bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine D2 receptor density remains constant in treated Parkinson's disease
Authors: Guttman Mark , Seeman Philip , Reynolds Gavin P. , Riederer Peter , Jellinger Kurt , Tourtellotte Wallace W.
Published: January 2005

D2 dopamine receptor densities were measured in postmortem samples of the caudate nucleus and putamen from 36 parkinsonian patients. The relationship between the age of the patient, duration of the disease, and duration of L‐dopa therapy versus density of brain D2 dopamine receptors was examined using [3H]spiperone. Receptor density in parkinsonian tissues was constant over the age range of 56 to 90 years, as was the case for control tissues. Density did not change with duration of disease up to 24 years. Treatment with L‐dopa did not cause progressive reduction in receptor density. The diminished clinical response in the final stages of Parkinson's disease is not due to receptor dropout, and must depend on other factors.
Traumatic injury alters opiate receptor binding in rat spinal cord
Authors: Krumins Solveig A. , Faden Alan I.
Published: January 2005

Recent studies with dynorphin (an endogenous ligand for the κ‐opiate receptor) and receptor‐selective opiate antagonists have indicated a role for the κ‐receptor in the pathophysiology of spinal cord injury. However, no studies have specifically examined opiate receptor binding in relation to spinal injury. In the present experiments, opiate receptor binding was measured in spinal cord after traumatic injury in rats using the selective radioligands [3H][D‐Ala2, D‐Leu5]enkephalin (δ‐receptor agonist); [3H][D‐Ala2, MePhe4, Gly‐(ol)5]enkephalin (μ‐receptor agonist); and [3H]ethylketocyclazocine (κ‐receptor agonist). The specific binding of ethylketocyclazocine, but not the other agonists, showed a significant, time‐dependent, and localized increase at the injury site. Since dynorphin, which has been implicated as an injury factor after spinal trauma, shows similar localized increases after spinal injury, the present data are consistent with the hypothesis that up‐regulation of the κ‐receptor after injury may contribute to the subsequent secondary injury process.
Kinetics of microcirculatory, NAD/NADH, and electrocorticographic changes in cat brain cortex during ischemia and recirculation
Authors: Dora Eors , Tanaka Kartaro , Greenberg Joel H. , Gonatas Nicholas H. , Reivich Martin
Published: January 2005

Changes in microcirculation, the NAD/NADH redox state, and electrical activity during 2 hours of ischemia and 4 hours of reperfusion produced by middle cerebral artery occlusion and release were studied in cats. Twelve animals were classified into three groups of ischemia (mild, moderate, and severe) based on the severity of electrocorticographic (ECoG) depression at the end of the recovery period. Four animals were studied as controls. Occlusion of the middle cerebral artery (MCAO) resulted in a marked but similar degree of reduction in cerebral blood flow (CBF) in all three groups. After this initial change, CBF increased continuously during occlusion in the mild group. CBF in the moderate and severe groups remained at the same low level during the entire period of MCAO. Immediately after MCAO, NAD reduction was increased by approximately 50% in all groups. At the end of MCAO, while the NAD/NADH redox state returned to its pre‐ischemic reference level in the severe group, it remained markedly reduced in the mild and moderate groups. Removal of the clip led to slight reactive hyperemia in the mild and severe groups but not in the moderate group. Immediately after recirculation, NAD/NADH redox was shifted toward oxidation in all groups. However, this reoxidation of NADH was only partial in the mild and moderate groups, and a pronounced hyperoxidation occurred in the severe group. In spite of the similar behavior of CBF in the recovery period, a marked secondary NAD reduction occurred in the moderate group during the recirculation period. It is suggested that this represents cessation of mitochondrial electron transport in the dying cells, accompanied by stimulated anaerobic glycolysis in other cells. The spontaneous oxidation of NADH during MCAO and its hyperoxidation during recirculation in the severe group may be due to an insufficient supply of reducing equivalents into the mitochondria and/or the release of oxidizing substances in the brain.
Diagnostic value of cerebrospinal fluid anti–myelin basic protein in patients with multiple sclerosis
Authors: Warren Kenneth G. , Catz Ingrid
Published: January 2005

Prevalence and titer of total, free, and bound cerebrospinal fluid anti–myelin basic protein (MBP) antibodies as well as free/bound ratios were determined in four groups of patients with multiple sclerosis (MS) and three groups of controls. All patients with clinically active MS have elevated levels of total anti‐MBP, which may be present in either free or bound form. Patients whose disease is in remission have undetectable anti‐MBP levels, and some patients with clinically stable disease with residual disability may have detectable antibody titers. Chronically progressive MS is usually associated with high levels of antibody in the bound rather than the free form, resulting in a low or normal free/bound ratio. In contrast, MS exacerbations are characterized by relatively high levels of free anti‐MBP in the cerebrospinal fluid, resulting in a high free/bound antibody ratio. Bound anti‐MBP was also detected in elevated levels in 1 patient with subacute sclerosing panencephalitis and 2 of 8 patients with postinfectious encephalomyelitis. Although elevated levels of cerebrospinal fluid anti‐MBP are not specific for MS, they are strongly associated with disease activity and may be involved in the pathogenesis of demyelination in patients with MS.
Membrane defects in duchenne dystrophy: Protease affecting sarcoplasmic reticulum
Authors: Nagy Béla , Samaha Frederick J.
Published: January 2005

Human muscle sarcoplasmic reticulum (SR) yields three major protein bands. The percent distribution of the mean values of the bands from 15 normal human muscles was 55.4, 14.6, and 30.0 for the 100, 55, and 45‐kDa mass proteins, respectively. A mean distribution similar to that in normal muscle SR was found in preparations from 7 patients with polymyositis and from 7 patients with myotonic dystrophy. In 12 preparations from patients with Duchenne dystrophy, the protein distribution differed from that of preparations from normal muscle. The 100‐kDa mass protein band was decreased, whereas the 55‐ and 45‐kDa mass bands were increased. Protease inhibitors pepstatin A, antipain, and leupeptin, as well as ethyleneglycol‐bis(aminoethyl ether)‐N,N,N′,N′‐tetraacetic acid or ethylenediaminetetraacetic acid, significantly reduced this change. However, some of the changes cannot be prevented by the addition of inhibitors and must be expressed in vivo. Neither protease inhibitors nor chelators affected SR preparations from normal muscle. We found a five‐ to ten‐fold increase in calcium‐activated neutral protease activity in Duchenne dystrophic muscles that degraded the calcium‐adenosinetriphosphatase of SR. The active protease was identified as the cytoplasmic calpain II. The increased activity in Duchenne muscles may explain many reported abnormalities.
Free kappa light chains in multiple sclerosis spinal fluid
Authors: Rudick Richard A. , Pallant Adam , Bidlack Jean M. , Herndon Robert M.
Published: January 2005

Based on prior reports of free light chains of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), we quantitated free kappa and lambda chains and whole IgG concentrations using sensitive and specific radioimmunoassays (RIAs). The RIA for free kappa chains had a sensitivity of 0.25 μg/ml and was capable of specifically measuring free kappa chains in whole CSF or serum even in the presence of a 4‐log excess of whole IgG. By RIA, free kappa chains were detected in CSF samples from 33 (84%) of 39 MS patients but in only 1 (2.4%) of 42 controls. The control patients included 10 with noninfectious inflamatory diseases and 9 with central nervous system infections. The concentration of free kappa chains in the CSF of the MS patients was 1.40 ± 1.21 μg/ml. Free kappa chains were concentrated in the CSF 71‐ to 120‐fold relative to reference proteins. In contrast, increased levels of free lambda chains or of whole IgG were nonspecific; abnormalities were seen in controls with infections or inflammatory diseases as often as in MS patients. These studies suggest that the measurement of free kappa light chains may have important diagnostic usefulness, since the specificity of the finding for MS appears to be high.
Chronic inflammatory demyelinating polyneuropathy of infancy: A corticosteroid‐responsive disorder
Authors: Sladky John T. , Brown Mark J. , Berman Peter H.
Published: January 2005

We present the clinical, electrophysiological, and histopathological findings in 6 children with early‐onset chronic inflammatory demyelinating neuropathy. The clinical features initially suggested a genetically determined disorder in each patient. Sural nerve biopsy showed changes of chronic demyelination with multifocal endoneurial edema and mononuclear cellular infiltrates. All children improved with corticosteroid therapy.
Reduced phospholipase D activity in brain tissue samples from Alzheimer's disease patients
Authors: Kanfer Julian N. , Hattori Hiroshi , Orihel Danka
Published: January 2005

Biochemical examinations of brain tissue samples obtained from patients with Alzheimer's disease have revealed a decreased quantity of the neurotransmitter acetylcholine and reduced activity of choline acetyl‐transferase (ChAT), the enzyme responsible for acetylcholine formation. It has been suggested that the choline moiety of lecithin, a substitute ubiquitously present in membranes of mammalian cells, could be mobilized for acetylcholine formation. The activity of phospholipase D, an enzyme which releases choline directly from lecithin, was measured in homogenates of Alzheimer brain tissue and found to be reduced by 63%. ChAT activity was reduced by 58% and 5′‐nucleotidase activity was reduced by 27% in these homogenates.
PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline
Authors: Young Anne B. , Penney John B. , Starosta‐Rubinstein Simon , Markel Dorene S. , Berent Stanley , Giordani Bruno , Ehrenkaufer Richard , Jewett Douglas , Hichwa Richard
Published: January 2005

Fifteen drug‐free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18F‐2‐fluoro‐2‐deoxyglucose (18F‐FDG) uptake. All patients had abnormal indices of caudate metabolism on PET scanning, whereas in patients with early disease indices of putamen metabolism and CT measures of caudate atrophy were normal. Indices of caudate metabolism correlated highly with the patients' overall functional capacity (r = 0.906; p < 0.001) and bradykinesia/rigidity (r = −0.692; p < 0.01). Indices of putamen metabolism correlated highly with motor functions: Chorea (r = −0.841; p < 0.01), oculomotor abnormalities (r = −0.849; p < 0.01), and fine motor coordination (r = −0.866; p < 0.01). Indices of thalamic metabolism correlated positively with dystonia (r = 0.559; p < 0.05). The data suggest that PET scanning with 18F‐FDG is a sensitive measure of brain dysfunction in Huntington's disease and that basal ganglia metabolism is highly correlated with the overall functional capacity of individual patients and with the degree of their motor abnormalities.
Saccade responses to dopamine in human MPTP‐induced parkinsonism
Authors: Hotson J. R. , Langston E. B. , Langston J. W.
Published: January 2005

Depletion of dopamine content in the substantia nigra resulting from 1‐methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine (MPTP) toxicity produces parkinsonism. Management of 3 patients with MPTP‐induced parkinsonism required drug holidays during which there was a state of dopamine depletion followed by dopamine replacement. We used this opportunity to study the effect of the selective loss of pars compacta dopaminergic cells on vertical and horizontal saccade (fast) eye movements. During the drug holidays, visually guided saccades were hypometric and had long latencies but retained a normal saccade velocity–amplitude relationship. Dopamine agonists or precursors improved the accuracy and reaction times of saccades in all directions, but not their velocity. Two of the three patients also had intermittent blepharospasm during dopamine depletion. During the episodes of blepharospasm, saccade responses became slow eye movements. MPTP causes a dopaminergic‐responsive disorder of saccade initiation that is similar to idiopathic parkinsonism. The inhibition of voluntary eyelid opening during MPTP‐induced blepharospasm further increases this impairment of fast eye movements and altered saccade velocity, presumably via the pars reticulata of the substantia nigra.
Cholinergic muscarinic binding by human lymphocytes: Changes with aging, antagonist treatment, and senile dementia of the Alzheimer type
Authors: Rabey Jose M. , Shenkman Louis , Gilad Gad M.
Published: January 2005

In peripheral blood lymphocytes (mixed lymphocytes isolated on a Ficoll‐Hypaque density gradient) derived from normal human subject, cholinergic muscarinic binding capacity was found to increase with age. In contrast, lymphocytes derived from patients with “probable” senile dementia of the Alzheimer type (SDAT) exhibited a marked reduction in binding capacity. Treatment of these patients with antimuscarinic drugs was associated with increased muscarinic binding by lymphocytes. These results indicate that cholinergic muscarinic binding by peripheral blood lymphocytes may be useful in the study of alterations associated with aging and SDAT, as well as in evaluating changes induced by certain cholinergic drug treatments.
Spastic pure motor monoparesis
Authors: Ashizawa Tetsuo , Rolak Loren A. , Hines Marc
Published: January 2005

Pure motor hemiplegia (PMH) is, in most cases, caused by a lacunar infarction. However, pure motor monoparesis (PMM), i.e., isolated motor involvement with spasticity in one limb, has drawn little attention. We studied prospectively 5 patients with PMM and found that it was always due to a mass lesion in the contralateral superficial cerebral hemisphere. Our observation suggests that PMM should not be regarded as simply a variant of PMH.
Botulism in a patient with jejunoileal bypass
Authors: Freedman M. , Armstrong R. M. , Killian J. M. , Boland D.
Published: January 2005

A 45‐year‐old woman was diagnosed as having the unclassified form of botulism. Her intestines may have been predisposed to colonization with Clostridium botulinum because of a jejunoileal bypass procedure that had been done several years earlier. One other similar case has been reported.
Acute herpetic and postherpetic neuralgia: Clinical review and current management
Authors: Portenoy Russell K. , Duma Christopher , Foley Kathleen M.
Published: January 2005

The pain of acute herpes zoster (HZ) may be severe, but it is usually transitory. A minority of patients, with the elderly at particular risk, go on to develop persistent, severe, often disabling pain called postherpetic neuralgia. Though the clinical features of these conditions are well known, the pathology of PHN is poorly described and the pathogenesis of the pain in both remains conjectural. During the past 60 years, an extraordinary number of pharmacological, anesthetic, and surgical therapies have been applied in an attempt to ameliorate the symptoms of acute herpes zoster, enhance its healing, prevent its transition to postherpetic neuralgia, and treat the pain of those with this complication. Relatively few treatments have been studied in a controlled manner, and fully reliable, safe, and effective therapeutic approaches for preventing and treating postherpetic neuralgia have not yet been found. This review summarizes current information on the epidemiology, clinical features, and pathology of herpes zoster and postherpetic neuralgia, and critically examines the accumulated experience with the various treatments. Guidelines for management are suggested.
Vasopressin in Alzheimer's disease: A study of postmortem brain concentrations
Authors: Mazurek Michael F. , Bed M. Flint , Bird Edward D. , Martin Joseph B.
Published: January 2005

Vasopressin (AVP) and its analogues are reported to improve learning‐ and memory‐related performance in experimental animals, and perhaps also in humans. Memory impairment is a clinical hallmark of the dementing disorder, Alzheimer's disease. We have examined AVP concentrations in postmortem brain tissue from 12 patients with histologically confirmed Alzheimer's disease and 13 control subjects. AVP was measured by a highly specific and sensitive radioimmunoassay, validated by parallel inhibition curves and high‐performance liquid chromatography. Alzheimer brains had either normal or slightly increased AVP levels in the neocortex, which does not have AVP cell bodies. Significant reductions in AVP content were found in the hippocampus, nucleus accumbens, and globus pallidus interna Levels were normal in all other regions studied. Abnormalities of the brain vasopressin system may contribute to the memory deficit associated with Alzheimer's disease.
Hemispheric brain damage in unilateral status epilepticus
Authors: Soffer Dov , Melamed Eldad , Assaf Yaakov , Cotev Shamay
Published: January 2005

A 20‐year‐old woman with psychomotor seizures developed prolonged unilateral status epilepticus followed by coma, right hemiparesis, fever, liver failure, and eventually death. Neuropathological findings included severe neuronal ischemic cell change and massive brain edema, essentially restricted to the left cerebral hemisphere. Massive destruction of the hemisphere involved in epileptic activity with sparing of the contralateral hemisphere provides supportive evidence that in humans prolonged seizure activity can cause permanent brain damage.
Magnetic resonance imaging of the midbrain in Parkinson's disease
Authors: Duguid J. R. , De La Paz Robert , DeGroot Jack
Published: January 2005

We have analyzed magnetic resonance images of the midbrain in patients with Parkinson's disease, and have found that there is a narrowing of the signal from the pars compacta of the substantia nigra relative to controls. The nature of the histological changes that may be responsible for this effect is discussed. Magnetic resonance imaging has the potential of becoming a useful diagnostic tool in the management of parkinsonism.
Wernicke's encephalopathy in patients on peritoneal dialysis or hemodialysis
Authors: Jagadha Venkita , Deck John H. N. , Halliday William C. , Smyth H. S.
Published: January 2005

Although the occurrence of Wernicke's encephalopathy (WE) in patients on dialysis is frequently alluded to, review of the literature reveals only 3 described cases. We describe 5 patients on dialysis who developed WE in the absence of alcoholism or other predisposing factors. The clinical diagnoses included uremic encephalopathy (2 patients), dysequilibrium syndrome (1), dialysis dementia (1), and brainstem hemorrhage (1). At postmortem examination, classic findings of WE were evident. The rarity of WE in patients on dialysis may in part be explained by studies indicating a genetic defect in transketolase activity. Patients on dialysis are also potentially at risk for thiamine deficiency because of anorexia, vomiting, and intravenous alimentation. Other factors altering thiamine requirements, such as glucose load or infections, may also contribute. Preventable and potentially curable, WE should be suspected in all patients on dialysis who have an unexplained neurological picture.
Beyond receptors: Multiple second‐messenger systems in brain
Authors: Worley Paul F. , Baraban Jay M. , Snyder Solomon H.
Published: January 2005

Second‐messenger systems play a major role in mediating neurotransmitter actions. In recent years our understanding of the organization and function of two prominent second‐messenger systems has progressed rapidly—the adenylate cyclase and phosphoinositide systems. Guanosine triphosphate–binding proteins, which are especially abundant in brain, couple transmitter receptors to the key second‐messenger generating enzymes in both of these systems. Whereas activation of adenylate cyclase produces a single intracellular messenger, cyclic AMP, stimulation of the phosphoinositide system generates at least two, inositol trisphosphate and diacylglycerol. Inositol trisphosphate mobilizes calcium from intracellular stores, and diacylglycerol, like cyclic adenosine monophosphate, activates a phosphorylating enzyme, protein kinase C. These second‐messenger systems are particularly enriched in the brain where they modulate many aspects of synaptic transmission.
Reinnervation of the hippocampal perforant pathway zone in Alzheimer's disease
Authors: Hyman B. T. , Kromer L. J. , van Hoesen G. W.
Published: January 2005

The perforant pathway originates from the entorhinal cortex of the anterior parahippocampal gyrus and terminates on the outer dendritic branches of the granule cells of the dentate gyrus and pyramidal cells of the subiculum and hippocampus. It carries the principal cortical input to the hippocampal formation. Destruction of the perforant pathway in experimental animals leads to a partial deafferentation of its target neurons, followed by a robust sprouting of acetylcholinesterase (AChE) terminals in the deafferented perforant pathway zone. In Alzheimer's disease, the cells of origin of the perforant pathway are laden with neurofibrillary tangles. AChE staining in the terminal zone of the perforant pathway in Alzheimer's disease shows several distinct patterns that are not found in control brains. These changes are consistent with the results of experimental studies demonstrating reinnervation in laboratory mammals, including nonhuman primates. The results suggest that in Alzheimer's disease sprouting of AChE‐containing systems occurs in the hippocampal formation in response to disease‐related cellular damage in the entorhinal cortex.
Class II antigen expression and inflammatory cells in the guillain‐barré syndrome
Authors: Pollard J. D. , Baverstock Julia , McLeod J. G.
Published: January 2005

Monoclonal antibodies to T‐lymphocyte subsets and Class II molecules (Ia) have been used to characterize the inflammatory infiltrate in nerve tissue biopsied from 2 patients in the acute phase of Guillain‐Barré syndrome; the findings were compared with those in control nerve specimens. Normal control nerve was treated in the same way. In normal nerves, Class II molecules are expressed on endothelial cells and on occasional mononuclear and perineurial cells. In Guillain‐Barré nerves the inflammatory infiltrate consisted mainly of Class II–positive cells of the monocyte– macrophage lineage and of lesser numbers of T4 and T8 lymphoid cells. T4 cells predominated in perivascular collections. In the more severely affected patient, there was a marked increase of Class II molecules expressed on endothelial cells, perineurial cells, and most Schwann cells. Schwann cells associated with unmyelinated fibers and the Schwann cell processes of denervated Büngner bands all expressed Class II molecules. These histological changes were less marked in the more mildly affected patient. It is suggested that the expression of Class II molecules on the myelin forming cell, the Schwann cell, has important implications for the pathogenesis of the demyelination that occurs in Guillain‐Barré syndrome.
Hemophilus influenzae meningitis in the rat: Behavioral, electrophysiological, and biochemical consequences
Authors: Konkol Richard J. , Chapman Louisa , Breese George R. , Collier Albert M. , Kilts Clinton , Finley Charles , Vogel Richard R. , Mailman Richard B. , Bendeich Elizabeth G.
Published: January 2005

Hemophilus influenzae is the most common cause of bacterial meningitis in children, and a high percentage of survivors are at risk for long‐term sequelae. To explore the mechanisms responsible for these sequelae, a neonatal rat model was used to define the behavioral, electrophysiological, and biochemical changes following meningitis. Three days after inoculation of 6‐day‐old rats with a minimum of 1 × 107 colony‐forming units of a virulent Hemophilus influenzae, type b, cerebrospinal fluid and blood were cultured to confirm the presence of meningitis and bacteremia, respectively. At this time, forebrain norepinephrine and dopamine levels were significantly elevated in meningitic rats when standardized on a wet‐weight basis. No changes in brain serotonin or heart norepinephrine levels could be found in the 9‐day‐old rats. No residual changes were found in steady‐state concentrations of norepinephrine or dopamine in surviving adult rats. However, survivors that had had meningitis as neonates showed significant impairment in active and passive avoidance learning tasks and demonstrated a significantly higher level of activity during a habituation period in circular photocell activity cages. No change in the flinch‐jump threshold was detected. Brainstem auditory evoked potentials showed delays of various waves in 3 of 10 Hemophilus influenzae type b–treated adult rats tested. These rats also exhibited markedly augmented locomotory responses to d‐amphetamine (1 mg/kg), suggesting a long‐lasting perturbation of central monoamine neuronal transmission.
Abduction nystagmus in internuclear ophthalmoplegia
Authors: Zee David S. , Hain Timothy C. , Carl James R.
Published: January 2005

We tested the hypothesis that abnormalities of the abducting eye in internuclear ophthalmoplegia reflect an adaptive process that helps overcome the adduction weakness of the opposite eye. This response operates under the constraints of Hering's law of equal innervation: any attempt to increase the innervation to a weak muscle in one eye must be accompanied by a commensurate increase in innervation to the yoke muscle in the other eye. In 4 patients with internuclear ophthalmoplegia, we patched one eye for 1 to 5 days to allow time for the central nervous system to optimize innervation for the habitually viewing eye. We predicted that there would be a conjugate adjustment of innvervation that would diminish the abduction overshoot and backward postsaccardic drift made by the habitually viewing eye. This was the case in 3 of our 4 patients. Our findings show that the abduction nystagmus is a manifestation of a normal adaptive response in some patients with INO.
Disorders of the autonomic nervous system: Part 1. Pathophysiology and clinical features
Authors: McLeod J. G. , Tuck R. R.
Published: January 2005

Autonomic dysfunction may result from diseases that affect primarily either the central nervous system or the peripheral autonomic nervous system. The most common pathogenesis of disturbed autonomic function in central nervous system diseases is degeneration of the intermediolateral cell columns (progressive autonomic failure) or disease or damage to descending pathways that synapse on the intermediolateral column cells (spinal cord lesions, cerebrovascular disease, brainstem tumors, multiple sclerosis). The peripheral autonomic nervous system may be damaged in isolation in the acute and subacute autonomic neuropathies or in association with a generalized peripheral neuropathy. The peripheral neuropathies most likely to cause severe autonomic disturbance are those in which small myelinated and unmyelinated fibers are damaged in the baroreflex afferents, the vagal efferents to the heart, and the sympathetic efferent pathways to the mesenteric vascular bed. Acute demyelination of the sympathetic and parasympathetic nerves in the Guillain‐Barré syndrome may also cause acute autonomic dysfunction. Although autonomic disturbances may occur in other types of peripheral neuropathy, they are rarely clinically important.
Recovery of vision after ischemic lesions: Positron emission tomography
Authors: Bosley Thomas M. , Dann Robert , Silver Frank L. , Alavi Abass , Kushner Michael , Chawluk John B. , Savino Peter J. , Sergott Robert C. , Schatz Norman J. , Reivich Martin
Published: January 2005

We used [18F]fluoro‐2‐deoxyglucose positron emission tomography (PET) to study serial changes in the local cerebral metabolic rate of glucose in 5 patients with ischemic lesions of the posterior afferent visual system causing homonymous visual field defects. All 5 patients had striking impairment of glucose metabolism in the striate cortex shortly after ictus. In 2 patients, visual field defects abated, and repeat PET scans showed reduced size of the metabolic lesion and improvement of striate metabolism. Three patients did not recover vision, and repeat PET scans did not show improvement. Patients who recovered vision had ischemic lesions outside the occipital lobe, while those who did not experience improvement had primary damage to the occipital lobe itself.
Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease
Authors: Sims Neil R. , Finegan Janet M. , Blass John P.
Published: January 2005

Alzheimer's disease is associated with selective neuronal loss, the cause of which is undetermined. Evidence indicating a predisposing genetic factor associated with this disease suggests that important alterations may be expressed in tissues other than the brain. Because abnormal glucose and energy‐related metabolism have been identified in both in vivo and in vitro studies of brain, we conducted a study to examine related measures in cultured skin fibroblasts from six patients with Alzheimer's disease and seven age‐matched controls. After 60 minutes' incubation, the production of 14CO2 from [U‐14C]glucose and lactate production were significantly higher in the cells from the group of patients with Alzheimer's disease. The increase of 14CO2 production, but not the production of lactate, was most evident after a more rapid period of metabolic activity in the first 10 minutes of incubation. By contrast, 14CO2 production from [U‐14C]glutamine, which is probably the major substrate of oxidative metabolism in these cells, was significantly reduced in the Alzheimer's disease cells following longer (120‐minute) incubations. Oxygen uptake by cell suspensions was also significantly reduced in the group with Alzheimer's disease. These results indicate that complex metabolic differences are expressed in nonneural tissues from some patients with Alzheimer's disease and may provide important clues to the pathogenesis of this disorder.
Inactivation of GM1‐ganglioside β‐galactosidase by a specific inhibitor: A model for ganglioside storage disease
Authors: Singer Harvey S. , Tiemeyer Michael , Slesinger Paul A. , Sinnott Michael L.
Published: January 2005

This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM1‐ganglioside β‐galactosidase (β‐D‐galactopyranosylmethyl‐p‐nitrophenyltriazene [β‐GalMNT]) and neuroblastoma X glioma hybrid cells (NG108–15), we suppressed β‐galactosidase activity for up to 72 hours. Coincidental with suppression of this enzyme to levels less than 1% of control, we found up to a nine‐fold accumulation of its substrate, the GM1‐ganglioside, and the ultrastructural appearance of membranous cytoplasmic bodies. β‐GalMNT treatment suppressed growth but had little effect on the specific activity of choline acetyltransferase, lactate dehydrogenase, or other lysosomal enzymes including galactosylceramidase. This model should permit studies of the neurophysiological effects of increased ganglioside accumulation and their reversibility.
Immunoblotting of Creutzfeldt‐Jakob disease prion proteins: Host species—specific epitopes
Authors: Bockman Jeffrey M. , Prusiner Stanley B. , Tateishi Jun , Kingsbury David T.
Published: January 2005

Creutzfeldt‐Jakob disease (CJD) is a rare dementia that is generally found in older people and is caused by unusual infectious pathogens or prions. Using rabbit antisera raised against hamster scrapie prion proteins (HaPrPSc), we identified by immunoblotting human CJD prion proteins (HuPrPCJD) in the brains of 14 patients dying of CJD. Extracts from 6 of the patients were transmitted to mice after prolonged incubation. The rabbit antisera raised against HaPrPSc also reacted with the mouse CJD prion proteins (MoPrPCJD) found in the brains of these experimentally infected mice. When mice were immunized with HuPrPCJD, they produced antibodies that reacted with HuPrPCJD but not with MoPrPCJD. Mice immunized with MoPrPCJD produced antibodies to neither murine nor human prion proteins. Our results provide evidence for host species‐‐specific epitopes on prion proteins. The existence of such epitopes is consistent with the apparent lack of an immune response during prion infections and the finding that prion protein molecules are encoded by host genes.
Site of penetrating brain lesions causing chronic acquired stuttering
Authors: Ludlow Christy L. , Rosenberg Jeanette , Salazar Andrés , Grafman Jordan , Smutok Mike
Published: January 2005

Ten subjects exhibited acquired stuttering that had persisted for 10 to 15 years following penetrating missile wounds sustained during the Vietnam War. None had a history of developmental or chronic adult stuttering. In comparison with other head‐injured subjects and normal control subjects, the subjects with acquired stuttering had significant deficits in skilled rapid hand movements and oral and speech movements, suggesting a motor control disorder. The identified brain lesions of the acquired stuttering group were on the right in 5 subjects, on the left in 4, and bilateral in 1. The internal and external capsules, the frontal white matter, and the striatum were more frequently involved in the acquired stuttering group than in other head‐injured subjects (p ≤ 0.05). This speech rhythm and rate disorder was not associated with evident cortical lesions in either hemisphere but with predominantly unilateral lesions of the subcortical pyramidal and extrapyramidal systems.
Fixation‐off—sensitive epilepsy in eyelid myoclonia with absence seizures
Authors: Panayiotopoulos Chrysostomos P.
Published: January 2005

Fixation‐off—sensitive epilepsy is documented in a patient with eyelid myoclonia with absences. A series of simple electroencephalographic techniques showed that elimination of visual fixation is the actual stimulus for the eyelid myoclonus.
In vivo labeling of blood T cells: Rapid traffic into cerebrospinal fluid in multiple sclerosis
Authors: Hafler David A. , Weiner Howard L.
Published: January 2005

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). In MS patients being treated with anti–T11, a murine monoclonal antibody which recognizes the sheep red blood cell receptor, it was found that peripheral blood T cells were labeled in vivo by the antibody. Furthermore, anti‐T11 did not lyse cells or enter the cerebrospinal fluid (CSF). In CSF specimens obtained by serial lumbar punctures from patients with progressive MS who received five daily infusions of anti‐T11, 70 ± 12% of the T cells had mouse antibody bound to their surface by 72 to 96 hours. No in vivo staining of CSF T cells was observed in patients infused with anti‐T4, a murine monoclonal antibody that was not found to label T cells in vivo. These results demonstrate that there is rapid movement of lymphocytes from the peripheral blood to the CNS in patients with progressive MS. This rapid trafficking of T cells suggests that the ongoing pathological process within the CNS may be closely linked to the peripheral immune system and may have implications for the monitoring and treatment of MS.
Mitochondrial hydroxyapatite deposits in spinocerebellar degeneration
Authors: Munoz D. G. , Emery E. S. , Highland R. A.
Published: January 2005

We report the presence of crystalline deposits of calcium hydroxyapatite in the mitochondria of 2 children with sporadic spinocerebellar degeneration. The deposits, identified by electron microscopy, were found in the mitochondria of neurons and smooth muscle cells in one patient and in only smooth muscle cells in the second child, but not in other cell types. The calcific nature of the deposits was confirmed by laser microprobe mass analysis. The calcium overload may interfere with mitochondrial function, as has been shown in the cardiomyopathic strain of the Syrian hamster, a model of the cardiomyopathy of Friedreich's ataxia.
Detection of varicella‐zoster virus nucleic acid in neurons of normal human thoracic ganglia
Authors: Gilden Donald H. , Rozenman Yaacov , Murray Ronald , Devlin Mary , Vafai Abbas
Published: January 2005

Tissue sections from four normal human thoracic ganglia were hybridized in situ with a varicella‐zoster virus—RNA probe. Varicella‐zoster virus was detected in two of four ganglia, localized exclusively in neurons. The detection of latent varicella‐zoster virus genetic material in thoracic ganglia provides further evidence of varicella‐zoster virus latency at multiple levels of the human neuraxis and supports the notion that the neuron is the primary site of herpesvirus latency.
Central motor conduction in motor neuron disease
Authors: Hugon J. , Lubeau M. , Tabaraud F. , Chazot F. , Vallat J. M. , Dumas M.
Published: January 2005

Central motor conduction was assessed in 13 patients with motor neuron disease and in 15 control subjects. All patients with motor neuron disease, even those without clinical pyramidal signs, had slowed central motor conduction, and in some the delays were asymmetrical. Evoked motor potentials represent a new and reliable method to detect physiological abnormalities of central motor pathways early in the course of motor neuron disease.
Mamillary body atrophy in Wernicke's encephalopathy: Antemortem identification using magnetic resonance imaging
Authors: Charness Michael E. , DeLaPaz Robert L.
Published: January 2005

We used magnetic resonance imaging to determine the volume of the mamillary bodies in 9 patients with chronic Wernicke's encephalopathy, 7 patients with presumed Alzheimer's disease, and 37 control patients. The mean mamillary body volume (± standard error) was 21.3 ± 5.8 mm3 in Wernicke patients, 40.1 ± 3.7 mm3 in Alzheimer patients, and 51.7 ± 2.5 mm3 in control patients. Seven of nine (78%) patients with chronic Wernicke's encephalopathy had smaller mamillary bodies than 36 of 37 control patients and 7 of 7 Alzheimer patients. The decrease in mamillary body volume was related neither to patient age nor to degree of ventricular enlargement, and most likely reflects the mamillary body atrophy that is grossly apparent at autopsy in up to 81% of Wernicke patients. This technique provides a means of identifying the most specific macroscopic lesion of chronic Wernicke's encephalopathy.
Functional anatomy of pentylenetetrazol and electroshock seizures in the rat brainstem
Authors: Miller John W. , McKeon Ann C. , Ferrendelli James A.
Published: January 2005

The ability of discrete brainstem injection of γ‐vinyl‐γ‐aminobutyric acid (GVG), an irreversible inhibitor of γ aminobutyric acid transaminase, to prevent pentylenetetrazol (PTZ) seizures and maximal electroshock seizures (MES) was studied and compared in rats. PTZ seizures were prevented by GVG injections in the anterior thalamus, the caudal hypothalamus, the superior colliculus, cerebellar nuclei, and in a large area of the medial medullary, pontine, and mesencephalic tegmentum encompassing the vestibular nuclei, the reticular formation, and portions of the central gray. GVG injections in the substantia nigra did not protect against PTZ seizures. In contrast, tonic hindlimb extension in MES was prevented consistently by injections in the substantia nigra. A minority of injections in the vestibular nuclei, cerebellar nuclei, and parts of the reticular formation also protected against tonic hindlimb extension of MES. These results indicate a striking difference in the functional anatomy of PTZ‐induced seizures and MES. PTZ seizures appear to be mediated by an extensive system involving the reticular formation, diencephalic regions in the vicinity of the anterior medial thalamus and caudal hypothalamus, and bulbar regions which give rise to descending motor pathways to the spinal cord. In contrast to PTZ seizures, MES appears to be mediated by a different neuroanatomical substrate with the present data implicating only the substantia nigra definitely in that process.
Alzheimer's disease and other dementing illnesses in a defined united states population: Incidence rates and clinical features
Authors: Schoenberg Bruce S. , Kokmen Emre , Okazaki Haruo
Published: January 2005

In this study, for the first time to our knowledge, all new cases of Alzheimer's disease and other dementing illnesses have been documented in a well‐defined United States community. A total of 178 patients in an average annual at‐risk population of 18,991 persons over age 29 developed dementia during 1960 through 1964 in Rochester, Minnesota, yielding an average annual incidence rate of 187.5 new cases/100,000/year. The corresponding rate for clinically and/or pathologically diagnosed Alzheimer's disease (the most common cause of dementia in this community) was 123.3 new cases/100,000/year, based on 117 cases. The incidence rates for both dementia in general and Alzheimer's disease in particular rise dramatically with age. All patients were followed to death or to 1982, and the median survival was 63 months. These data include only those in the community who came to medical attention, but they yield higher rates than studies in Scandinavia, indicating a relatively high level of case ascertainment.
Neurological syndrome following bilateral damage to the head of the caudate nuclei
Authors: Richfield Eric K. , Twyman Roy , Berent Stanley
Published: January 2005

We describe a persistent behavioral disorder associated with bilateral destruction of the head of the caudate nuclei. The findings in this case support a role for the caudate nuclei in behavioral functions and are interpreted in view of recent anatomical and physiological information on the connections of the caudate nuclei with the prefrontal cortex.
Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: An update
Authors: Packer Roger J. , Sutton Leslie N. , Bilaniuk Larissa T. , Radcliffe Jerilynn , Rosenstock Jeffrey G. , Siegel Kathy R. , Bunin Greta R. , Savino Peter J. , Bruce Derek A. , Schut Luis
Published: January 2005

Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long‐term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twentyfour patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3–10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2–6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long‐term outcome. Full‐scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84–133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long‐term outcome.
Selective brainstem injury in an asphyxiated newborn
Authors: Roland Elke H. , Hill Alan , Norman Margaret G. , Flodmark Olof , MacNab Andrew J.
Published: January 2005

We report the clinical, radiological, and neuropathological features of selective brainstem injury in an asphyxiated term infant. Disproportionate injury to thalamus, basal ganglia, and brainstem with relative sparing of cortex and subcortical white matter is observed occasionally after acute total asphyxia. Although this entity has been well documented neuropathologically, the specific computed tomographic findings have not been reported previously to our knowledge, and the clinical correlation is recognized rarely.
Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients
Authors: Crisostomo Edgardo A. , Duncan Pamela W. , Propst Martha , Dawson Deborah V. , Davis James N.
Published: January 2005

We conducted a double‐blind pilot study of 8 patients with established cerebral infarction to evaluate the effect of a single dose of amphetamine on recovery of motor function using the Fugl‐Meyer scale. Four patients received amphetamine; the rest were given placebo. All underwent a session of physical therapy. Patients treated with amphetamine obtained greater increments in motor scores than the controls. Along with animal studies, these findings may allow the development of a pharmacological approach to stroke rehabilitation.
Acquired ocular motor apraxia due to bilateral frontopariental infarcts
Authors: Pierrot‐Deseilligny Charles , Gautier Jean‐Claude , Loron Philippe
Published: January 2005

A case of acquired ocular motor apraxia in a 78‐year‐old man is reported. Disordered saccades and pursuit movements in the horizontal and vertical planes were recorded electro‐oculographically. Magnetic resonance imaging showed bilateral border‐zone infarcts, involving the frontal lobes and the superior part of the inferior pariental lobules.
Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography
Authors: Gilman Sid , Markel Dorene S. , Koeppe Robert A. , Junck Larry , Kluin Karen J. , Gebarski Stephen S. , Hichwa Richard D.
Published: January 2005

We studied local cerebral metabolic rates for glucose (lCMRglc) with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET) in 30 patients with olivopontocerebellar atrophy (OPCA) and 30 age‐matched control subjects without neurological disease. The diagnosis of OPCA was based on the history and physical findings and on the exclusion of other causes of cerebellar ataxia by means of laboratory investigations. Computed tomographic scans revealed some degree of atrophy of the cerebellum in most patients with OPCA, and many also had atrophy of the brainstem. PET studies in these patients revealed significant hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem in comparison with the normal control subjects. A significant relationship was found between the degree of atrophy and the level of lCMRglc in the cerebellum and brainstem. Nevertheless, several patients had minimal atrophy and substantially reduced lCMRglc, suggesting that atrophy does not fully account for the finding of hypometabolism, lCMRglc was within normal limits for the thalamus and cerebral cortex. The data suggest that PET/lCMRglc may be useful as a diagnostic test in patients with the adult onset of cerebellar ataxia.