bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid pleocytosis following simple, complex partial, and generalized tonic‐clonic seizures
Authors: Devinsky Orrin , Nadi N. Suzan , Theodore William H. , Porter Roger J.
Published: January 2005

We observed postictal pleocytosis in 7 of 62 cerebrospinal fluid specimens obtained from 27 patients with epilepsy. Each patient had a known seizure disorder; none had any other cause for the pleocytosis. The maximum number of leukocytes was 12/mm3; the maximum number of erythrocytes was 190/mm3. Postictal pleocytosis was more common in samples obtained within 12 hours of the last seizure. Although previous studies have emphasized that pleocytosis is more common after repetitive generalized tonic‐clonic seizures, we found increased leukocyte counts in cerebrospinal fluid after single simple, complex partial, or generalized tonic‐clonic seizures.
Congenital odontoid aplasia and posterior circulation stroke in childhood
Authors: Phillips Peter C. , Lorentsen Kevin J. , Shropshire Lowry C. , Ahn Hyo S.
Published: January 2005

Head trauma and vigorous physical activity were followed by delayed‐onset posterior circulation stroke in a 5‐year‐old boy with odontoid aplasia and C1‐C2 subluxation. Angiography demonstrated vertebral artery narrowing and occlusion of the left anterior‐inferior cerebellar and posterior cerebral arteries. Odontoid aplasia and other atlantoaxial dislocations are treatable causes of posterior circulation insufficiency in childhood; these defects may be overlooked without appropriate radiographic study of the cervical spine using flexionextension views.
Stroke associated with obstructive sleep apnea in a child with sickle cell anemia
Authors: Robertson Patricia L. , Aldrich Michael S. , Hanash Samir M. , Goldstein Gary W.
Published: January 2005

We describe a child with sickle cell anemia and multiple ischemic infarctions who was found to have severe obstructive sleep apnea and hypoxemia, secondary to adenotonsillar enlargement. The apnea‐associated hypoxemia likely contributed to the development of the strokes in this child. Moreover, because stroke in patients with sickle cell anemia, and maximal tonsillar enlargement (the most common cause of obstructive apnea in children) both have peak incidence at the same age (6–7 years), obstructive sleep apnea may be an important factor in the development of stroke in other children with sickle cell anemia.
Human antiidiotypic antibody against opiate receptors
Authors: Roy Benjamin F. , Bowen Wayne D. , Frazier James S. , Rose John W. , McFarland Henry F. , McFarlin Dale E. , Murphy Dennis L. , Morihisa John M.
Published: January 2005

Sera containing antibodies toβ‐endorphin from 2 patients with major depressive disorder were shown to have antiidiotypic antibodies that specifically inhibited reactivity between anti‐β‐endorphin IgG andβ‐endorphin. Autologous and homologous antiidiotypic anti‐anti‐β‐endorphin IgG antibodies were isolated by affinity chromatography. The purified antiidiotypic antibody did not bindβ‐endorphin but competed with [125I]β‐endorphin for rat brain opiate receptors. Normal IgG that was similarly treated had negligible competitive effects. The antibody bound to the membrane preparation; such binding was inhibited by opiate receptor ligands. Binding of the antiidiotype to a 60,000‐dalton protein from rat brain was detected by Western immunoblot analysis. This protein corresponds in molecular weight to proteins proposed to be components of opiate receptors. These findings imply that immune reactivity to neuropeptides could contribute to psychiatric impairment.
Expression of nerve growth factor receptor in human peripheral neuropathies
Authors: Sobue Gen , Yasuda Takeshi , Mitsuma Terunori , Ross Alonzo H. , Pleasure David
Published: January 2005

Nerve growth factor (NGF) receptors in human sural nerve biopsies were detected immunohistochemically using a monoclonal anti‐human NGF receptor antibody. NGF receptors were not visualized within the endoneurium of normal adult nerves but were readily demonstrable within the endoneurium of nerves undergoing active axonal degeneration. Immunostaining of adjacent sections for S‐100β protein, a specific Schwann cell Marchker, suggested that Schwann cells expressed the NGF receptors induced by axonal degeneration. Residual Schwann cells in nerves in which axons were completely depleted also expressed NGF receptors. NGF receptors were not detected in relation to thinly myelinated regenerating axons, nor were they detected in the endoneurium of nerves that had undergone segmental demyelination and remyelination. The increased expression of NGF receptors in human axonal neuropathies may contribute to regeneration by NGF‐responsive neurons in these disorders.
Two cases of Wernicke's encephalopathy in children: An underdiagnosed complication of poor nutrition
Authors: Seear Michael D. , Norman Marchgaret G.
Published: January 2005

We describe the occurrence of Wernicke's encephalopathy in two children in whom the diagnosis was not suspected during life. Postmortem examination showed changes characteristic of the disease. This preventable and treatable condition is probably underdiagnosed in poorly nourished, nonalcoholic patients of all ages.
Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases
Authors: Helkala Eeva‐Liisa , Laulumaa Veikko , Soininen Hilkka , Riekkinen Paavo J.
Published: January 2005

Alzheimer's and Parkinson's diseases are associated with cognitive impairment, although the pattern of cognitive dysfunction is not identical. We investigated the recall and recognition memory of 18 patients with idiopathic Parkinson's disease (PD) and of 32 patients with probable Alzheimer' disease (AD). In the list‐learning test using Buschke's selective reminding method, PD patients showed superior delayed recognition memory capability compared to AD patients, whereas immediate recall did not differ in the two groups. In the delayed story recall, PD patients were also able to benefit from rehearsal and probe more than AD patients. The results suggest that PD patients are able to bind information better into long‐term storage than are AD patients. This may be due to better function in PD of the entorhinal cortex and hippocampus.
Loss of evoked potentials during spinal surgery due to spinal cord hemorrhage
Authors: Shukla R. , Docherty T. B. , Jackson R. K. , Weller R. O. , Sedgwick E. M.
Published: January 2005

The cortical somatosensory evoked potential (September) disappeared during corrective spinal surgery in a patient with muscular dystrophy. The patient died 18 hours after surgery. Autopsy revealed an intramedullary hemorrhage 4 mm in diameter in the posterior horn of the cervical spinal cord. Microscopically, hypoxic neurons were seen adjacent to the hemorrhagic area, implying that the lesion was at least 6 hours old. The hemorrhage corresponded to the loss of Septembers and confirms that spinal cord monitoring can detect such lesions.
Cerebrospinal fluid homovanillic acid and parkinsonism in Huntington's disease
Authors: Kurlan Roger , Goldblatt David , Zaczek Robert , Jeffries Keith , Irvine Carrie , Coyle Joseptemberh , Shoulson Ira
Published: January 2005

In Huntington's disease (HD), normal or Decemberreased levels of homovanillic acid (HVA) in cerebrospinal fluid (CSF) have been reported but have not been analyzed with respect to severity of parkinsonism, which in certain cases may be a predominant feature of the illness. We obtained CSF by lumbar puncture from four groups of nonmedicated subjects: (1) those with HD in the earliest stages of illness (n = 51), (2) those with parkinsonism, including idiopathic (n = 10) and atypical forms (n = 4), (3) those with nonparkinsonian movement disorders (n = 19), and (4) normal volunteers (n = 4). HVA was determined by high‐pressure liquid chromatography with electrochemical detection, and motor signs were assessed in standardized fashion. The parkinsonian group had reduced levels of CSF HVA, but the other groups showed no significant differences. For those with HD, no correlation was found between HVA level and severity of parkinsonism, and there were no differences in HVA level between those subjects with (n = 14) of without (n = 37) prominent parkinsonism or between subjects whose age at illness onset was 30 years or less (n = 16) and those whose age at onset was over 30 (n = 35). Our findings indicate that in early, untreated HD, CSF HVA is in the normal range and does not correlate with the severity of parkinsonism. This observation supports neuropathological findings suggesting that parkinsonian features in HD are largely related to the loss of postsynaptic striatal dopamine receptors rather than to presynaptic nigral degeneration.
The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis
Authors: Plaitakis Andreas , Constantakakis Evangelos , Smith Jeffrey
Published: January 2005

Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly Decemberreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
Encephalitis among cree children in northern Quebec
Authors: Black Deborah N. , Watters Gordon V. , Andermann Eva , Dumont Charles , Kabay Michel E. , Kaplan Paige , Meagher‐Villemure Kathleen , Michaud Jean , O'gorman Gus , Reece Elena , Tsoukas Christos , Wainberg Marchk A.
Published: January 2005

We report a neurological disease among Cree Indian children in a northern Quebec village. The disease manifests as severe mental retardation, cerebral atrophy with white matter changes and calcifications, and systemic immunological abnormalities. Eleven cases are known in five families. The familial incidence of cases and the high degree of parental consanguinity suggest a genetic contribution. We propose that this entity may be caused by an unusual viral infection in a genetically vulnerable host.
Ataxia—ocular motor aprilaxia: A syndrome mimicking ataxia‐telangiectasia
Authors: Aicardi Jean , Barbosa Célia , Andermann Eva , Andermann Frederick , Morcos Rami , Ghanem Qais , Fukuyama Yukio , Awaya Yutaka , Moe Paul
Published: January 2005

We report 14 patients with a slowly progressive syndrome featuring ataxia, choreoathetosis, and ocular motor Aprilaxia in both the horizontal and vertical planes. Although the neurological signs were indistinguishable from those of ataxia‐telangiectasia, the onset tended to be later and none of the patients had evidence of multisystemic involvement. Specifically, there was no tendency to frequent infections, and immunoglobulins, α‐fetoprotein, T‐ and B‐lymphocyte Marchkers, and chromosomes 7 and 14 were normal in all tested patients. The simultaneous absence of telangiectasias and of other nonneurological manifestations made ataxia‐telangiectasia an unlikely diagnosis. We suggest that these patients suffer from an unusual type of spinocerebellar degeneration. This syndrome has been observed in different populations from three continents, with a genetic pattern suggesting recessive autosomal inheritance.
The glutamate antagonist MK‐801 reduces focal ischemic brain damage in the rat
Authors: Park C. K. , Nehls D. G. , Graham D. I. , Teasdale G. M. , McCulloch J.
Published: January 2005

Excessive activation of the N‐methyl‐D‐aspartate (NMDA) subtype of glutamate receptor has been implicated in the sequence of neurochemical events that results in irreversible neuronal damage in cerebral ischemia. The effects of the NMDA antagonist (+) ‐5‐methyl‐10,ll‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine maleate (MK‐801) upon the amount of ischemic brain damage has been assessed quantitatively in the lightly anesthetized rat. Focal cerebral ischemia was produced by the permanent occlusion of one middle cerebral artery (MCA), and the animals were killed 3 hours after the arterial occlusion. MK‐801 (0.5 mg/kg) was administered intravenously either 30 minutes prior to MCA occlusion or 30 minutes after the induction of ischemia. Pretreatment with MK‐801 reduced the volume of ischemic damage both in the cerebral cortex (by 38% compared with untreated rats with MCA occlusion; p < 0.01) and in the caudate nucleus (by 18% compared with controls; p < 0.05). Treatment with MK‐801, initiated 30 minutes after MCA occlusion, reduced the volume of ischemic damage in the cerebral cortex (by 52% compared with controls; p < 0.01). The volume of ischemic damage in the caudate nucleus was minimally influenced by MK‐801 treatment initiated after MCA occlusion. The antiischemic effects of MK‐801 were readily demonstrable despite the hypotension that MK‐801 induced in rats anesthetized with halothane (0.5%), nitrous oxide (70%), and oxygen (30%). The potency of MK‐801 in reducing ischemic brain damage, even when administered after the induction of ischemia, highlights the potential use of NMDA receptor antagonists for the treatment of focal cerebral ischemia in humans.
Absence status epilepticus with computed tomographic brain changes following metrizamide myelography
Authors: Obeid Tahir , Yaqub Basim , Panayiotopoulos Chrysostomos , Al‐Jasser Saleh , Shabaan Azzam , Hawass Nour El‐Din
Published: January 2005

Absence status epilepticus following metrizamide myelography was associated with computed tomographic scan evidence of a high concentration of the dye in brain gray matter. We suggest that absence status epilepticus is due to the direct effect of metrizamide on the cortex and that this clinically treatable condition may have escaped diagnosis in previous reports.
Dementia, parkinsonism, and motor neuron disease: Neurochemical and neuropathological correlates
Authors: Gilbert Joseptemberh J. , Kish Stephen J. , Chang Li‐Jan , Morito Caryl , Shannak Kathleen , Hornykiewicz Oleh
Published: January 2005

The neurochemical Marchkers for the major neurotransmitter systems were measured in the brain of a patient who died with a dementia‐parkinsonism‐motor neuron disease (DPMN) syndrome complex. Moderate neuronal loss in the substantia nigra, spongiform changes in the frontal cortex, and moderate anterior horn cell loss throughout the spinal cord were observed. A severe nigrostriatal dopamine deficiency provides the basis for the observed parkinsonian features. The dementia is unexplained.
Magnetic resonance imaging–based brain morphometry: Development and application to normal subjects
Authors: Filipek Pauline A. , Kennedy David N. , Caviness Verne S. , Rossnick Susan L. , Spraggins Thomas A. , Starewicz Piotr M.
Published: January 2005

A semiautomated computerized method of in vivo morphometric analysis that is based upon high‐resolution three‐dimensional magnetic resonance imaging has been developed. This morphometric method is efficient and is of greater analytical precision than any other morphometric method currently applied to living human tissue. Including error inherent in image data acquisition, the aggregate error of the methodology, as estimated by the phantom studies, ranges from 4.5 to 9.6%, with incremental error above 4.5% a function of magnetic resonance slice thickness. This method was applied to magnetic resonance scans of 7 normal volunteers. The derived volumes of whole brain and of individual substructures were closely concordant with previously published volumes of normal fresh (unfixed) brains obtained post mortem. This morphometric methodology is potentially applicable to any structure or lesion that can be visualized by magnetic resonance imaging.
Hypoxia‐sensitive hyperexcitability of the intramuscular nerve axons in isaacs' syndrome
Authors: Oda Kenichiro , Fukushima Noriko , Shibasaki Hiroshi , Ohnishi Akio
Published: January 2005

A case of Isaacs' syndrome with Trousseau's phenomenon is reported. Myokymia, pseudomyotonia (difficulty relaxing after forceful contraction), and ischemia‐induced carpal spasm (Trousseau's phenomenon) were not abolished by nerve block distal to the cuff or by intravenous infusion of calcium. Inhalation of oxygen suppressed the pseudomyotonia and Trousseau's phenomenon, but myokymia persisted. Phenytoin abolished all types of abnormal discharges. The morphological abnormality in biopsied short peroneal muscle consisted of intraterminal and ultraterminal sprouting. We postulate that the trigger zone for abnormal discharge in our case is in the distal segment of the intramuscular nerve axon, including the nerve terminal. Hypoxia‐sensitive hyperexcitability of the axon membrane might be responsible for the generation of pseudomyotonia and Trousseau's phenomenon, although the mechanism underlying myokymia remains unknown.
A controlled clinical trial of baclofen as protective therapy in early huntington's disease
Authors: Shoulson Ira , Odoroff Charles , Oakes David , Behr Jill , Goldblatt David , Caine Eric , Kennedy Judith , Miller Charlyne , Bamford Kathryn , Rubin Allen , Plumb Sandra , Kurlan Roger
Published: January 2005

We carried out a controlled clinical trial to examine the potential of baclofen to slow the functional decline of patients with early Huntington's disease (HD). The basis of the trial was: (1) the hypothesis that excitatory amino acid neurotransmission mediates the neuronal degeneration of HD, (2) preclinical evidence that baclofen retards corticostriatal release of glutamate and aspartate, and (3) reports that baclofen produces short‐term clinical benefits in some HD patients. Sixty patients with early HD were randomized to chronic baclofen, 60 mg/day, or placebo treatments and followed systematically for up to 42 months. Total functional capacity was not favorably influenced by baclofen treatment. Factors that contributed, although nonsignificantly, to a more rapid rate of total functional capacity decline included younger age (< 35 years), earlier stage (stage I) of illness, paternal inheritance of the HD gene, and baclofen treatment. Our patients declined at a pace slower than that observed in other prospective studies, a finding likely due to selection criteria, avoidance of neuroleptic therapy, and strong psychosocial support.
Inclusion body myositis: The mumps virus hypothesis
Authors: Nishino Hiroshi , Engel Andrew G. , Rima Burt K.
Published: January 2005

The resemblance of the filamentous inclusions in inclusion body myositis (IBM) to mumps virus nucleoproteins and the report of immunoreactivity of the inclusions for mumps virus antigens have implicated the mumps virus in the etiology of IBM. We tested the mumps virus hypothesis by in‐situ hybridization with a cDNA probe specific for the mumps virus nucleocapsid gene, and immunocytochemically with antibodies against “soluble” and “viral” mumps antigens. The tests were performed on muscle specimens (IBM, 20; acid maltase deficiency, 4; chloroquine myopathy, 2; nonweak control subjects, 5) and mumps virus–infected and uninfected HEp‐2 cells. The in‐situ hybridization study showed a strong specific signal in the infected HEp‐2 cells but no specific signal in IBM, other myopathies, or nonweak control subjects. The immunocytochemical study showed specific binding of the antimumps antibodies to the infected HEp‐2 cells but demonstrated only nonspecific binding of these antibodies around rimmed vacuoles in IBM, acid maltase deficiency, and chloroquine myopathy. These studies cast doubt on the mumps hypothesis of IBM.
High‐dose leucovorin reverses acute high‐dose methotrexate neurotoxicity in the rat
Authors: Phillips Peter C. , Thaler H. Tzvi , Allen Jeffrey C. , Rottenberg David A.
Published: January 2005

Intravenous high‐dose methotrexate (HD‐MTX) reduces cerebral glucose metabolism and produces behavioral abnormalities and electroencephalographic slowing in an animal model of acute HD‐MTX neurotoxicity and in cancer patients undergoing HD‐MTX chemotherapy. We used our model of HD‐MTX neurotoxicity in the rat to determine if leucovorin (5‐formyltetrahydrofolate) reduces this neurotoxicity, and extended our characterization of this model to identify regional as well as global HD‐MTX treatment effects and to investigate HD‐MTX‐induced alterations in regional brain pH. Intravenous high‐dose leucovorin reversed the HD‐MTX‐induced decrease in cerebral glucose metabolism and associated behavioral and electroencephalographic abnormalities in the rat, but low‐dose leucovorin was ineffective. The major effect of HD‐MTX on cerebral glucose metabolism was a global reduction; however, smaller region‐specific treatment effects were identified in auditory, thalamic, and white matter structures. HD‐MTX did not alter regiona brain pH. These findings suggest a potential clinical role for high‐dose leucovorin in severe or prolonged acute HD‐MTX neurotoxicity and provide an important justification for the role of positron emission tomography in the early detection of clinical HD‐MTX neurotoxicity.
N‐methyl‐D‐aspartate antagonists: Ready for clinical trial in brain ischemia?
Authors: Albers Gregory W. , Goldberg Mark P. , Choi Dennis W.
Published: January 2005

Antagonists of the N‐methyl‐D‐aspartate (NMDA) subclass of glutamate receptors may offer a new approach for the treatment of ischemic brain injury. This strategy is supported by a well‐developed scientific foundation and encouraging results in a variety of in vivo and in vitro experimental models. Several specific antagonists, including MK‐801, dextrorphan, dextromethorphan, and ketamine, have already been used at low doses in humans for other indications and are potential candidates for Phase I clinical trials.
Quantitation of cerebral atrophy in preclinical and end‐stage alzheimer's disease
Authors: de la Monte Suzanne M.
Published: January 2005

Morphometric analysis of standardized gross cerebral slices from 16 patients with end‐stage Alzheimer's disease (AD), 14 controls without neuropathological lesions or neurological disease, and 4 neurologically intact nondemented patients with histopathological lesions of AD was used to measure cross‐sectional areas of cerebral cortex, white matter, subcortical nuclei, and the ventricular system. In AD, there was global cerebral atrophy of both cortex and white matter, selective atrophy of the amygdala and hippocampus, and ex vacuo hydrocephalus. In addition, in half the cases of AD, white matter atrophy was associated with overt histopathological evidence of patchy rarefaction of fibers and gliosis. Patients with preclinical AD had prominent and selective shrinkage of white matter comparable to that observed in AD, yet their cortical areas were normal. These observations suggest that white matter degeneration is an intrinsic component of AD. Moreover, its presence in preclinical AD where cortical atrophy is not evident indicates that cytoskeletal abnormalities associated with axonal degeneration may precede and perhaps cause the cortical atrophy observed in clinically manifested AD.
Normalization of short‐chain acylcoenzyme a dehydrogenase after riboflavin treatment in a girl with multiple acylcoenzyme a dehydrogenase—deficient myopathy
Authors: Didonato Stefano , Gellera Cinzia , Peluchetti Dionisio , Uziel Graziella , Antonelli Antonella , Lus Giacomo , Rimoldi Marco
Published: January 2005

A 12‐year‐old girl was shown to have carnitine‐deficient lipid storage myopathy and organic aciduria compatible with multiple acylcoenzyme A (acyl‐CoA) dehydrogenase deficiency. In muscle mitochondria, activities of both short‐chain acyl‐CoA dehydrogenase (SCAD) and medium‐chain acyl‐CoA dehydrogenase (MCAD) were 35% of normal. Antibodies against purified SCAD, MCAD, and electron‐transfer flavoprotein were used for detection of cross‐reacting material (CRM) in the patient's mitochondria. Western blot analysis showed absence of SCAD‐CRM, reduced amounts of MCAD‐CRM, and normal amounts of electron‐transfer flavoprotein‐CRM. The patient, who was unresponsive to treatment with oral carnitine, improved dramatically with daily administration of 100 mg oral riboflavin. Increase in muscle bulk and strength and resolution of the organic aciduria were associated with normalization of SCAD activity and “reappearance” of SCAD‐CRM. In contrast, both MCAD activity and MCAD‐CRM remained lower than normal. These results suggest that in some patients with multiple acyl‐CoA dehydrogenase deficiency riboflavin supplementation may be effective in restoring the activity of SCAD, and possibly of other mitochondrial flavin‐dependent enzymes.
Neurological autoimmune disease and the trimolecular complex of T‐lymphocytes
Authors: Hohlfeld Reinhard
Published: January 2005

T‐lymphocytes recognize antigen in a trimolecular complex: The T‐cell receptor binds to a processed fragment of antigen that itself is bound to a major histocompatibility complex (MHC) molecule on the surface of an antigen‐presenting cell. The trimolecular complex controls antigen‐specific T‐cell activation in normal and abnormal immune reactions. Recent progress in myasthenia gravis (MG) and experimental autoimmune encephalomyelitis (EAE) exemplifies this, leading to the following conclusions: (1) Autoimmune T cells may act by interfering with immunoregulation (as in MG) or by directly mediating autoimmune damage (as in EAE), or both. (2) In both diseases, the autoimmune T cells are clonally heterogeneous but recognize only a limited number of epitopes on the autoantigen (acetylcholine receptor in MG; myelin basic protein in EAE). Many of these epitopes can be defined as short peptide fragments of antigen, bound to a particular type of MHC molecule. (3) The MHC determines which peptides are recognized by autoimmune T cells in a given patient or inbred animal strain. (4) The discovery of the limited repertoire of autoimmune T cells has allowed considerable progress in the immunotherapy of EAE, using either monoclonal antibodies or cytotoxic T cells directed against clonotypic determinants on the autoaggressive T cells. (5) One obstacle to this approach in human disease is the polymorphism of the MHC in the species and the commensurate heterogeneity of autoimmune T cells.
Bilateral central macrogyria: Epilepsy, pseudobulbar palsy, and mental retardation—a recognizable neuronal migration disorder
Authors: Kuzniecky Ruben , Andermann Frederick , Tampieri Donatella , Melanson Denis , Olivier Andre , Leppik I.
Published: January 2005

The neuronal migration disorders comprise several morphological entities that are recognizable during life using current imaging techniques. We studied 4 patients who had a characteristic bilateral central rolandic and sylvian macrogyria. The patients had pseudobulbar palsy with oromotor incoordination and developmental delay and were mildly retarded. Minor seizures developed between the ages of 8 and 9 years. Subsequently, atonic drop attacks became the predominant epileptic pattern. Epileptogenic electrographic abnormalities were secondary generalized or multifocal. The lesions were detected by computed tomography and magnetic resonance imaging in all patients. Bilateral symmetrical areas of thick cortex surrounding a large sulcus were seen. This syndrome consists of specific clinical, imaging, electroencephalographic, and epileptic features. It can be suspected clinically and confirmed by imaging studies. Callosotomy in two patients helped the intractable seizures.
Middle cerebral artery pial territory infarcts: A study of the lausanne stroke registry
Authors: Bogousslavsky Julien , van Melle Guy , Regli Franco
Published: January 2005

Using a standard protocol (Doppler ultrasonography, electrocardiography, brain computed tomography, and in selected cases angiography, echocardiography, and Holter monitoring) we studied the clinical characteristics and etiological factors in 380 patients with first stroke who had a corresponding infarct limited to the territory of the pial branches of the middle cerebral artery (MCA) on computed tomography. The presumed cause of infarction was large‐artery disease (≥ 50% carotid artery or MCA stenosis or occlusion) in one‐third of the patients and cardioembolism in one‐fourth of the patients. Half of 230 patients undergoing angiography showed evidence for distal occlusions suggesting artery‐to‐artery or cardiac emboli. Severe heart disease and potential cardiac sources of embolism were more common in patients with infarcts in the territory of the posterior (inferior) division of MCA than in patients with infarcts in the territory of the anterior (superior) division of MCA. Persisting functional disability on discharge was also more severe in patients with the former than in patients with the latter. The neurological picture was polymorphous and it could sometimes even be misleading, as in some patients with a classical lacunar syndrome or with aphasia and unexpected sparing of speech areas. However, a few clinical syndromes apparently specific for involvement of a single MCA branch could be delineated, and in some instances they were highly predictive of embolism from heart or proximal artery.
Cerebrospinal fluid transthyretin in the neonate and blood–cerebrospinal fluid barrier permeability
Authors: Larsen Paul D. , Delallo Leonard
Published: January 2005

We measured transthyretin levels in the cerebrospinal fluid (CSF) of newborn infants, older children, patients with viral and bacterial meningitis, and adults with increased CSF protein levels. Neonatal CSF transthyretin levels are elevated disproportionately in comparison to levels in the other groups. We conclude that increased levels of transthyretin in the CSF of neonates are not explained by increased permeability of the blood–CSF barrier.
Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra
Authors: Rinne Juha O. , Mlic Jaana Rummukainen , Paljärvi Leo , Rinne Urpo K.
Published: January 2005

Regional neuronal loss in the substantia nigra was studied in relation to extrapyramidal symptoms and dementia in 12 patients with idiopathic Parkinson's disease(PD) and in 18 control subjects. Four areas of the right substantia nigra were investigated at the level of the superior colliculus and caudal red nucleus. In Parkinson's disease, the percentages of neurons, from the medial to the lateral part of the substantia nigra, were reduced to 49°, 31°, 41°, and 25° of the control values. The number of neurons in the lateral part showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor was less noticeable in patients with few neurons. The degree of dementia of the patients had a significant correlation only with neuronal loss in the medial part of the substantia nigra, suggesting, in view of the topographical organization of the neurons in the substantia nigra, that intact projections to the caudate nucleus and limbic and cortical areas are a prerequisite for normal cognitive functioning and that their dysfunction leads to clinical dementia.
Deprenyl suppresses the oxidant stress associated with increased dopamine turnover
Authors: Cohen Gerald , Spina Mary Beth
Published: January 2005

Tissue glutathione disulfide (GSSG) was studied as an index of changes in redox state in the striatum. When increased turnover of dopamine was provoked in mice by injection of haloperidol (1 mg/kg), the concentration of GSSG in the striatum tripled. Deprenyl (2.5 mg/kg) suppressed the rise in GSSG by 71.9%. These results indicate that deprenyl suppresses an oxidant stress associated with increased dopamine turnover.
Abnormal cough reflex in canine acrylamide neuropathy
Authors: Hersch Mark I. , McLeod James G. , Sullivan Colin E.
Published: January 2005

Coughing in response to irritation of the airways is a fundamental protective reflex that is dependent on rapidly adapting bronchopulmonary receptors and their vagal afferent fibers; reflex airway constriction, which is effected by vagomotor efferent fibers, usually accompanies coughing. Although dysfunction of vagally mediated cardiovascular and gastrointestinal reflexes is a well‐documented complication of autonomic neuropathy, to date there have been no studies of the effect of peripheral autonomic failure on the cough reflex. In the study reported here, we examined the effect of acrylamide‐induced neuropathy, a distal axonopathy, on the ventilatory and tracheomotor components of the cough reflex in conscious dogs. There was a reduction in the cough reflex in response to mechanical irritation of the large airways in the preclinical phase of the neuropathy, and the cough reflex was virtually abolished when the dogs had moderate neuropathy. Following withdrawal of the neurotoxin, there was a substantial recovery of the cough reflex in surviving animals. It is possible that the cough reflex may be reduced in patients with vagal neuropathy and that this might compromise protection of the airway.
Subdivisional involvement of nigrostriatal loop in idiopathic parkinson's disease and striatonigral degeneration
Authors: Goto Satoshi , Hirano Asao , Matsumoto Sadayuki
Published: January 2005

A topographical immunocytochemical analysis was performed on the substantia nigra from patients with idiopathic Parkinson's disease and striatonigral degeneration. Antibodies to tyrosine hydroxylase, a marker for nigrostriatal dopaminergic neurons, and to calcineurin, a marker for striatonigral projection fibers, were used in this study. There was a marked depletion of dopaminergic neurons in the substantia nigra of parkinsonian patients compared with control subjects, the reduction being greater in the lateral portion than in the medial portion (p < 0.001). Calcineurin immunoreactivity was densely distributed throughout the substantia nigra of patients with Parkinson's disease and control subjects. The numbers of dopaminergic neurons and of calcineurin‐immunoreactive fibers were markedly reduced in the lateral portion of the substantia nigra in all patients with striatonigral degeneration. Our results suggest that many symptoms of these two diseases may be due to disruption of the functions of the putamen and the lateral protein of the substantia nigra, which have dense reciprocal connections as part of the dopamine‐related nigrostriatal loop.
The hippocampus in experimental chronic epilepsy: A morphometric analysis
Authors: Bertram Edward H. , Lothman Eric W. , Lenn Nicholas J.
Published: January 2005

The effect of intermittent seizures on the pryramidal neurons of the hippocampus is largely unknown. To determine whether recurrent seizures centered in the hippocampus can produce neuronal loss in this region, a morphometric analysis was performed from standardized sections of hippocampus using 5 groups of animals: (1) surgical control subjects, (2) rats kindled by the rapidly recurring hippocampal seizure (RRHS) paradigm, (3) kindled rats with a few additional limbic seizures (528 ° 66 seizures), (4) kindled rats with may limbic seizures (1,523 ° 130 seizures), and (5) rats experiencing limbic status epilepticus (SE) induced by “continuous” hippocampal stimulation. The RRHS and SE protocols induced significant neuronal loss in the CA1 region, but no evidence was found for additional cell loss with increasing numbers of intermittent seizures. These intermittent seizures were, however, associated with a significant thickening of the basal and apical dendritic fields of the CA1 region. These finding indicate that intermittent seizures produce no significant hippocampal neuronal loss and may result in a hypertrophy of CA1 dendritic fields.
Interfer beta augments supperssor cell function in multiple sclerosis
Authors: Noronha Avertano , Toscas Angela , Jensen Mark A.
Published: January 2005

Suppressor cell function has been previously reported to be decreased in patients with progressive multiple sclerosis (MS). The abnormality could not be corrected in vitro and was present even after patients were treated with immunosuppressive agents. We now report that interferon beta augments suppressor function in vitro in progressive MS. Nonspecific suppressor cell function as measured in a concanavalin A (Con A) suppressor assay was reduced in 24 MS patients (mean percent suppression, 19.6 ± 2.2) when compared to 19 normal subjects (mean percent suppression, 35.0 ± 3.3). The data are highly significant (p < 0.001). When recombinant human interferon beta (103 units/ml) was added to lymphocyte cultures with Con A, Suppressor activity improved from 19.6 ± 2.2 to 37.8 ± 2.6 in MS (p < 0.001) and from 35.0 ± 3.3 to 46.2 ± 3.5 (p < 0.025) in control subjects. This study shows that recombinant interferon beta improves suppressor function in humans, an effect that is particularly significant in progressive MS.
Immunoregulatory properties of T‐cell lines derived from the systemic and intrathecal compartments: A phenotypic and functional study
Authors: Freedman Mark S. , Loertscher Rolf , Cashman Neil R. , Duquette Pierre , Blain Manon , Antel Jack P.
Published: January 2005

To determine whether immune regulation can differ within the intrathecal and systemic compartments, we compared phenotypic markers and functional properties of in vitro anti‐CD3 monoclonal antibody‐stimulated, interleukin 2‐expanded lymphoid cell lines simultaneously derived from peripheral blood and cerebrospinal fluid of individual donors (n = 9). We found that the proportions of total CD8+ T cells and of the putative CD8+ suppressor effector subset (CD28−) were lower in the cell lines derived from cerebrospinal fluid compared with cultures derived from peripheral blood (p p0.025 and p p0.005, respectively; paired t test), whereas the total CD4+ T‐cell proportion was higher (p p 0.025). For a donor subgroup with normal peripheral blood cell‐mediated activated suppressor function (63 ± 2), mean suppressor cell function mediated by unfractionated or CD8+ ‐enriched cells derived from cerebrospinal fluid was significantly lower (38 ± 7%; p 0.01, paired t test). For a donor subgroup with low peripheral blood cell‐mediated suppression (‐1 ± 10%), suppression mediated by cerebrospinal fluid cells was also low (9 ± 12%). Our results support the postulate that the immune response may be differentially regulated between the central nervous system and peripheral blood compartments.
Localization of epileptic foci using a large‐area magnetometer and functional brain anatomy
Authors: Tiihonen J. , Hari Dr R. , Kajola M. , Nousiainen U. , Vapalahti M.
Published: January 2005

We used a large‐area, 7‐channel, first‐order superconducting quantum interference device (SQUID) gradiometer to preoperatively determine the sites of epileptic foci in 2 patients with intractable temporal lobe seizures. The equivalent dipoles for the epileptic spikes were located with respect to external landmarks of the skull and in relation to the generation sites of magnetic auditory evoked responses. It was also possible, for the first time, to determine the location of the equivalent source using simultaneously measured data from seven locations only. The sites of the equivalent dipoles, in the right temporal lobe, agreed with the electrocorticographic and depth electrode recordings made during the operation.
A new point mutation within exon 5 of β‐hexosaminidase α gene in a Japanese infant with Tay‐Sachs disease
Authors: Nakano Takeshi , Nanba Eiji , Tanaka Akemi , Ohno Kousaku , Suzuki Yoshiyuki , Suzuki Kunihiko
Published: January 2005

A new point mutation within exon 5 of β‐hexosaminidase α subunit gene (guanine509→adenine; arginine170→glutamine) has been indentified as being responsible for the typical clinical and enzymological phenotype of infantile Tay‐Sachs disease in a Japanese infant. Expression of the mutant enzyme protein in the COS I cell system indicated that it is catalytically inactive and also is unstable. The patient is a compound heterozygote, and the exact abnormality in the other allele could not be identified except that it is not any of the other nine known mutations of the βhexosaminidase α. The data collectively suggest that the other allele is not producing stable messenger RNA (mRNA). The rapidly increasing number of mutations responsible for clinical and enzymological phenotypes and the very large number of statistically possible combinations among them for compound heterozygosity pose a serious pragmatic problem for classification and nomenclature of this group of rare genetic disorders.
Which risk factors predict the levodopa response in fluctuating Parkinson's disease?
Authors: Horstink M. W. I. M. , Zijlmans J. C. M. , Pasman J. W. , Berger H. J. C. , Korten J. J. , Van 't Hof M. A.
Published: January 2005

Three putative risk factors to the pathogenesis of end‐of‐dose–related fluctuations–severity of Parkinson's disease (PD), duration of PD, and duration of levodopa therapy–were evaluated in 39 patients with PD by measuring response duration and response magnitude to a single levodopa dose. After discontinuing levodopa therapy for 12 hours, the motor status of each patient was assessed before a single dose of 100 mg of levodopa plus 25 mg of decarboxylase inhibitor was given and at five 45‐minute intervals thereafter. Multiple regression analysis showed that the response duration was best predicted by the severity of PD. The response magnitude was significantly correlated both to the duration of PD and to the duration of levodopa therapy. It is argued, however, that the response magnitude was predicted by the duration of levodopa therapy. Our results are in accordance with those of other recent studies and indicate that variances in levodopa response duration and in levodopa response magnitude are caused by their own differential risk factor.
Tyrosine hydroxylase—immunoreactive neurons in the temporal lobe in complex partial seizures
Authors: Zhu Zhen‐qing , Armstrong Dawna L. , Grossman Robert G. , Hamilton Winifred J.
Published: January 2005

The anterior mesial portion of the temporal lobe removed from 16 patients who underwent surgery for the treatment of complex partial seizures was found to contain tyrosine hydroxylase–immunoreactive neurons. The distribution of these neurons was correlated with the underlying neuropathological features. Ammon's horn sclerosis was present in 8 patients; a ganglioglioma, in 7 patients; and an infarction in the distribution of the middle cerebral artery, in 1 patient. Tyrosine hydroxylase–immunoreactive neurons were found in Ammon's horn of 6 of the 8 patients with Ammon's horn sclerosis, and in the subiculum and entorhinal cortex of all 8 patients with the same pathology. None of these neurons were found in Ammon's horn of the 7 patients with a ganglioglioma, but were found in the subiculum of 5 of the 7 patients and in the entorhinal cortex of all 7 patients. Tyrosine hydroxylase immunoreactivity was also studied in 13 control autopsy specimens. No tyrosine hydroxylase–immunoreactive neurons were found in Ammon's horn or the subiculum of any of the control specimens, but were found in the entorhinal cortex of 6 of the 13 specimens. The tyrosine hydroxylase–immunoreactive neurons in the mesial portion of the temporal lobe of patients with complex partial seizures may contribute to the increased levels of tyrosine hydroxylase found in neurochemical studies of specimens taken at temporal lobectomy.
Selective sparing of NADPH‐diaphorase–somatostatin–neuropeptide Y neurons in ischemic gerbil striatum
Authors: Uemura Yoshihiko , Kowall Neil W. , Beal M. Flint
Published: January 2005

In the present study we investigated the relative vulnerability of neuronal subsets in the striatum to ischemia that was induced by bilateral transient ligation of the common carotid arteries in gerbils. After 4 days of survival, brains were evaluated using histochemical methods (NADPH‐diaphorase and silver degeneration procedures) and neurochemical methods with radioimmunoassays for somatostatin‐, neuropeptide Y–, and substance P–like immunoreactivity and measurements of amino acids using high‐pressure liquid chromatography with electrochemical detection. NADPH‐diaphorase–positive neurons were strikingly preserved in the ischemic dorsolateral portion of the striatum, in which there was severe neuronal loss. There was no significant depletion of NADPH‐diaphorase‐positive neurons in the striatum or cerebral cortex. Concentrations of neuropeptide Y–like and somatostatin‐like immunoreactivity were unchanged despite a significant 25% depletion of substance P–like immunoreactivity and gamma‐aminobutyric acid. Ischemic brain damage may be mediated by a neurotoxic effect of glutamate acting at the N‐methyl‐D‐aspartate (NMDA) receptor. Previous studies of NMDA excitotoxin lesions in rat striatum have shown a sparing of neurons containing NADPH‐diaphorase, somatostatin, and neuropeptide Y. The similar sparing of these neurons following ischemic lesions in gerbil striatum provides further evidence that NMDA receptor activation may play a role in ischemic injury.
Net production of cerebrospinal fluid is decreased by SCH‐23390
Authors: Boyson Sally J. , Alexander Alice
Published: January 2005

A high density of binding sites for the ligands 3H‐SCH‐23390 and 3H‐SKF‐83566 has been found in the choroid plexus. Although these sites have similar pharmacology to D1 dopamine receptors, the high‐affinity component of 3H‐SCH‐23390 binding in the choroid plexus has been identified as the 5‐HT1c subtype of serotonin receptor. We investigated the possible role of these receptors in modulating the production of cerebrospinal fluid (CSF) in rats. (R) SCH‐23390 produced up to a 50% decrease in net CSF production, compared to saline. This compound is partial agonist at 5‐HT1c serotonin receptors, and an antagonist at D1 dopamine receptors. The (S) enantiomer of SCH‐23390 (SCH‐23388) was ineffective. Drugs interacting with receptors for neurotransmitters in the choroid plexus may hold promise for the treatment of patients with increased intracranial pressure, including those with mass lesions, head trauma, acute or chronic hydrocephalus, or pseudotumor cerebri.
Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707M
Authors: Baker David L. , Reddy Usha Rani , Pleasure Samuel , Hardy Mattie , Williams Marge , Tartaglione Margaret , Biegel Jaclyn A. , Emanuel Beverly S. , Presti Patrizia Lo , Kreider Barbara , Trojanowski John Q. , Evans Audrey , Roy Amit R. , Venkatakrishnan Gita , Chen Jie , Ross Alonzo H. , Pleasure David
Published: January 2005

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33‐year‐old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low‐molecular‐weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence‐activated cell‐sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125–labeled mouse NGF with an affinity of 1.6 × 10−9 M, and short‐term treatment with NGF induces expression by the tumor cells of the proto‐oncogene, c‐fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor‐positive tumor cells. Thus, more than one‐third of such tumors might be responsive to the effects of NGF.