The Leu‐15 marker appears on Ts but not on Tc cells, but it also appears on macrophages and on some killer/natural killer cells. To obviate this problem, the T8, Leu‐15, and Leu‐7 markers were demonstrated by sequential paired immunofluorescence in single cryostat sections. Using this approach, we reliably differentiated for the first time between Tc and Ts cells in tissue sections. Six cell phenotypes were identified: T8+Leu‐15− Leu‐7− Tc cells, T8+Leu‐15+Leu‐7− Ts cells, three types of Leu‐7+ killer/natural killer cells, and T8−Leu‐15+Leu‐7− macrophages. Muscle specimens from 5 patients with PM and 5 with IBM were studied. In each case, 6 nonnecrotic muscle fibers focally surrounded and invaded by mononuclear cells were selected randomly. A total of 2,022 mononuclear cells were analyzed, 870 from patients with PM and 1,152 from those with IBM. When counts of the identified cell phenotypes in individual patients were pooled, there were four times as many T8+Leu‐15−Leu‐7− Ts cells as T8+Leu‐15+Leu‐7− Ts cells in either PM or IBM samples. However, when the relative frequencies of the Tc and Ts cells were examined in individual patients, the Tc cells tended to become more abundant, and the Ts cells correspondingly less abundant, with the duration of symptoms. These data indicate that the T8+ Tc cell is the predominant phenotype in cell‐mediated cytotoxicity in PM and IBM.
Atlantoaxial subluxation in psoriatic arthropathy
Authors: Kaplan Jerry G. , Rosenberg Richard S. , DeSouza Trevor , Post Kalmon D. , Freilich Mark D. , Salamon Oscar , Lantos George , Reinitz Elizabeth
Published: January 2005

Symptomatic atlantoaxial dislocation occurs rarely in psoriatic arthropathy and has previously been reported only as a late complication in this disorder. We report severe upward axial dislocation and acquired basilar impression as a presenting manifestation of psoriatic arthropathy. Magnetic resonance imaging is useful in evaluating this condition.
The metabolic anatomy of paraneoplastic cerebellar degeneration
Authors: Anderson N. E. , Posner J. B. , Sidtis J. J. , Moeller J. R. , Strother S. C. , Dhawan V. , Rottenberg D. A.
Published: January 2005

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration {PCD}) were evaluated using neuropsychological tests and 18F‐fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia, rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reduction in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a “reverse cerebellar diaschisis”.
Spinocerebellar ataxia: Variable age of onset and linkage to human leukocyte antigen in a large kindred
Authors: Zoghbi Huda Y. , Pollack Marilyn S. , Lyons Leslie A. , Ferrell Robert E. , Daiger Stephen P. , Beaudet Arthur L.
Published: January 2005

We studied a seven‐generation kindred with autosomal dominant spinocerebellar ataxia (SCA) to assess linkage relationships to multiple human leukocyte antigen (HLA) loci on the short arm of chromosome 6. Age at onset, clinical features, and course of the disease are described. Although the mean age of onset was 34 years in this family, in 6 of 41 affected individuals onset was below 15 years of age and was accompanied by the unique clinical features of mental retardation and rapid progression of disease. Linkage studies were performed on 93 individuals, and the results show strong evidence for linkage of the SCA locus to the HLA loci. A maximum logarithm of the odds score of 5.83 was found at a recombination fraction of 0.12. This is the first documentation of childhood onset in the HLA‐linked form of SCA.
Influence of neuronal location on antigenic properties of neurofibrillary tangles
Authors: Tabaton Massimo , Perry George , Autilio‐Gambetti Lucila , Manetto Valeria , Gambetti Pierluigi
Published: January 2005

We quantitatively assessed the antigenic properties of the neurofibrillary tangles (NFT) located in neurons of the tegmental nuclei of the pontine raphe in progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). These properties were then compared with those of NFT of AD located in hippocampal neurons. Antibodies known to react with cortical NFT of AD were used to stain sections from PSP, AD, and control cases. The reaction with the straight filaments of NET of PSP and with the paired helical filaments of pontine NFT of AD was ascertained by immunoelectron microscopy. The results show that, despite the ultrastructural difference, straight filaments in NFT of PSP and paired helical filaments in NFT of AD share antigenic properties when they are located in the same neuronal population. In contrast, paired helical filaments located in the cerebral cortex are antigenically different from those in pontine nuclei. Location, more than structure, may play a role as determinant of antigenic properties in straight filaments of PSP and paired helical filaments of AD.
Toluene abuse causes diffuse central nervous system white matter changes
Authors: Rosenberg Neil L. , Kleinschmidt‐DeMasters B. K. , Davis Kathleen A. , Dreisbach James N. , Hormes Joseph T. , Filley Christopher M.
Published: January 2005

We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2‐weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill‐defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene‐induced metabolic changes in myelin.
Chronic unilateral optic neuropathy: A magnetic resonance study
Authors: Eidelberg D. , Newton M. R. , Johnson G. , MaCmanus D. G. , McDonald W. I. , Miller D. H. , Halliday A. M. , Moseley I. F. , Heng G. S. , Wright J.
Published: January 2005

We studied the clinical, electrophysiological, and magnetic resonance imaging (MRI) features of 20 patients with chronic unilateral optic neuropathy (CUON): progressive unilateral visual failure lasting a minimum of 6 months. The patients, 10 male and 10 female, ranged in age from 12 to 77 years (mean 44) and had a mean duration of symptoms of 22 months. All had signs of optic nerve dysfunction. Each patient was studied with MRI using a short TI inversion recovery (STIR) sequence to delineate the optic nerve from surrounding orbital tissue. Three distinct groups of patients with CUON were identified using MRI. In the first group (8/20) the optic nerve was compressed by an extrinsic mass, whereas in the second group (5/20) CUON resulted from an intrinsic tumor of the optic nerve or sheath. In both groups STIR sequences compared favorably with computed tomography in identifying mass lesions. MRI was superior in delineating distortion of the optic nerve by mass or tumor extension beyond the orbit. In the third group (7/20) no mass was evident on MRI. However, STIR sequences revealed altered signal (long Tl) in clinically symptomatic nerves. In 4 of the patients T2‐weighted cerebral MRI disclosed periventricular lesions suggestive of disseminated white matter disease. We conclude that MRI complements clinical and electrophysiological testing in the assessment of CUON.
Borrelia burgdorferi—specific and autoreactive T‐cell lines from cerebrospinal fluid in lyme radiculomyelitis
Authors: Martin Roland , Ortlauf Johannes , Sticht‐Groh Veronika , Bogdahn Ulrich , Goldmann Shraga F. , Mertens Hans Georg
Published: January 2005

In 3 patients with Lyme radiculomyelitis, cellular immune reactions of cerebrospinal fluid (CSF) lymphocytes were analyzed. Phenotypic analysis of CSF cells demonstrated that the majority were T cells (CD3 +) of the helper/inducer subset (CD4 +). These T cells were directly expanded from the CSF by limiting dilution. A total of 505 T‐cell lines were tested for Borrelia burgdorferi (Bb)—specific proliferation and also partly tested for reactivity to a panel of central and peripheral nervous system antigens. Proliferative assays revealed 33 of them to be Bb specific, 16 to be specific for myelin basic protein, 16 to be specific for peripheral myelin, 1 to be specific for cardiolipin, and 2 to be specific for galactocerebrosides. The antigen‐specific proliferation was restricted by autologous human leukocyte antigen (HLA) class II molecules. The majority of CSF‐derived T‐cell lines stained positively for CD3, CD4, and HLA class II antigens and negatively for CD8 (cytotoxic/suppressor subset). One T‐cell line provided help for the production of specific IgG by autologous B cells and secreted gamma‐interferon upon stimulation with Bb antigen in the presence of autologous antigen‐presenting cells. These data show that in patients with severe neurological manifestations of late Lyme disease, not only Bb‐specific T‐cell lines but also T cells reactive to central or peripheral nervous system autoantigens can be found.
Infantile and fetal globoid cell leukodystrophy: Analysis of galactosylceramide and galactosylsphingosine
Authors: Kobayashi Takuro , Goto Ikuo , Yamanaka Tatsuhiro , Suzuki Yoshiyuki , Nakano Takeshi , Suzuki Kunihiko
Published: January 2005

Galactosylceramide and galactosylsphingosine (psychosine) were assayed in tissues from infants and fetuses with globoid cell leukodystrophy (GLD). Galactosylceramide concentrations were not increased in nervous tissues or other organs. Using a sensitive assay method, we found galactosylsphingosine accumulations in GLD tissues, both infantile and fetal, which suggests that GLD is a generalized galactosylsphingosine storage disease. High galactosylsphingosine levels were observed in the brain, spinal cord, and sciatic nerve of infants with GLD and in the spinal cord of a fetus with GLD, where lesions characteristic to GLD were noted. In tissues without morphological changes, such as somatic organs and the brain in fetal GLD, galactosylsphingosine concentrations were low. These results suggest that a close relationship exists between galactosylsphingosine accumulation and the pathogenesis of GLD. The finding that galactosylsphingosine, but not galactosylceramide, accumulates in the tissue of GLD can be explained by our previous observation that galactosylceramide, but not galactosylsphingosine, is readily hydrolyzed by an intact galactosylceramidase II, which is genetically distinct from galactosylceramidase I.
The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy
Authors: Jensen Morten S. , Yaari Yoel
Published: January 2005

In studies of focal epilepsy it is frequently assumed that the interictal spike is the elementary form of epileptic activity and that seizure, or ictal, episodes evolve by temporal summation and spatial expansion of interictal paroxysms. We examined this hypothesis in an in vitro model of acute focal epilepsy produced by perfusing rat hippocampal slices with solutions containing moderately elevated concentrations of K+. Some of the preparations treated in this way displayed recurring electrical seizures in the CA1 field. Each seizure episode typically evolved by a seemingly smooth progression of brief interictal bursts into sustained ictal discharge. However, exposure of preparations showing electrical seizures to blockers of synaptic transmission or to cholinergic agonists abolished interictal spiking in all hippocampal fields but did not impede the initiation of ictal episodes in area CA1. Likewise, severing the connections between areas CA3 and CA1 abolished interictal spiking in area CA1 without disrupting the initiation of seizures in this region. These data clearly show that in this model, focal seizures arise independent of interictal spikes and through different cellular mechanisms. While interictal electrogenesis requires chemical synaptic excitation, ictal episodes can be initiated and maintained by nonsynaptic neuronal interactions.
Selective sparing of NADPH‐diaphorase neurons in neonatal hypoxia‐ischemia
Authors: Ferriero Donna M. , Arcavi Lidia J. , Sagar Stephen M. , McIntosh Tracy K. , Simon Roger P.
Published: January 2005

Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia‐ischemia, lesions of the cortex and striatum were induced in 7‐day‐old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinu‐cleotide phosphate diaphorase (NADPH‐d) activity. Concentrations of the neuropeptides somatostatin and neuropeptide Y, which colocalize in neurons containing NADPH‐d, were unaffected in the areas of ischemic damage. The same pattern of injury with sparing of NADPH‐d‐reactive neurons was reproduced by focal microinfusion of the excitotoxin quinolinic acid, an endogenous N‐methyl‐d‐aspartate (NMDA) agonist, into the striatum. These results support the hypothesis that neonatal hypoxic‐ischemic injury is mediated through excitatory transmitters acting at the NMDA receptor and that the NADPH‐d‐reactive neurons in the neonate are resistant to excitotoxic damage. This pattern of cell vulnerability is unique to the developing striatum and may relate to the distinct pathological appearance of the basal ganglia that follows neonatal asphyxia.
Findings in muscle in complex I (NADH coenzyme Q reductase) deficiency
Authors: Koga Yasutoshi , Nonaka Ikuya , Kobayashi Masanori , Tojyo Megumu , Nihei Kenji
Published: January 2005

Thirteen of 15 patients with complex I deficiency had the multisystemic form, with strokelike episodes and other symptoms that fulfilled the diagnostic requirements for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), and 2 had only muscle fatigability and weakness, having the purely myopathic form. In the multisystemic form, 12 patients had ragged‐red fibers. All multisystemic patients had myopathic histochemical abnormalities that consisted of mild to moderate variation in fiber size (13), disorganized intermyofibrillar networks (12), type 2 fiber atrophy (10), and an increased number of type 2C fibers (9). Five of 13 multisystemic patients had Decemberreased cytochromec oxidase (CCO) activity in extrafusal fibers, with sparing of intrafusal muscle fibers. In the myopathic form, pathological findings were similar to those in the multisystemic form. In addition to complex I and NADH dehydrogenase activities being Decemberreased, the CCO activity was significantly Decemberreased (less than 50% of control value) in 8 patients, especially when the disease was in its advanced stages, suggesting that CCO enzyme might be secondarily affected as the disease progresses.
Interleukin‐2 levels in serum and cerebrospinal fluid of multiple sclerosis patients
Authors: Gallo P. , Piccinno M. , Pagni S. , Tavolato B.
Published: January 2005

A sensitive enzyme‐linked immunosorbent assay method was employed to measure interleukin‐2 (IL‐2) levels in cerebrospinal fluid (CSF) and sera from 30 patients with multiple sclerosis (MS) and 8 patients with other neurological diseases. Detectable levels of IL‐2 were found in 6 sera and 9 CSF samples of 21 patients with acute relapse of MS. However, only 3 patients showed measurable IL‐2 both in CSF and in serum. IL‐2 was not detected in specimens from 9 patients with chronic progressive MS, whereas high levels were found in 2 CSF samples from patients with aSeptembertic meningitis. Our data suggest that systemic activation of a T‐cell population is present in some MS patients; moreover, an active immune mechanism involving IL‐2 production takes place within the central nervous system.
Gray‐matter degeneration in presenile alzheimer's disease
Authors: Prohovnik Isak , Smith Gwenn , Sackeim Harold A. , Mayeux Richard , Stern Yaakov
Published: January 2005

Previous comparisons between presenile Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) did not control for disease severity and duration. In the current study, 18 patients with each diagnosis were matched for disease duration, cognitive dysfunction, and behavioral symptoms (using the modified Mini‐Mental Status [mMMS] examination and the Blessed Dementia Rating Scale [BDRS]). Regional cerebral blood flow (rCBF) was quantified by the 133xenon inhalation technique, and several indices of tissue perfusion were examined. The two variables of primary interest were relative gray‐matter weight and a gray‐matter perfusion index, the initial slope index. Presenile onset was associated with loss of gray‐matter relative weight (35% in presenile patients versus 39% in senile patients and healthy control subjects, p = 0.006), with neither perfusion nor disease severity differences between the two dementia samples. This loss of gray matter was significantly related to both severity and duration of disease in the patients with presenile AD, but not in patients with SDAT. These findings lend support to previous suggestions of greater degenerative process in presenile AD and confirm the need to examine and control age of onset in future investigations of AD. Further, correlation analysis suggests greater proportion of common variance among clinical and physiological indices in presenile AD.
The open opercular sign: Diagnosis and significance
Authors: Tatum William O. , Coker Steven B. , Ghobrial Mona , Abd‐Allah Shamel
Published: January 2005

Four children with varying clinical manifestations, but with the unifying feature of severe developmental delay, had bilateral enlargement of the sylvian fissure confirmed by magnetic resonance imaging (MRI). Subsequently, we examined 125 consecutive MRI scans of the heads of pediatric patients, looking for this insular exposure, and did not find it. Pathological correlation in 1 child revealed arhinencephaly and abnormal gyral formation; another is known to have migrational abnormalities. We suggest that the open operculum is a sign of arrested development and is associated with other anomalies and a poor prognosis.
Activated suppressor cell function in severely disabled patients with multiple sclerosis
Authors: Antel J. P. , Freedman M. S. , Brodovsky S. , Francis G. S. , Duquette P.
Published: January 2005

Defective suppressor cell function has previously been demonstrated in patients with multiple sclerosis (MS) with progressive disease and moderate degrees of disability. In the present study activated suppressor cell function was assessed in patients with documented progressive disease who, at the time of study, had experienced severe disability (Kurtzke score ≥ 6.5) for at least 2 years. We found that mean suppressor levels were significantly increased in this patient group compared with the suppressor levels in the MS patient group with progressive disease but only moderate disability (Kurtzke score of ≤ 6.0 within 2 years of study) (59 ± 8% vs 19 ± 7%, respectively, p < 0.01). The mean value in the latter group was significantly reduced compared with the mean value for normal control subjects (47 ± 4%, p < 0.01), a finding consistent with previous reports. The results of this study indicate that suppressor cell function, as measured by our assay system, need not be defective in MS patients who have become severely disabled from the progressive form of the disease. Whether the patients who are now severely disabled from progressive MS passed through a phase of disease associated with the same suppressor defects as found in the progressive patients currently with moderate disability will remain speculative until long‐term longitudinal studies are performed.
Impaired human leukocyte antigen–restricted measles virus–specific cytotoxic T‐cell response in subacute sclerosing panencephalitis
Authors: Dhib‐Jalbut Suhayl , Jacobson Steven , McFarlin Dale E. , McFarland Henry F.
Published: January 2005

The capacity of peripheral blood lymphocytes to proliferate in response to measles virus and to generate measles virus–specific cytotoxic T lymphocytes (CTL) was examined in 4 patients with subacute sclerosing panencephalitis (SSPE). The lymphoproliferative response to measles virus was obtainable in the 4 SSPE patients. In contrast, the CTL response to measles virus was reduced in 3 of the 4 SSPE patients. This defect appeared to be in the generation of the measles virus–specific CTLs, since measles virus–infected target cells from the patients could be lysed by human leukocyte antigen–matched peripheral blood lymphocytes from healthy individuals. The SSPE patients with reduced measles virus CTL response had a normal ability to generate mumps virus, influenza virus, or alloantigen–specific CTLs. The lysis of measles virus–infected targets that was observed with these SSPE patients could be reduced by depleting the effectors of natural killer cells or by performing cold target blocking with K562 cells, indicating that the lysis of the measles virus–infected targets was probably mediated by natural killer cells. These results demonstrate a reduction in the cell‐mediated immune response to measles virus as measured by the generation of measles virus–specific CTLs in 3 of the 4 SSPE patients studied. This defect could relate to the persistence of measles virus in these patients.
Viral infectious complementary‐DNA studies may identify nonviral genes critical to central nervous system disease
Authors: Ohara Yoshiro , Roos Raymond P.
Published: January 2005

A major interest of modern science and medicine is the delineation of genes that cause disease. In the case of cancer, the study of viral oncogenic genes led to the recognition of similar human genes that play an important role in this disease. In an analogous fashion, the identification of viral genes important in central nervous system disease may lead to the recognition of related cellular genes that are important in nonviral central nervous system disease. New molecular techniques now provide tools for identification of pathogenic viral genes and elucidation of mechanisms of disease production. Positive‐strand RNA viruses such as picornaviruses provide an especially attractive model system for studies of central nervous system disease–producing genes. A limitation in molecular studies of these viruses has resulted from an inability to use restriction enzymes, since these enzymes are active against DNA and not RNA. This limitation has recently been overcome with the preparation of infectious picornavirus complementary‐DNA. This review highlights the importance of infectious complementary‐DNA in pathogenesis studies and provides a glimpse of the impact of such studies on neurology.
Peripheral nerve pathological findings in familial amyloid polyneuropathy: A correlative study of proximal sciatic nerve and sural nerve lesions
Authors: Hanyu Norinao , Ikeda Shu‐Ichi , Nakadai Akira , Yanagisawa Nobuo , Powell Henry C.
Published: January 2005

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased‐fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a spaceoccupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.
Multicenter trial of naloxone in alzheimer's disease
Authors: Henderson V. W. , Roberts E. , Wimer C. , Bardolph E. L. , Chui H. C. , Damasio A. R. , Eslinger P. J. , Folstein M. F. , Schneider L. S. , Teng E. L. , Tune L. E. , Weiner L. P. , Whitehouse P. J.
Published: January 2005

In a double‐blind, placebo‐controlled, crossover study of intravenously administered naloxone hydrochloride, 54 subjects with clinically ascertained Alzheimer's disease tested at three university centers showed no significant improvement in neuropsychological performance after 1‐mg or 10‐mg doses; 15 patients at 1 center were similarly unimproved after receiving 30 mg naloxone (single blind). Findings fail to support claims that naloxone monotherapy ameliorates cognitive impairments of Alzheimer's disease.
Vascular involvement in mitochondrial myopathy
Authors: Sakuta Ryoichi , Nonaka Ikuya
Published: January 2005

Electron microscopic examination of muscle specimens taken at biopsy in 6 patients with complex I deficiency and 1 patient with an unknown primary chemical defect who had the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) revealed striking abnormalities in blood vessels in 5. Abnormalities consisted of an increased number of enlarged mitochondria with complicated cristae in the pericytes of capillaries, endothelial cells, and smooth muscle cells of the small arteries, including terminal arterioles and precapillary sphincters, predominantly in smooth muscle cells. On statistical analysis, the number of mitochondria and the ratio of mitochondrial area to the total area of the smooth muscle cells were increased approximately tenfold (p < 0.001). Although stroke‐like episodes were not present, similar mitochondrial abnormalities in blood vessels were found in 1 patient who had the encephalomyopathic form of complex IV deficiency and in 2 patients in whom the primary chemical defects could not be clearly defined. Such abnormalities in small arteries might be responsible for the occasional occurrence of transient cerebral ischemia causing stroke‐like episodes and progressive mental deterioration.
A quantitative investigation of the substantia nigra in Huntington's disease
Authors: Oyanagi Kiyomitsu , Takeda Shigeki , Takahashi Hitoshi , Ohama Eisaku , Ikuta Fusahiro
Published: January 2005

To elucidate the quantitative and topographical changes of neurons in the substantia nigra in Huntington's disease (HD), sections from 4 HD patients and 8 age‐matched control subjects were stained with cresyl violet and the numbers and localization of pigmented and nonpigmented neurons in the substantia nigra were examined. This study revealed a decrease of about 40° (p < 0.01 or p < 0.05) in neuronal number and a shrinkage of both pigmented and nonpigmented neurons in the substantia nigra in HD. Pigmented neuron number was decreased markedly in the ventral cell group. Loss of the neurons occurred in the medial and lateral thirds, but relative sparing of the neurons was seen in the central part of the substantia nigra. In contrast, loss of nonpigmented neurons was relatively uniform in the substantia nigra although it was more severe in the central part. We conclude that a primary neuronal degeneration occurs in the substantia nigra in HD.
Lipid‐containing cells in brains of normal and hypoxic infant monkeys: A quantitative and ultrastructural study
Authors: Goddard‐Finegold Jan , Sloper John J. , Esiri Margaret M.
Published: January 2005

The signficance of lipid‐containing cells found at autopsy in the white matter of infant brains is controversial, particularly with respect to their postulated role as markers of the “sudden infant death syndrome.” To determine whether such cells are indicative of prior nonlethal hypoxic insult, we quantitated them in the brains of control infant monkeys and in two groups of infant monkeys that were subjected to 30 minutes of hypoxic insult. One group consisting of monkeys that died less than 48 hours after the hypoxia, and the other of those that survived 7 to 13 days following the insult. The quantification of lipid‐containing cells was undertaken in frozen brain sections stained with Oil red O; sections of brains from 4 perfusion‐fixed animals were evaluated by electron microscopy.

Lipid‐containing cells were found in the corpus callosum, in the septum, and in periventricular white matter in both posthypoxic and control animals. There was a relationship between numbers of lipid‐containing cells and the age of the animal; animal with large numbers were less than 28 days old. Decreases in numbers of lipid‐containing cells correlated with advancing myelination as well as with age. Electron microscopic evaluation revealed lipid droplets in the cytoplasm of cells with irregularly shaped nuclei, densely clumped chromatin, occasional microtubules, and narrow cytoplasmic processes.

We suggest that lipid‐containing cells in the white matter of the brains of infants are related to age and to maturational factors and, in the absence of other pathologic signs, are not related to prior hypoxic injury.
Benign childhood epilepsy with occipital paroxysms: A 15‐year prospective study
Authors: Panayiotopoulos Chrysostomos P.
Published: January 2005

Eighteen of 418 children who had onset of epilepsy before the age of 13 years showed clinical and electroencephalographic evidence of benign childhood epilepsy with occipital paroxysms. They represented one‐fifth of all benign age‐ and localization‐related idiopathic epilepsies seen. Some patients were followed as long as 15 years. There was a preponderance in females and peak age at onset of epilepsy was 5 years. In 16 children, the seizures were infrequent and sometimes prolonged and consisted mainly of tonic deviation of the eyes and vomiting, often with evolution to unilateral or generalized convulsions. Seizures were only nocturnal in 11 and nocturnal and diurnal in another 5 children. Prognosis was excellent; 5 children had only one fit. Remission usually occurred 1 to 2 years after onset and no seizures occurred after the age of 12 years. The remaining 2 children had frequent diurnal episodes consisting of visual hallucinations, postictal headache, and occasional nocturnal hemiconvulsions. Their prognosis was less favorable. Electroencephalographic abnormalities in all 18 patients consisted of repetitive spike and slow‐wave discharges confined to the occipital regions and attenuated when the eyes were open. These outlasted clinical remission for many years, sometimes up to the age of 16. Fixation‐off sensitivity was demonstrated frequently. Based on these findings, a unifying definition for benign childhood epilepsy with occipital paroxysms is proposed.
Magnetic resonance imaging morphology of the corpus callosum in monozygotic twins
Authors: Oppenheim Jeffrey S. , Skerry John E. , Gazzaniga Michael S.
Published: January 2005

Recent reports describe wide variations in the size and shape of the human corpus callosum. To investigate genetic influences on this variability, magnetic resonance images from 5 pairs of monozygotic twins and 10 unrelated control subjects were analyzed. Measurements of size and shape revealed greater similarity in twin pairs than in randomly paired controls. The results are consistent with the view that the anatomy of the corpus callosum, while clearly influenced by nongenetic factors, is under considerable genetic control.
Aberrant guanosine triphosphate–beta‐tubulin interaction in Alzheimer's disease
Authors: Khatoon Sabiha , Campbell Susan R. , Haley Boyd E. , Slevin John T.
Published: January 2005

Guanosine triphosphate (GTP) is an absolute requirement for tubulin polymerization in situ. The nucleotide photoaffinity probe 8‐azidoguanosine 5′‐triphosphate (8N3GTP) has been shown to be a biological mimic of GRP in this system and, also, an effective active site probe of the exchangeable GRP binding site. Using [32P]8N3GTP we demonstrate that the exchangeable GTP site of the beta subunit of tubulin is available to added guanine nucleotide in normal aged brain homogenates, whereas it is variably unavailable in Alzheimer's diseased brain. Inability of 8N3GTP to photolabel beta tubulin appears to be associated with neurofibrillary tangle density. These results support the hypothesis that microtubule formation is abnormal in brains affected by Alzheimer's disease.
Chronic progressive multiple sclerosis: Serial magnetic resonance brain imaging over six months
Authors: Koopmans R. A. , Li D. K. B. , Oger J. J. F. , Kastrukoff L. F. , Jardine C. , Costley L. , Hall S. , Grochowski E. W. , Paty D. W.
Published: January 2005

Eight patients in the chronic progressive stage of multiple sclerosis were studied prospectively with magnetic resonance imaging of the head and neurological examination every 2 weeks for 6 months. There were no clinical relapses and disability ratings did not change between the start and completion of the study. Despite the clinical inactivity, a total of 86 active events (new, reappearing, or enlarging lesions) were identified by magnetic resonance imaging over the 6 months, with 50 (51) of 98 follow‐up scans showing evidence of one or more active lesions. New and changing lesions were indistinguishable in appearance, distribution, and temporal pattern from those previously seen in patients who had relapsing and remitting multiple sclerosis. However, as noted previously, the patients in the chronic progressive stage had many more confluent lesions than did the group in relapse. These results strongly suggest that the frequently observed clinical evolution of multiple sclerosis into a chronic progressive course is not accompanied by a fundamental change in the disease process. In fact the chronic progressive stage seems associated with more active changes demonstrated by scans than does relapsing and remitting multiple sclerosis. This study also confirms our previous experience that serial magnetic resonance imaging is much more sensitive than clinical examination in detecting disease activity in multiple sclerosis.
Isolation of herpes simplex virus type 1 during first attack of multiple sclerosis
Authors: BergstOum Tomas , Andersen Oluf , Vahlne Anders
Published: January 2005

Herpes simplex virus type 1 was isolated from the cerebrospinal fluid of a patient during the first attack of multiple sclerosis. This is the first virus to be isolated from the central nervous system of a living patient with MS. The virus was identified as herpes simplex virus type 1 by restriction endonuclease analysis and by an enzytme immunoassay using monoclonal antibodies. Antibodies against type 1 but not type 2 were detected in consecutive samples of serum and cerebrospinal fluid. The patient has since entered a progressive phase of multiple sclerosis. The isolated type 1 strain might be of pathogenetic relevance to the development of multiple sclerosis in this patient.
Increased replication of HTLV‐I in HTLV‐I–associated myelopathy
Authors: Yoshida Mitsuaki , Osame Mitsuhiro , Kawai Hisaomi , Toita Masami , Kuwasaki Nanako , Nishida Yoshihiko , Hiraki Yukako , Takahashi Kouichi , Nomura Koichiro , Sonoda Shunro , Eiraku Nobutaka , Ijichi Shinji , Usuku Koichiro
Published: January 2005

To estimate the replication of the human T‐cell leukemia virus type I (HTLV‐I) in patients with HTLV‐I‐associated myelopathy (HAM), or tropical spastic paraparesis (TSP), HTLV‐I DNA integrated into lymphocyte genomes was analyzed by Southern blot hybridization. HTLV‐I DNA was detected in 125 (82%) of 153 patients and most showed random integration. This incidence was much higher than the 29% found in asymtopmatic carriers. Therefore, HAM/TSP development is associated with a high level of HTLV‐I replication. In addition, lymphocytes from 3 patients with HAM/TSP showed monoclonal integration of HTLV‐I DNA, indicating adult T‐cell leukemia.
Cisplatin‐induced Neurotoxicity with Seizures in Frogs
Authors: Blisard Karen S. , Harrington Deborah A.
Published: January 2005

Cis‐diamminedichloroplatinum II (cisplatin) given by injection to adult frogs (Rana pipiens) reslted in tonic‐clonic seizures 3 to 5 weeks later. The seizures could be induced multiple times; the animals appeared entirely normal between seizures. In the spinal cord there was vacuolation in the anterior grey horns. Ultrastructurally, the vacuoles consisted of swollen astrocytic processes in the neuropil and around neurons. Generalized edema with swelling of perivascular astrocyte foot processes was not seen. Systemic administration of cisplatin to frogs results in neurotoxicity with seizures and astrocytic swelling in the spinal cord.
Human cytotoxic T‐cell recognition of a synthetic peptide of myelin basic protein
Authors: Richert John R. , Robinson Eve D. , Deibler Gladys E. , Martenson Russell E. , Dragovic Ljubo J. , Kies Marian W.
Published: January 2005

Previous studies with a panel of myelin basic protein (MBP)–specific human T‐cell clones suggested a clustering of epitopes in the middle and at the C terminus of the molecule. The current study demonstrates that 19 of 40 clones recognize a synthetic peptide corresponding to residues 152 to 170 of the human MBP molecule and that 9 clones recognize a synthetic peptide corresponding to residues 86 to 105. Myelin basic protein–specific cytotoxic activity was restricted to the clones that recognized peptide 152–170, and this peptide served as a preferential cytotoxic T‐cell target when attached to an autologous B‐cell line. The specificity of MBP‐directed cytotoxic activity appears to be much more restricted than the specificity demonstrated for proliferative activity.
Cardiogenic brain embolism and lupus anticoagulant
Authors: Young Seymour M. , Fisher Marc , Sigsbee Ann , Errichetti Annmarie
Published: January 2005

The lupus anticoagulant, an acquired immunoglobulin associated with an increased tendency for thrombosis, has been linked to the occrence of cerebral ischemia presumably related to in situ thrombosis. Cardioembolic cerebral ischemic events have rarely been reported. We encountered 2 patients with focal cerebral ischemia, substantial mitral valvular masses, and a circulating lupus anticoagulant. In each, diagnostic evaluation supported a cardioembolic etiology. These findings illustrate the need for evaluating patients with cerebral ischemic events for a cardioembolic source when a circulating lupus anticoagulant is present.
Tropical spastic paraparesis: A model of virus‐induced, cytotoxic T‐cell–mediated demyelination?
Authors: Moore G. R. Wayne , Traugott Ute , Scheinberg Labe C. , Raine Cedric S.
Published: January 2005

Tropical spastic paraparesis is a neurological disorder that is most commonly seen in certain tropical (mainly Caribbean) areas and that presents as a progressive spastic paraparesis and urinary dysfunction. Recent studies have revealed an association between tropical spastic paraparesis and human T‐cell lymphotropic virus type I (HTLV‐I) infection. We report the results of a detailed morphological and immunocytochemical study of a patient with tropical spastic paraparesis. Lesions were restricted to the spinal cord and optic nerve, where demyelination, inflammation, and fiber loss were common features. Lymphocytes were seen closely applied to nerve fibers within which were changes resembling those seen in myelinated central nervous system cultures exposed to cytokines. Immunocyctochemically, HTLV‐I p19 core protein and a predominance of CD8+ (suppressor/cytotoxic) T cells and expression of class I major histocompatibility antigen were demonstrated in spinal cord lesions. It is postulated that cytotoxic T cells, either directly or via cytokines, induce lysis of the myelin sheath and subsequently the axon, resulting in a mixed picture of demyelination and axonal loss with secondary tractal degeneration. Despite this destruction, extensive remyelination was evident within affected areas of spinal cord.
Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis
Authors: Franciotta D. M. , Grimaldi L. M. E. , Martino G. V. , Piccolo G. , Bergamaschi R. , Citterio A. , D'Eril G. V. Melzi
Published: January 2005

We measured levels of alpha–tumor necrosis factor (α‐TNF) in cerebrospinal fluid and serum samples from 50 drug‐free patients with multiple sclerosis, 25 patients with other neurological diseases, 27 patients with non‐neurological diseases, and 10 normal subjects. The most elevated levels of α‐TNF were found in patients with inflammatory or autoimmune diseases. Comparable serum levels of α‐TNF were detected in normal control subjects, patients with multiple sclerosis, and patients with degenerative neurological diseases. In patients with multiple sclerosis, α‐TNF levels were also unrelated to time elapsed between the occurrence of clinical exacerbation and the time of sample collection. Only 3 patients with chronic progressive multiple sclerosis had detectable α‐TNF in the cerebrospinal fluid. Our data do not support a role for elevated levels of circulating α‐TNF in the maintenance of the disease. However, we cannot rule out the possibility that a transient elevation of a α‐TNF triggers the cellular events leading to demyelination in multiple sclerosis.