bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic changes in rabbit spinal cord after trauma: Magnetic resonance spectroscopy studies
Authors: Vink Robert , Noble Linda J. , Knoblach Susan M. , Bendall M. Robin , Faden Alan I.
Published: January 2005

Combined phosphorus and proton magnetic resonance spectroscopy (MRS), using double‐tuned surface coils, was used to monitor certain metabolic changes in the L‐3 spinal segment of anesthetized rabbits prior to and following experimental spinal cord trauma. Following severe trauma, resulting in spastic paraplegia, there was a delayed and progressive accumulation of lactic acid, a decline in intracellular pH, and a loss of high‐energy phosphates. Maximal alterations occurred between 2 and 3 hours after the trauma, with little further change by 4 hours. Histological examination 2 weeks after trauma showed tissue necrosis and cavitation. These findings support the concept of secondary tissue injury after spinal cord trauma and suggest that early changes in metabolism, as shown by MRS, may predict irreversible tissue damage.
Phenobarbital rheumatism in patients with brain tumor
Authors: Taylor Lynne P. , Posner Jerome B.
Published: January 2005

We reviewed the charts of 429 patients with primary brain tumors treated at Memorial Sloan‐Kettering Cancer Center to determine the frequency, clinical characteristics, and provocative factors involved in the development of the shoulder‐hand syndrome. Five percent (20/429) of patients developed this syndrome, which was strongly associated with phenobarbital use (p < 0.0001) and often produced more short‐term disability than the brain tumor itself.
Neuronal degeneration and neurofilament accumulation in the trigeminal ganglia in creutzfeldt‐jakob disease
Authors: Guiroy Don C. , Shankar Susarla K. , Gibbs Clarence J. , Messenheimer John A. , Das Sarala , Gajdusek D. Carleton
Published: January 2005

We report the pathological and immunohistochemical changes in the first‐order neurons in the trigeminal ganglia in Creutzfeldt‐Jakob disease (CJD). Degenerative changes consisted of cytoplasmic vacuolation and fenestration, abundant satellite cells, neurofilament accumulation in neurons, and axonal dystrophy with spheroid formation and torpedolike structures arising from the neuronal cytoplasm. Dystrophic axons, axonal spheroids, and some ganglion cells were labeled with monoclonal antibodies to a phosphorylated epitope of neurofilaments (200 kDa). Polyclonal antibodies to purified scrapie‐associated fibril/prion protein (molecular weight 27–30 kDa) extracted from scrapie‐infected hamster brains, as well as polyclonal and monoclonal antibodies to a synthetic 15–amino acid polypeptide of the 27‐ to 30‐kDa protein, demonstrated variable immunoreactivity with degenerating neurons in the CJD cases, but not in the controls. Furthermore, some of the satellite cells and dystrophic axons were stained by the antibodies to the synthetic peptide. These data indicate that the first‐order neurons of the trigeminal ganglia may form a route by which the CJD agent may travel from the brain to the periphery or vice versa. As in other chronic neurodegenerative diseases, disturbances of neuroaxonal transport seem to occur in CJD.
Absences in juvenile myoclonic epilepsy: A clinical and video‐electroencephalographic study
Authors: Panayiotopoulos Chrysostomos P. , Obeid Tahir , Waheed Ghazala
Published: January 2005

We report a prospective clinical and electroencephalographic study of 19 patients with juvenile myoclonic epilepsy and absence seizures. Absences began 1 to 9 (4.5 ± 2.5) years before myoclonic jerks and generalized tonic‐clonic seizures. Clinical manifestations during the absence ictus showed great variation, ranging from subtle or no overt features to severe impairment of consciousness, and severity was age related. Simple and complex absence seizures can occur in the same patient. The electroencephalographic features were distinct, with many interictal discharges, fragmentation of the paroxysms, and frequent polyspikes of varying numbers and amplitude for each spike‐slow wave component. The combined clinical‐electroencephalographic manifestations were characteristic and allow differentiation of absences in juvenile myoclonic epilepsy from typical absence seizures in other epileptic syndromes.
Lymphocyte subsets in the cerebrospinal fluid in active multiple sclerosis
Authors: Salonen Reijo , Llonen Jorma , Jägerroos Henrik , Syrjälä Hannu , Nurmi Tapio , Reunanen Mauri
Published: January 2005

We studied the relative number of lymphocyte subsets in the cerebrospinal fluid (CSF) of patients with active multiple sclerosis. The cells were double‐labeled with monoclonal antibodies and were studied using a fluorescence‐activated cell analyzer. The number of Leu2+ Leul5+ cells and Leu3+ Leul8+ cells was markedly reduced in the CSF but not in the peripheral blood of the patients. The number of Leu3+ Leu18+ cells was reduced also in the CSF of control patients (patients with other inflammatory or infectious neurological diseases).
Cytochrome C Oxidase—deficient myogenic cell lines in mitochondrial myopathy
Authors: Shimoizumi Hideo , Momoi Mariko Yoshida , Ohta Shigeo , Kagawam Yasuo , Momoi Takashi , Yanagisawa Masayoshi
Published: January 2005

In a patient with mitochondrial myopathy, the defect of cytochrome
ϵ oxidase activity was restricted to some muscle fibers. To isolate cell lines with or without oxidase activity from a single muscle sample, primary cultured cells were transformed by replication origin–defective simian virus 40, and then cloned. The clones were examined by cytochemical staining for cytochrome ϵ oxidase activity. Eight myogenic clones were completely devoid of activity, while the other myogenic and nonmyogenic clones were not. Deficiency of cytochrome ϵ oxidase was stable in culture for at least a year after serial passaging. The amount of mitochondrial DNA in cytochrome ϵ oxidase—deficient cells was the same as in control cells, and no deletion in the mitochondrial DNA was detected. Protein synthesis in mitochondria of the subunits of cytochrome ϵ oxidase and subunit 6 of the ATP synthase complex was markedly decreased, whereas synthesis of the other subunits encoded by mitochondrial DNA was normal. These cloned cell lines provide an excellent system for clarifying the cause of mitochondrial myopathy and for investigating nuclear‐mitochondrial genetic interaction.
Induction of aromatic‐l‐amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism
Authors: Boomsma F. , Meerwaldt J. D. , Veld A. J. Manin't , Hovestadt A. , Schalekamp M. A. D. H.
Published: January 2005

We evaluated the effect of administration of L‐dopa, alone or in combination with a peripheral decarboxylase inhibitor, on plasma levels of aromatic‐L‐amino acid decarboxylase (ALAAD). After single‐dose administration of L‐dopa plus benserazide (Madopar) in healthy subjects and in chronically treated patients with parkinsonism, plasma ALAAD followed for 2 to 3 hours fell, but returned to predosing levels within 90 minutes. Four groups of patients with idiopathic parkinsonism were studied during chronic treatment: Group I, no L‐dopa treatment (n = 31); Group II, L‐dopa alone (n = 15); Group III, L‐dopa plus benserazide (n = 28); and Group IV, L‐dopa plus carbidopa (Sinemet, n = 30). Plasma ALAAD 2 hours after dosing was normal in Groups I and II. ALAAD was increased threefold in Groups III and IV, suggesting induction of ALAAD by the coad‐ministration of a peripheral decarboxylase inhibitor. In a study of 3 patients in whom L‐dopa/benserazide was started, plasma ALAAD rose gradually over 3 to 4 weeks. Further detailed pharmacokinetic studies of L‐dopa, dopamine, and ALAAD in plasma and cerebrospinal fluid are required to determine if the apparent ALAAD induction by a peripheral decarboxylase inhibitor may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end‐of‐dose deterioration and on‐off phenomena.
Altered glucose metabolism in microvessels from patients with Alzheimer's disease
Authors: Marcus David L. , de Leon Mony J. , Goldman Jeffrey , Logan Jean , Christman David R. , Wolf Alfred P. , Fowler Joanna S. , Hunter Kevin , Tsai Jir , Pearson John , Freedman Michael L.
Published: January 2005

Microvessels isolated from temporal of cortex of patients with Alzheimer's disease showed decreased uptake of glucose when compared with vessels from age‐matched or young control subjects. This was due to decreased hexokinase activity in the Alzheimer samples, as determined by ion exchange chromatography. This finding was confirmed independently by determination of the phosphorylation constant for hexokinase, K3, using positron emission tomography. The results suggest that Alzheimer's disease may result from a global defect in brain energy metabolism.
Tomaculous neuropathy presenting as acute recurrent polyneuropathy
Authors: Joy Juan L. , Oh Shin J.
Published: January 2005

Tomaculous neuropathy (TN) is classically associated with the inherited, recurrent focal neuropathies. We report a case of TN manifesting as an acute recurrent polyneuropathy. A 28‐year‐old woman had 2 episodes of acute, ascending, symmetrical sensorimotor deficit. Teased nerve‐fiber preparation confirmed the presence of TN. Extensive investigations failed to reveal other cause for her symptoms. We believe that this case is unique and broadens the clinical spectrum of TN.
Increases in helper induced T cells and activated T cells in HTLV‐I–associated myelopathy
Authors: Itoyama Yasuto , Kira Jun‐ichi , Fujii Naoki , Goto Ikuo , Yamamoto Naoki
Published: January 2005

Using two‐color flow cytometric analysis, we studied peripheral blood lymphocyte subsets in 15 patients with human T‐cell lymphotropic virus type I–associated myelopathy. The percentage of CD 4+4B4+ cells (helper inducer T cell) was significantly increased in the patients with the myelopathy, compared with 16 healthy control subjects who were seronegative for human T‐cell lymphotropic virus type I. However, there was no difference in the percentage of CD4+2H4+ cells (suppressor inducer T cell) between the two groups. The ratio of CD4+4B4+ cells to CD4+ cells and CD4+4B4+ to CD4+ 2H4+ cells was also elevated in these patients. The percentage of CD4+DR+ cells and CD8+DR+ cells, both of which are phenotypically activated T cells, and the ratio of CD4+DR+ cells to CD4+ cells and of CD8+DR+ cells to CD8+ cells are also increased in the patients, compared with the control subjects. The percentage of Cd4+4B4+ cells showed positive correlations with values of spontaneous proliferation of peripheral blood lymphocytes and serum IgG level in patients with the myhelopathy.
Hyperkalemic periodic paralysis in Gordon's syndrome: A possible defect in atrial natriretic peptide function
Authors: Pasman J. W. , Gabreëls F. J. M. , Semmekrot B. , Renier W. O. , Monnens L. A. H.
Published: January 2005

We present the case of a 14‐year‐old boy who had secondary hyperkalemic periodic paralysis caused by Gordon's syndrome. This syndrome consists of hypertension, tubular acidosis, and hyperkalemia with normal glomerular filtration rate. The pathophysiological mechanism is still unknown. Pathophysiological studies suggest that in this disorder the kidney lacks sensitivity to atrial natriretic peptide. After treatment with hydrochlorothiazide, serum potassium and plasma aldosterone values, plasma rennin activity, and blood pressure became normal and the attacks of periodic paralysis disappeared.
Neurotrophic molecules
Authors: Snider W. D. , Johnson E. M.
Published: January 2005

Neurotrophic molecules have a profound influence on development events such as naturally occurring cell death, differentiation, and process outgrowth. Despite their Striking effects on developing neurons, a role for these molecules in the pathogenesis or therapy of neurological disease has not yet been defined. However, a variety of recent advances promise to provide the techniques necessary to asses the potential relevance of neurotrophic molecules to clinical neurology. In this article we review recent investigations into the biological effects, regulation of production, and mechanisms of action of the best characterized trophic molecule, nerve growth factor. In addition we review studies characterizing brain‐derived neurotrophic factor and other putative neurotrophic molecules. Finally, we discuss how pharmacological effects of these molecules may be relevant to the therapy of disease states as well as neural regeneration.
Abnormal systemic metabolism of iron, porphyrin, and calcium in fahr's syndrome
Authors: Beall Steven S. , Patten Bernard M. , Mallette Lawrence , Jankovic Joseph
Published: January 2005

Striopallidodentate calcinosis (Fahr's disease) is characterized clinically by seizures, rigidity, and dementia and pathologically by mineral deposition in the basal ganglia, dentate nucleus, and cerebral cortex. Disorders of iron and calcium‐phosphate metabolism are thought to play a role in its pathogenesis. We present the case of a patient with familial striopallidodentate calcinosis who had porphyria cutanea tarda, refractory anemia, and pseudohypoparathyroidism type 2. The serum level of ferritin was markedly increased, serum iron and iron‐binding capacity were below normal, and at autopsy she had deposition of iron in liver, spleen, bone marrow, and brain. She showed intermittent mild hypocalcemia, increased serum values of parathyroid hormone, elevated renal tubular reabsorption of phosphate, and low serum levels of 1,25‐dihydroxyvitamin D, suggesting blunted renal responsiveness to endogenous parathyroid hormone. Pseudohypoparathyroidism type 2 was confirmed by infusion of synthetic parathyroid hormone, which gave a normal urinary cyclic adenosine monophosphate response, but a blunted phosphaturic response. After splenectomy for hypersplenism and weekly phlebotomies, she showed progressive improvement in function, mental status, weight, and seizure control. The hypothesis advanced is that the underlying pathophysiology of the separate diseases contributed to the formation of the brain stones through mechanisms of defective iron transport and free radical production.
Intravenous phenytoin is an effective anticonvulsant in the kindling model
Authors: McNamara James O. , Rigsbee Lewis C. , Butler Linda S. , Shin Cheolsu
Published: January 2005

We reexamined the efficacy of the clinically effective anticonvulsant drug phenytoin in the kindling model. We investigated the effects of varying doses of intravenous phenytoin on serum concentrations and on several indexes of stimulation‐evoked kindled seizures. Intravenous phenytoin produced a dose‐dependent increase in serum phenytoin concentration and powerfully suppressed both limbic and clonic motor seizures. Although focal afterdischarge threshold was elevated to some extent, the most profound effect of phenytoin was limitation of seizure propagation. Variable and low serum concentrations of intraperitoneal or oral phenytoin may explain previous findings that phenytoin is only partly effective or ineffective against kindled seizures. Together with previous results with other drugs, the excellent correlation among drugs effective against human and kindled seizures strengthens the validity of this model. We suggest that the efficacy of experimental anticonvulsant drugs be established in the kindling model before initiation of clinical trials for partial and secondarily generalized seizures.
Intraventricular infusion of dopamine in Parkinson's disease
Authors: Horne M. K. , Butler E. G. , Gilligan B. S. , Wodak J. , Stark R. J. , Brazenor G. A.
Published: January 2005

A patient with serve end‐stage Parkinson's disease and troublesome fluctuations in motor function was treated with a long‐term intraventricular infusion of dopamine. There was modest improvement in speech and mentation and there was smoother control of motor symptoms that was superior to that achieved by conventional oral medications.
Creutzfeldt‐Jakob disease patients with congophilic kuru plaques have the missense variant prion protein common to Gerstmann‐Sträussler syndrome
Authors: Doh‐Ura Katsumi , Tateishi Jun , Kitamoto Tetsuyuki , Sasaki Hiroyuki , Sakaki Yoshiyuki
Published: January 2005

Congophilic kuru plaques, one of the pathological hallmarks in kuru and Gerstmann‐Sträussler syndrome, are sometimes present in patients with Creutzfeldt‐Jakob disease (CJD). The congophilic kuru plaques are composed partly of a host‐encoded prion protein, and a missense variant prion protein with the codon 102 proline‐to‐leucine change (Leu102) is commonly present in patients with Gerstmann‐Sträussler syndrome. To investigate the relationship between this syndrome and CJD with congophilic kuru plaques, we made a sequence analysis of the prion protein gene from patients with CJD, with or without congophilic kuru plaques. We found no alterations other than the Leu102 change, common to Gerstmann‐Sträussler syndrome, in one of the prion proteins alleles of the patient with congophilic kuru plaques. In the prion protein genotype analysis of other patients with CJD, the Leu102 allele was revealed to be carried heterozygously by 6 of 7 patients who had CJD with congophilic kuru plaques, yet no patient with CJD without congophilic kuru plaques had this allele. Interestingly, the Leu102 allele was also carried by some unaffected relatives of 3 patients with CJD with congophilic kuru plaques but with no apparent familial occurrence of a similar neurological disorder. Our findings show that CJD with congophilic kuru plaques should be categorized as belonging to Gerstmann‐Sträussler syndrome, not CJD, and also suggest that the variant prion protein with Leu102 is closely related to the amyloidgenesis seen in subjects with congophilic kuru plaques.
Hyperfractionated radiotherapy for children with brainstem gliomas: A pilot study using 7,200 cGy
Authors: Packer Roger J. , Allen Jeffrey C. , Goldwein Joel L. , Newall Joseph , Zimmerman Robert A. , Priest John , Tomita Tadanori , Mandelbaum David E. , Cohen Bruce H. , Finlay Jonathan L. , Sutton Leslie N. , D'Angio Giulio
Published: January 2005

Brainstem gliomas, constituting approximately 10% of all childhood central nervous system tumors, remain the most resistant of all brain tumors to therapy. A subgroup of high‐risk patients with tumors that diffusely involve the brainstem or that microscopically demonstrate foci of anaplasia on biopsy specimens rarely survive after treatment. Conventional doses of radiotherapy result in temporary clinical improvement in the majority of these high‐risk patients; however, few if any remain alive 18 months after treatment. Hyperfractionated radiotherapy, with delivery of larger numbers of smaller fractions of radiotherapy, is a possible way to increase tumor control without increasing neurological toxicity. In 1985, a multiinstitutional phase I/phase II trial, using 100 cGy of radiation therapy twice daily to a total dose of 7,200 cGy, was undertaken for patients with high‐risk brainstem gliomas. At the time of writing, 24 (69%) had developed progressive disease and 11 remained in continuous progression‐free remission. Actuarial progression‐free survival at 20 months is approximately 30% Twenty‐three of 31 evaluable patients had an objective radiographic response to therapy. In comparison to both historical control patients and patients treated in a previous trial using 6,480 cGy of hyperfractionated radiation therapy, there was a statistically significant improvement in progression‐free survival rate for patients treated with 7,200 cGy of hyperfractionated radiation therapy (p < 0.01). To date no patient has died as a result of treatment. Six patients developed transient neurological deterioration or cystic intralesional changes, as demonstrated on magnetic resonance imaging, within 6 weeks of the completion of radiotherapy. Postmortem examination performed in 7 patients did not disclose significant radiation necrosis. The results of this study suggest that further investigations into the potential benefits of hyperfractionated radiation therapy for children with brainstem gliomas are warranted.
Metabolic causes of myoglobinuria
Authors: Tonin Paola , Lewis Paulette , Servidei Serenella , Dimauro Salvatore
Published: January 2005

To evaluate the proportion of cases of myoglobinuria that can be ascribed to specific metabolic defects, we have studied eight enzymes–phosphorylase, phosphorylase kinase, phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), lactate dehydrogenase (LDH), carnitine palmitoyltransferase (CPT), and myoadenylate deaminase (MAD)–in muscle biospy specimens from 77 consecutive patients with myoglobinuria (documented in 44, suspected in 33). Enzyme defects were found in 36 patients: CPT deficiency in 17, phosphorylase deficiency in 10, phosphorylase kinase deficiency in 4, MAD deficiency in 3, PGK deficiency in 1, and a combined defect of CPT and MAD in 1. Exercise was the main precipitating factor, both in patients with and in those without detectable enzymopathies. Thirty patients had specific enzymopathies without myoglobinuria: 14 had phosphorylase deficiency, 9 had MAD deficiency, 3 had phosphorylase kinase deficiency, 3 had PFK deficiency, and 1 had PGAM deficiency. Systematic biochemical evaluation of muscle biopsy specimens revealed specific enzymopathies in about half of the patients with idiopathic myoglobinuria. The rest may have blocks of metabolic pathways not yet studied routinely, such as beta oxidation, or genetic defects of the sarcolemma, such as Becker's muscular dystrophy.
Degeneration of pyramidal projection neurons in Huntington's disease cortex
Authors: Cudkowicz Merit , Kowall Neil W.
Published: January 2005

We examined the distribution of neuropeptide Y immunoreactive local circuit neurons and nonphosphorylated neurofilament (SMI 32) immunoreactive pyramidal projection neurons in superior frontal cortex of patients with Huntington's disease and age‐matched control subjects to determine the histological counterpart of increased neuropeptide Y and decreased glutamate concentrations previously found in the cortex of patients with Huntington's disease. We found no difference between the relative density of neuropeptide Y neurons in Huntingon's disease and control brains in regions where the relative density of SMI 32 immunoreactive neurons was significantly reduced. Animal studies show that cortical local circuit neurons are resistant to N‐methyl‐D‐aspartate‐type excitotoxins such as quinolinic acid. Relative sparing of neuropeptide Y neurons in cerebral cortex with Huntington's disease may, therefore, be a result of excessive N‐methyl‐D‐asparate receptor activation.
Citrate‐Induced impairment of neuromuscular transmission in human and experimental autoimmune myasthenia gravis
Authors: Wirguin I. , Brenner T. , Shinar E. , Argov Z.
Published: January 2005

Two patients who underwent plamsapheresis for severe myasthenia gravis showed marked exacerbation of myasthenic weakness at the end of exchange sessions, in which citrate was used for anticoagulation. In one patient, improvement occurred after the administration of calcium but not after edrophonium. In rabbits and in rats with experimental autoimmune myasthenia gravis, decremental muscle response to 3 Hz repetitive nerve stimulation worsened significantly after injection of the citrate anticoagulant. The worsened neuromuscular transmission defect was reversed by the administration of calcium. When used for anticoagulation, citrate reduces serum ionized calcium levels and thus may aggravate myasthenic weakness and endanger patients during or immediately after plasmapheresis.
Skin biopsy findings in glycogenosis III: Clinical, biochemical, and electrophysiological correlations
Authors: Sancho Sara , Navarro Carmen , Fernández José M. , Domínguez Carmen , Ortega Arantxa , Roig Manuel , Cervera Carlos
Published: January 2005

Electron microscopy of skin specimens was performed in 4 patients (age range, 7 months–40 years) with glycogenosis III and revealed consistent abnormalities. Massive glycogen storage was observed in epithelial secretory cells of eccrine sweat glands and, less markedly, in smooth muscle fibers from the erector pili. Other cells, including Schwann cells of myelinated and unmyelinated fibers, were not affected. The extent of glycogen storage was similar in all patients and unrelated to age or duration of disease. The extralysosomal nature and selectivity of glycogen deposits, sparing fibroblasts and other cells, differ clearly from the findings in skin from patients with glycogenosis II. The purpose of this study was to show that glycogen deposits in glycogenosis III are not restricted to skeletal muscle and liver, and to assess the usefulness of skin biopsy in this disorder.
L‐Dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys
Authors: Hammerstad John P. , Woodward William R. , Gliessman Perry , Boucher Brain , Nutt John G.
Published: January 2005

The pharmacokinetics of levodopa (L‐dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2‐ to 3‐hour intravenous infusions of L‐dopa. Steady‐state L‐dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF: plasma ratio of 0.17. The disappearance of L‐dopa from plasma and cisternal CSF compartments fits an open, two‐compartment pharmacokinetic model. Although slower, the distribution and elimination half‐lives for L‐dopa from cisternal CSF (8.9 and 49.2 minutes, respectively) were of a similar magnitude to those from plasma (4.9 and 33.2 minutes, respectively). If cisternal CSF reflects brain extracellular fluid, then plasma pharmacokinetics of L‐dopa are a reasonable approximation of those in the brain. In contrast to cisternal CSF, the disappearance of L‐dopa from lumbar CSF fits an open, one‐compartment model with an elimination half‐life of 100 minutes. This indicates that the lumbar CSF compartment is unsuitable for investigation of the pharmacokinetics of L‐dopa in the brain.
Receptor alterations associated with spinal motoneuron degeneration in Bovine Akabane disease
Authors: Gundlach Andrew L. , Grabara Corrine S. G. , Johnston Graham A. R. , Harper Peter A. W.
Published: January 2005

Akabane disease in cattle is characterized by congenital abnormalities including arthrogryposis, which is characterized by a depletion of spinal ventral horn motoneurons, a loss of axons, and depletion of myelin in the lateral and ventral tracts. These neuropathological changes produced major reductions (70–80%) in the density of muscarinic cholinergic, glycine/strychnine, and central‐type benzodiazepine receptors in the ventral horn motor nuclei. The density of peripheral‐type benzodiazepine receptors and adenosine A1 receptors was dramatically increased (250–300%) in the lateral and ventral spinal columns, reflecting the proliferation of glial cells. Bovine Akabane disease represents a useful model for assessing the processes and consequences of neuronal degeneration and demyelination and has implications for human diseases such as amyotrophic lateral sclerosis.
Diagnosis of Maryland/German familial amyloidotic polyneuropathy using allele‐specific, enzymatically amplified, genomic DNA
Authors: Mendell Jerry R. , Jiang Xin‐Sheng , Warmolts John R. , Nichols William C. , Benson Merrill D.
Published: January 2005

Diagnoses of familial amyloidotic polyneuropathies have been traditionally based on attempts to distinguish clinical features and ancestry or geographic origin of cases. Most are associated with extracellular deposition of a variant prealbumin (also known as transthyretin). Recent molecular studies demonstrated eight distinct amyloid‐associated point mutations in the prealbumin gene on the long arm of chromosome 18 that are associated with hereditary amyloidosis. These findings provide for means of diagnosis using recombinant DNA methods. In a family with the Maryland/German type of familial amyloidotic polyneuropathy, the proband and 2 of 5 at‐risk offspring were diagnosed using the polymerase chain reaction. Allele‐specific enzymatic amplification of genomic DNA demonstrated the histidine‐58 variant prealbumin gene. This study confirms the point mutation of the prealbumin gene as a cause for this type of familial amyloidotic polyneuropathy. Preclinical diagnosis illustrates the potential for development of treatment strategies prior to disease onset.
Single skinned muscle fibers in duchenne muscular dystrophy generate normal force
Authors: Horowits Robert , Dalakas Marinos C. , Podolsky Richard J.
Published: January 2005

We measured the intrinsic mechanical properties and protein content of single skinned muscle fibers obtained from patients who had Duchenne muscular dystrophy. To check for possible nonspecific changes caused by muscle disease per se, we also studied the properties of muscle fibers obtained from patients exhibiting severe muscle weakness due to polymyositis. Relative to control fibers obtained from 4 patients with normal or nonmyopathic muscle, we found no significant change in the ability of muscle fibers from the patients with Duchenne muscular dystrophy or polymyositis to generate active tension in response to calcium or resting tension in response to stretch. In addition, we found no significant changes in the concentrations of the major contractile proteins myosin and actin, of the elastic protein titin, or of the structural proteins nebulin and α‐actinin. In contrast, immunocytochemical studies showed that dystrophin was absent in the biopsy specimens from the patients with Duchenne muscular dystrophy, but localized at the cell membrane in all of the other muscle biopsy specimens used in this study. These results indicate that myofibrils assemble and function normally in Duchenne muscular dystrophy. Therefore, the absence of dystrophin, which is the primary biochemical defect in this disease, leads to clinical weakness by causing the breakdown of muscle fibers that were once capable of generating normal force, while the surviving fibers exhibit normal contractility.
Cellular immunoregulatory mechanisms in the central nervous system: Characterization of noninflammatory and inflammatory cerebrospinal fluid lymphocytes
Authors: Matsui Makoto , Mori Kazuhiro J. , Saida Takahiko
Published: January 2005

Dual‐label flow cytometric analysis of cerebrospinal fluid (CSF) and blood lymphocytes with combinations of monoclonal antibodies such as CD4 plus CD45R or Leu8, and CD8 plus CD11b was performed in 37 patients with noninflammatory neurological disease (NINDs) to clarify the differences in cellular immunoregulatory mechanisms present in the central nervous system (CNS) and in the systemic circulation. In the CSF of patients with NINDs, the paucity of CD4+CD45R+ and CD8+CD11b+ cells was striking, whereas the same subsets accounted for substantial proportions in the blood. CD4+CD45R− and CD4+Leu8− cells as well as CD8+CD11b− cells increased in the CSF when compared with those in the blood. Seven patients with active multiple sclerosis (MS) and 10 patients with other inflammatory diseases in the CNS(CNS‐infl) were also studied. Patients with active MS were characterized by a consistent increase in percentage of CD4+CD45R− cells in the CSF, whereas an increase of CD4−CD45R+ cells in the CSF was a feature of the patients with CNS‐infl, when compared with patients with NINDs. These findings indicate that the CNS is routinely surveyed by particular subsets of lymphocytes different from those in the blood, and cellular immune reaction in the CNS varies according to the types of CNS inflammatory conditions.
Epileptic nystagmus
Authors: Furman Joseph M. R. , Crumrine Patricia K. , Reinmuth Oscar M.
Published: January 2005

We report a 52‐year‐old woman with episodes of vertigo accompanied by right beating nystagmus and left posterior temporoparietal sharp waves and spikes on electroencephalogram without change in level of consciousness. Electrooculography demonstrated that the episodes of nystagmus were not preceded by gaze deviation and that nystagmus slow component velocities were linear. This patient's epileptic nystagmus may have been the result of excitation of cerebral ocular pursuit pathways.
The accuracy of bedside neurological diagnoses
Authors: Chimowitz Marc I. , Logigian Eric L. , Caplan Louis R.
Published: January 2005

The accuracy of bedside diagnoses was propectively studied in 100 consecutive patients admitted to the neurology service at New England Medical Center, Boston. Each patients was evaluated independently by a junior resident, a senior resident, and a staff neurologist, who were required to make an anatomical and etiological diagnosis based solely on the history and physical examination. Fourteen patients were excluded because their diagnoses were known before admission. Of the remaining 86 patients, it was possible to confirm anatomical and etiological diagnoses in 40 by matching the clinical syndromes with highly specific laboratory findings. In other 46 patients, the diagnoses could not be confirmed because the laboratory studies (including magnetic resonance imaging) were negative or nondiagnostic. In the 40 patients with laboratory confirmed final diagnoses, the clinical diagnoses of the junior residents, senior residents, and staff neurologists were correct in 26 (65%), 30 (75%), and 31 (77%), respectively. There was a trend for error rates to be higher among junior residents than staff (p = 0.06). The errors by the junior residents,[senior residents], (staff) were attributed to incomplete history and examination in 4 [1] (0), inadequate fund of knowledge in 4 [3] (3), and poor diagnostic reasoning in 6 [6] (6). These results indicate that technology is not a panacea for our diagnostic difficulties and that there is room for improvement in our clinical skills, especially diagnostic reasoning.
Tissue distribution and transmission of mitochondrial DNA deletions in mitochondrial myopathies
Authors: Zeviani M. , Gallera C. , Pannacci M. , Uziel G. , Prelle A. , Servidei S. , DiDonato S.
Published: January 2005

By using a combination of Southern blot hybridization analysis, polymerase–chain reaction amplification, and direct nucleotide sequencing, we studied deletions of mitochondrial DNA (mtDNA) in several nonfamilial patients with progressive external ophthalmoplegia and Kearns‐Sayre syndrome, and in some of their direct relatives. Results suggest that the heteroplasmic mtDNA populations are already present at a very early stage of development, and that there is no direct transmission of mtDNA heteroplasmy by maternal inheritance.
Positron emission tomography in Shy‐Drager syndrome
Authors: Bhatt Mohit H. , Snow Barry J. , Martin W. R. Wayne , RN Sandra Cooper , Calne Donald B.
Published: January 2005

We studied the nigrostriatal dopaminergic pathway in 3 patients with Shy‐Drager syndrome, by using positron emission tomography and [18F]6‐fluoro‐1‐dopa to determine whether their parkinsonism correlated with impaired functional integrity of the presynaptic nigrostriatal pathway. One patient had short duration of disease, mild parkinsonism, and a normal positron emission tomographic scan, suggesting pathological changes functionally distal to the nigrostriatal pathway. Two patients with longer duration of disease had more severe parkinsonism and reduced [18F]6‐fluoro‐1‐dopa uptake, suggesting impaired nigrostriatal dopaminergic function with progression of Shy‐Drager syndrome.
Rhinocerebral mucormycosis: Management and survival after carotid occlusion
Authors: Galetta Steven L. , Wulc Allan E. , Goldberg Herbert I. , Nichols Charles W. , Glaser Joel S.
Published: January 2005

Rhinocerebral mucormycosis is a rare but often fatal fungal infection. We present 2 patients with mucormycosis complicated by internal carotid artery thrombosis. Magnetic resonance imaging was superior to computed tomography in localizing the pathological process. Subtotal resection of devitalized tissue and intravenous amphotericin B therapy resulted in a successful outcome for both patients. Prompt recognition of this disorder by using modern diagnostic and therapeutic modalities promises to improve survival rates.
Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging
Authors: Meguro Kenichi , Hatazawa Jun , Yamaguchi Tatsuo , Itoh Masatoshi , Matsuzawa Taiju , Ono Shuichi , Miyazawa Hidemitsu , Hishinuma Takashi , Yanai Kazuhiko , Sekita Yasuyoshi , Yamada Kenji
Published: January 2005

A combined magnetic resonance imaging and positron emission tomography study was performed on 21 patients with cerebrovascular risk factors but without neurological abnormalities. Our purpose was to investigate the hypothesis that periventricular hyperintensity (PVH) reflects ischemia. Periventricular hyperintensity was evaluated with a method we devised, and cerebral circulation and oxygen metabolism were evaluated with the oxygen‐15 steady‐state technique. We concluded that the brain with severe periventricular hyperintensity had abnormal circulation, although oxygen metabolism was not measurably affected. The role of a compensation mechanism under conditions of decreased oxygen supply was considered.
Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography
Authors: Gilman Sid , Adams Kenneth , Koeppe Robert A. , Berent Stanley , Kluin Karen J. , Modell Jack G. , Kroll Phillip , Brunberg James A.
Published: January 2005

Local cerebral metabolic rate for glucose was studied utilizing 18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET) in 14 chronically alcohol‐dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol‐dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol‐dependent patients with or without alcoholic cerebellar degeneration.
Selective reduction of quisqualate (AMPA) receptors in Alzheimer cerebellum
Authors: Dewar D. , Chalmers D. T. , Shand A. , Graham D. I. , McCulloch J.
Published: January 2005

Multiple sites involved in glutamatergic neurotransmission were examined in the cerebellar cortex of 6 patients with Alzheimer's disease and 6 age‐matched control patients by using quantitative ligand‐binding autoradiography. Quisqualate (AMPA) receptor binding was markedly reduced in the molecular layer of the cerebellum from patients with Alzheimer's disease (167 ± 13 pmoles/gm) compared with control patients (280 ± 13 pmoles/gm). In adjacent sections from the same patients and controls, there was preservation of kainate and N‐methyl‐D‐aspartate receptor binding in the cerebellum from patients with Alzheimer's disease compared with control patients. Neuropathological examination of the cerebellar cortex revealed the presence of plaques and preservation of Purkinje cells in the patients with Alzheimer's disease.
Genetic cause of a juvenile form of tay‐sachs disease in a lebanese child
Authors: Boustany Rose‐Mary N. , Tanaka Akemi , Nishimoto Junji , Suzuki Kunihiko
Published: January 2005

Abnormality in the β‐hexosaminidase α gene underlying the clinical phenotype of a Lebanese patient with a juvenile form of Tay‐Sachs disease has been studied. Clinical features were progressive spasticity, ataxia, and cognitive decline. The protein coding sequence of several β‐hexosaminidase α‐chain complementary DNAs isolated by polymerase chain reaction was completely normal except for a G‐to‐A transition at nucleotide position 1511 within exon 13, which resulted in substitution of the normal arginine 504 (CGC) with histidine (CAC). Although the patient was from a first‐cousin marriage, she was heterozygous for this mutation. The abnormality in the other allele, which is carried by the father, was not identified, except that it is neither of the two mutations responsible for the infantile Jewish Tay‐Sachs disease. Biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the α‐chain precursor, but the mature form of the α‐subunit was not detected.
HLA class II antigens and DNA restriction fragment length polymorphism in myasthenia gravis in japan
Authors: Morita Kazuyuki , Moriuchi Junko , Inoko Hidetoshi , Tsuji Kimiyoshi , Arimori Shigeru
Published: January 2005

Human leukocyte phenotypes and genes in the HLA class II regions were studied in 46 Japanese patients with myasthenia gravis. When the HLA phenotypes of the patients with myasthenia gravis were compared with the controls, an increased frequency of HLA‐DRw53 was observed in females less than 30 years of age. The genomic DNAs of the HLA‐DRw53‐positive patients and DRw53‐positive controls were analyzed by using four complementary DNA probes for HLA class II genes. With DQB complementary DNA as the probe, a higher incidence of the 6.5‐kb or 8.2‐kb BamHI fragment was observed in the patients (76.0%) compared with the controls (19.0%). In contrast, no significant difference was observed between patients and controls when complementary DNAs for DRB, DQA, and DPB were used as probes. These results indicate that the genetic background of Japanese females with early‐onset myasthenia gravis is different from other patients with myasthenia gravis, and that DQB genes can greatly influence the onset of myasthenia gravis.
Effects of head trauma from motor vehicle accidents on Parkinson's disease
Authors: Goetz Christopher G. , Stebbins Glenn T.
Published: January 2005

During 1 year we monitored changes in clinical disability scores in 10 patients with Parkinson's disease (PD) who sustained head trauma from motor vehicle accidents. Disability significantly increased immediately after trauma, but returned to baseline levels in subsequent weeks. These patients' signs deteriorated over the subsequent year, but this decline was equivalent to that of a matched control group with PD who did not have a motor vehicle accident or trauma. Based on these data, we conclude that trauma or stress caused by motor vehicle accidents can transiently exacerbate parkinsonian dysfunction without causing persistent increased disability or an alteration in disease course.
Intracerebral hemorrhage related to cerebral amyloid angiopathy and T‐PA treatment
Authors: Pendlebury William W. , Iole Elizabeth D. , Tracy Russell P. , Dill Ba Barbara A.
Published: January 2005

Tissue plasminogen activator (t‐PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t‐PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy a autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t‐PA. The cautious use of t‐PA with heparin in patients who are elderly or demented may be advisable.
Cerebrospinal fluid dynamics in the tardive cauda equina syndrome of ankylosing spondylitis
Authors: Confavreux Christian , Larbre Jean‐Paul , Lejeune Edouard , Sindou Marc , Aimard Gilbert
Published: January 2005

Typical cauda equina syndrome secondary to long‐standing ankylosing spondylitis is reported in a 63‐yerar‐old man. Radionuclide cisternography demonstrated a resorption defect of cerebrospinal fluid in the enlarged lumbosacral dural sac. After transient symptomatic improvement with acetazolamide, a lumboperitoneal shunt was placed. The rate of cerebrospinal fluid, isotope resorption became normal. In the 5 years of follow‐up, partial remission has been observed.
Cerebral hemodynamics in ischemic cerebrovascular disease
Authors: Powers William J.
Published: January 2005

During the past decade, technological advances have made it possible to measure regional cerebral hemodynamics in individual patients. Studies performed with these techniques have demonstrated that the degree of carotid stenosis correlates poorly with the hemodynamic status of the ipsilateral cerebral circulation. The primary determinant of cerebral perfusion pressure and blood flow under these circumstances is the adequacy of collateral circulatory pathways. Since collateral circulation varies from patient to patient, there is no critical degree of carotid stenosis that consistently produces hemodynamic compromise of the cerebral circulation. It is, thus, time to abandon the concept of the hemodynamically significant carotid stenosis as it relates to the pathogenesis and treatment of cerebrovascular disease. Measurement of regional cerebral hemodynamics have provided new insight into the pathogenesis of tranisent ischemic attacks and generated some preliminary data on the prognostic and therapeutic importance of chronic reductions in regional cerebral perfusion pressure. Further investigations into the importance of hemodynamic factors in ischemic stroke can now be based on accurate assessment of cerebral (not carotid or vertebrobasilar) hemodynamics in the context of other coexisting epidemiological, clinical, hematological, and angiographic risk factors.
Analysis of retroviral sequences in the spinal form of multiple sclerosis
Authors: Rozenberg Flore , Lefebvre Suize , Lubetzki Catherine , Lebon Pierre , Lyon‐Caen Olivier , Brahic Michel , Bureau Jean‐François
Published: January 2005

The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T‐cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen.