bluuebunny/crossref_metadata_2025 huggingface dataset:
Mu‐opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy
Authors: Frost J. James , Mayberg Helen S. , Fisher Robert S. , Douglass Kenneth H. , Dannals Robert F. , Links Jonathan M. , Wilson Alan A. , Ravert Hayden T. , Rosenbaum Arthur E. , Snyder Solomon H. , Wagner Henry N.
Published: January 2005

Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C‐carfentanil to measure mu‐opiate receptors and 18F‐fluoro‐deoxy‐D‐glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C‐carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C‐carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.
Measurement of immunoreactive myelin basic protein peptide (45–89) in cerebrospinal fluid
Authors: Gupta Manjula K. , Whitaker John N. , Johnson Claire , Goren Hershel
Published: January 2005

To measure myelin basic protein (MBP)‐like material in cerebrospinal fluid, we compared two radioimmunoassays, both using the same antiserum to MBP but one using peptide (45‐89) as the radioligand and standard (peptide assay), and the other using purified MBP as the radioligand and standard (MBP assay), with respect to their diagnostic sensitivity. Cerebrospinal fluid specimens from 185 patients with definite multiple sclerosis (MS) (n = 27), possible MS (n = 63), probable MS (n = 24), and other neurological disease (n = 71) were analyzed using both assays. The diagnostic sensitivity of the peptide assay was significantly better than that of the MBP assay in those with definite MS (sensitivity 59% and 30%, respectively); there was no significant difference in specificity. The peptide assay also showed better correlation with disease activity than the MBP assay: 14 patients classified as having active MS showed significantly higher sensitivity (78.6% versus 38%, p < 0.04) when compared to patients with inactive disease. The MBP assay showed no significant difference between these two groups. Besides the increase in sensitivity, the actual molar concentrations of immunoreactive MBP detected using this peptide assay were considerably higher than those found using the MBP assay. These results show that the use of MBP antisera capable of recognizing epitopes present in the carboxyl half of MBP peptide (45–89) results in more sensitive detection of immunoreactive MBP when used with MBP peptide (45–89) as radiolabeled ligand in the assay.
Uveomeningoencephalitis in a human immunodeficiency virus type 2—seropositive patient
Authors: Hormigo Adília , Bravo‐Marques J. M. , Souza‐Ramalho P. , Pimentel J. , Teixeira Carmo , Martins Rui
Published: January 2005

A 35‐year‐old woman developed longstanding uveitis and later a uveomeningoencephalitis of unknown origin and died of toxoplasmal brain abscesses. The presence of immunological impairment, human immunodeficiency virus type 2 (HIV‐2) seropositivity, and multinucleated cells in the brain led us to suspect neurotropic properties for HIV‐2 similar to those of HIV‐1.
Fatal adenovirus meningoencephalitis in a bone marrow transplant patient
Authors: Davis Daron , Henslee P. Jean , Markesbery William R.
Published: January 2005

We describe a bone marrow transplant patient with fatal subacute adenovirus meningoencephalitis, the first such patient reported. Neuropathological examination revealed unique, bilaterally symmetrical degeneration in the inferomedial temporal cortex, amygdaloid nuclei, hippocampi, hypothalamus, and some brainstem nuclei. Viral intranuclear inclusions were noted in these areas by light microscopy and confirmed by electron microscopy. Identification was authenticated by viral culture and the isolation of adenovirus from cerebral cortical tissues, and further confirmed by immunofluorescence and serological methods.
Plasmapheresis alleviates neuropathy accompanying IgM anti—Myelin‐Associated glycoprotein paraproteinemia
Authors: Haas David C. , Tatum Arthur H.
Published: January 2005

A patient with peripheral neuropathy accompanying a benign IgM anti—myelin‐associated glycoprotein paraproteinemia has been treated successfully by plasmapheresis for over a year, and during this time, fluctuations in the patient's symptoms and signs have correlated with variations in the serum IgM level. These results suggest that plasmapheresis may be more beneficial for such neuropathies than indicated previously, and they add to the evidence implicating the paraprotein as the cause of the neuropathy.
Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase
Authors: Hartung Hans‐Peter , Schäfer Bärbel , Heininger Kurt , Toyka Klaus V.
Published: January 2005

Macrophages have been implicated in myelin damage in experimental autoimmune neuritis (EAN). We examined a possible pathogenetic role of toxic oxygen species elaborated by macrophages in EAN by administering oxygen radical scavengers. Early treatment of rats with either catalase or superoxide dismutase (10,000 U/kg/day) protected animals from the development of EAN. Treatment delayed until there was clinical manifestation of EAN (day 13) still markedly attenuated the severity of the disease, as evidenced by clinical assessment, electrophysiological studies, and morphological observation. In cell culture, macrophages from sham‐treated controls generated heightened oxidative metabolic responses indicating in vivo macrophage activation. Addition of catalase or superoxide dismutase abrogated or diminished chemiluminescence and production of reactive oxygen intermediates by macrophages ex vivo. Our findings underscore the importance of macrophages in EAN and provide evidence that, in this model, macrophagederived reactive oxygen intermediates contribute to damage of the myelin sheath.
Nervous system involvement in Fabry's disease: Clinicopathological and biochemical correlation
Authors: Kaye Edward M. , Kolodny Edwin H. , Logigian Eric L. , Ullman M. David
Published: January 2005

A detailed neuropathological and biochemical study was performed to evaluate the accmulation of ceramide trihexoside within the central and peripheral nervous systems of 2 patients with Fabry's disease. Luxol fast blue–staining lipid was noted in the leptomeninges and in the choroidal stroma; biochemical studies showed increased quantities of ceramide trihexoside in the cerebrospinal fluid. The permeable blood‐brain barrier and blood‐nerve barrier regions of the central and peripheral nervous systems contained increased quantities of ceramide trihexoside. Some central nervous system nuclei associated with autonnomic function were also noted to store lipid. Other areas of increased ceramide trihexoside accumulation included specific cortical and brainstem structures. Possible sources for this selective accumulation of ceramide trihexoside within the central and peripheral nervous systems include transport of glycolipid from the systemic vascular network and retrograde transsynaptic glycolipid transport.
Complications of long‐term anticoagulation
Authors: Petty G. W. , Lennihan L. , Mohr J. P. , Hauser W. A. , Weitz J. , Owen J. , Towey C.
Published: January 2005

We used life‐table techniques to determine risks of morbidity and mortality associated with long‐term warfarin treatment in an anticoagulation clinic. Cumulative risks for life‐threatening complications and warfarin‐related death among all patients were 1% at 6 months, 5% at 1 year, and 7% at 2 and 3 years. Cox regression analysis using age as a continuous variable failed to show an effect of age on cumulative risks of complication. The occurrence of a minor complication during the course of therapy did not place patients at higher risk for developing a major complication that would prompt discontinuation of therapy or cause death. There was no statistically significant difference between the cumulative risks of patients anticoagulated for cerebrovascular disease and the cumulative risks of patients anticoagulated for other indications.
Effects of anterior temporal lobectomy on language function: A controlled study
Authors: Hermann Bruce P. , Wyler Allen R.
Published: January 2005

This study represents the first prospective controlled investigation of preoperative versus postoperative (6 months) language function in patients who underwent partial resection of the dominant (n = 15) or nondominant (n =14) anterior temporal lobe for treatment of medically refractory epilepsy. Language dominance was confirmed by in tracarotid sodium amytal test. Thirteen of the 15 patients undergoing anterior temporal lobectomy of the dominant hemisphere were operated on under local anesthesia in order to map language and memory functions intraoperatively. Using a standardized language/aphasia battery, we found a significant trend of worse preoperative language function in patients with dominant hemisphere temporal lobe foci in comparison to patients with nondominant foci. Following anterior temporal lobectomy, neither group showed any significant losses in language function, whereas the dominant hemisphere temporal lobe group showed significant improvement in receptive language comprehension and associative verbal fluency.
Cerebral blood flow requirement for brain viability in newborn infants is lower than in adults
Authors: Altman Denis I. , Powers William J. , Perlman Jeffrey M. , Herscovitch Peter , Volpe Sara L. , Volpe Joseptemberh J.
Published: January 2005

Measurements of regional cerebral blood flow (CBF) with positron emission tomography in adult humans with cerebrovascular disease have demonstrated consistently that values below 10 ml/(100 gm · min) occur only in infarcted brain. Although experimental data suggest that the newborn brain may be more resistant to ischemic injury than the adult brain, the minimum CBF necessary to sustain neuronal viability in newborn infants is unknown. We have measured CBF with positron emission tomography in 16 preterm and 14 term newborn infants and have determined the relationship between CBF and subsequent brain function as assessed by neurological examination and developmental assessment. The range of mean CBF in the preterm infants was 4.9 to 23 ml/(100 gm · min) and the range of mean CBF in the term infants was 9.0 to 73 ml/(100 gm · min). Five preterm infants and one term infant with mean CBF less than 10 ml/(100 gm · min) survived. Three of these 5 preterm infants, with mean CBF of 4.9, 5.2, and 9.3 ml/ (100 gm · min, respectively, have normal neurological examinations and Bayley Scales of 80 or greater at 6, 6, and 24 months of age, respectively. One (mean CBF 6.9) has normal cognitive development (Bayley 103) and a mild spastic diplegia at age 19 months, and one infant (mean CBF 6.2) has a left hemiparesis and a Binet IQ score of 70 at age 33 months. The term infant, with a mean CBF of 9.0 ml/(100 gm · min), was developing normally when he died of Septembersis at age 5 months. These data indicate that mean CBF as low as 5 ml/(100 gm · min) in newborn infants can be associated with normal subsequent neurological development and therefore with preservation of a substantial number of cortical/ neurons. Since the minimal CBF below this value necessary to maintain neuronal viability in newborn infants remains to be determined, measurements of CBF in the newborn period should not be used in determination of brain death.
An isoelectric focusing study in herpes simplex virus encephalitis
Authors: Grimaldi Luigi M. E. , Roos Raymond P. , Manservigi Roberto , Spear Patricia G. , Lakeman Fred D. , Whitley Richard J.
Published: January 2005

To establish an early reliable diagnostic test for herpes simplex virus (HSV) type 1 encephalitis (HSVE), we used isoelectric focusing (IEF) and an IEF‐overlay technique with radiolabeled HSV glycoprotein B (gB) to study 7 serum and 12 cerebrospinal fluid (CSF) samples from 12 patients with presumed or biopsy‐proved HSVE. Blood‐brain barrier damage and increased intra‐blood‐brain barrier IgG synthesis were detected in 5 of the 7 patients with HSVE. CSF oligoclonal bands were found in 6 of 11 patients. Using an IEF‐overlay technique, we detected anti‐gB antibody in all serum (7 of 7) and in 10 of 12 CSF samples. Anti‐gB antibody was found in 4 of 6 CSF specimens obtained within the first week of disease (days 3 to 5) and in all samples collected later in the disease. The pH range of anti‐gB antibody activity was broad (4.5 to 9.5), indicating a heterogeneous immune response to HSV. A hematogenous origin of the CSF antibody was suggested because anti‐gB antibody appeared in serum before matched CSF and because both serum and matched CSF had a similar antibody IEF pattern. Local production of anti‐gB antibody was suggested in some cases because of a greater prominence of anti‐gB antibody in CSF than in matched sera and because CSF oligoclonal bands had anti‐gB antibody activity. In contrast, only one of 6 CSF samples from patients with multiple sclerosis had gB antibody activity; in this case, anti‐gB antibody activity did not correspond in isoelectric point location to oligoclonal bands. The IEF‐HSV‐gB overlay technique may be a useful diagnostic test for HSVE and a valuable research tool for studying qualitative aspects of the HSV humoral immune response.
The neuropathology of aminergic nuclei in Alzheimer's disease
Authors: Zweig Richard M. , Ross Christopher A. , Hedreen John C. , Steele Cynthia , Cardillo Joseptemberh E. , Whitehouse Peter J. , Folstein Marchshal F. , Price Donald L.
Published: January 2005

Neuronal loss and the presence of neurofibrillary tangles (NFTs) within aminergic nuclei were examined in a series of patients with Alzheimer's disease (AD). Neuromelanin‐containing neurons within the locus ceruleus and large nucleolus‐containing neurons within the dorsal raphe nucleus and the central superior (raphe) nucleus were counted in 25 patients with AD and in 12 age‐matched control subjects. Numbers of NFTs were quantified in the same regions. Counts were compared with clinical data, including psychiatric evaluations, available for 21 of the patients with AD. Within the locus ceruleus in the patients with AD, abnormalities were more severe at mid level than at caudal or rostral levels (p < 0.01). Within the dorsal raphe nucleus, neuronal loss was most severe caudally (p < 0.05). NFTs, but not neuronal loss, were demonstrated within the central superior nucleus. Neuronal and NFT counts did not correlate at individual levels; the relative severity of both pathological processes was consistent from level to level within nuclei but was less consistent between nuclei. Neuronal loss correlated inversely with age, particularly within the locus ceruleus. Duration of disease correlated inversely with counts of NFTs, particularly within the dorsal raphe nucleus, implying a correlation between NFT counts and rate of progression of disease as all but 3 patients had severe dementia. Significantly, patients with AD complicated by major depression had fewer neurons at the mid level of the locus ceruleus and at the rostral level of the central superior nucleus in comparison with nondepressed patients. There was a trend suggesting greater loss of neurons at all levels of the locus ceruleus and dorsal raphe nucleus in depressed individuals.
Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease
Authors: Katzman Robert , Brown Theodore , Thal Leon J. , Fuld Paula A. , Aronson Miriam , Butters Nelson , Klauber Melville R. , Wiederholt Wigbert , Pay Marchy , Renbing Xiong , Ooi Wee Lock , Hofstetter Richard , Terry Robert D.
Published: January 2005

Longitudinal studies of subjects with autopsy‐proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information‐memory‐concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD 3.6, SEM 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home. More importantly, the rate of change of the IMC test provides no evidence for a difference between early‐onset and late‐onset Alzheimer's disease. The average rate of change on the IMC and its variance can be used as the basis for designing studies of drugs or procedures that might alter the course of Alzheimer's disease.
Effects of chronic phenobarbital exposure on cultured mouse spinal cord neurons
Authors: Serrano Elba E. , Kunis David M. , Ransom Bruce R.
Published: January 2005

The anticonvulsant phenobarbital (PB), at concentrations of 20, 40, and 90 μg/ml, was chronically applied to cell cultures of mouse spinal cord from day 2 or day 14 after initial plating, and the effects of this exposure on neuronal density and morphological characteristics were determined. Neuronal morphological characteristics were analyzed quantitatively following intracellular injection of the fluorescent dye Lucifer yellow. Cultures exposed to PB for 6 weeks, from day 14 after plating, showed concentration‐dependent reductions in neuronal density; both large and small neurons were equally affected. PB exposure also reduced dendritic branching frequency, and the length of dendrites, of remaining large neurons. A higher percentage of these neurons had a bipolar branching pattern than was normally the case. Neurons in cultures exposed to PB from day 2 after plating, compared with those exposed from day 14, showed significantly less alteration in terms of density and morphological characteristics. Effects on neuronal morphological characteristics increased with duration of drug exposure. Equimolar concentrations of barbituric acid produced effects similar to those produced by PB. Chronic exposure to PB adversely affects survival and morphological characteristics of mammalian central neurons grown in cell culture. Curiously, exposure from the time of initial plating appears to be less deleterious than exposure initiated 2 weeks later. To the extent that neuronal development in vitro can be compared to the situation in vivo, these results, and those of other investigators, raise concerns about long‐term exposure of the developing human nervous system to PB.
Hexosaminidase a deficiency manifesting as spinal muscular atrophy of late onset
Authors: Karni Avi , Navon Ruth , Sadeh Menachem
Published: January 2005

Proximal lower limb weakness and fasciculations were the only clinical manifestations of hexosaminidase A (Hex A) deficiency in a 39‐year‐old woman. Hex A activity in serum and leukocytes was 0 to 4% by standard heat inactivation fluorogenic substrate methods, and 5% when Hex A isoenzymes were fractionated by diethyl‐aminoethanol cellulose chromatography. Computed tomography of the brain showed cerebellar atrophy. We suggest that Hex A activity studies be done in patients with typical as well as a typical spinal muscular atrophy.
Successful treatment of cherry red spot—myoclonus syndrome with 5‐hydroxytryptophan
Authors: Gascon Generoso , Wallenberg Bradford , Daif Abdul Khadair , Ozand Pinar
Published: January 2005

A 14‐year‐old Saudi boy with cherry red spot‐myo‐clonus syndrome and documented neuraminidase deficiency responded well to titrated doses of 5‐hydroxy‐tryptophan as an add‐on treatment.
Paraneoplastic cerebellar degeneration: Clinical‐immunological correlations
Authors: Anderson Neil E. , Rosenblum Marchc K. , Posner Jerome B.
Published: January 2005

Four different antineuronal autoantibodies have been identified in 23 of 47 patients with paraneoplastic cerebellar degeneration (PCD). The most common, an antibody against 34‐ to 38‐kDa and 62‐ to 64‐kDa protein antigens in the cytoplasm of Purkinje cells, was found in 18 patients. It is a highly specific Marchker for a severe stereotypical subacute pancerebellar syndrome of truncal and appendicular ataxia, dysarthria, and nystagmus in women with cancer (usually ovarian or breast carcinoma). Different anti‐Purkinje cell antibodies (APCA) were found in 2 other patients with PCD. With two possible exceptions, an APCA was not found in patients with other neurological diseases, with cancer not associated with neurological symptoms, or in normal subjects. Antibodies reactive with neuronal nucleoproteins were identified in 3 other patients with PCD: an antibody that recognized 35‐ to 40‐kDa neuronal antigens was found in 2 women with small‐cell lung carcinorma, while an antibody in a woman with breast carcinoma identified 53‐ to 61‐kDa and 79‐ to 84‐kDa antigens. Detection of an antineuronal antibody in a patient without known cancer should prompt a careful search for a tumor at a site appropriate to the antibody type.
Neurofibrillary tangles in cholinergic pedunculopontine neurons in Alzheimer's disease
Authors: Mufson Elliott J. , Mash Deborah C. , Hersh Louis B.
Published: January 2005

The cholinergic neurons located within the pedunculopontine nucleus (Ch5) of patients with Alzheimer's disease (AD; n = 15), Parkinson's disease (PD; n = 2), and neurologically normal (n = 6) subjects were visualized immunohistochemically using choline acetyltransferase, pharmacohistochemically using acetylcholinesterase, or by reduced histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d). Each histochemical procedure localized a well‐delineated, compact lateral group and a more diffuse medial group of neurons within the pedunculopontine nucleus. Co‐localization experiments revealed that all three enzymes Marchked the same population of cholinergic neurons. The extent of pathological alterations associated with the cholinergic neurons within the compact lateral sector of the pedunculopontine nucleus was examined in sections that reacted for NADPH‐d, counterstained with thioflavin‐S. The average number of neurofibrillary tangles within this portion of the pedunculopontine nucleus was 25.4 (range 0–70) in patients with AD, 1.5 (range 1–2) in those with PD, and 1.2 (range 0–4) in aged control subjects. Of the total number of neurofibrillary tangles counted in AD cases, 72.7% were end‐stage ghosts and 27.3% were tangle‐bearing neurons. The pathological alteration of cholinergic neurons of the compact lateral aspect of the pedunculopontine nucleus may play a role in some of the behavioral features characteristic of AD.
Kearns‐sayre syndrome: Biochemical studies of mitochondrial metabolism
Authors: Martens M. E. , Peterson P. L. , Lee C. P. , Nigro M. A. , Hart Z. , Glasberg M. , Hatfield J. S. , Chang C. H.
Published: January 2005

Examination of oxidative metabolism in mitochondria isolated from quadriceps skeletal muscle biopsy specimens of 4 patients with Kearns‐Sayre syndrome has shown that the mitochondria were tightly coupled, with maximal respiratory rates depending on the presence of adenosine diphosphate (ADP), Ca2+, or uncoupler. The state 3 respiratory rates with nicotinamide adenine dinucleotide (NAD)—linked substrates and succinate were much lower than those of control subjects. The cytochrome oxidase activities (measured with ascorbate + phenazine methosulfate as substrates) were also Decemberreased, but this segment of the respiratory chain was not rate‐limiting for succinate or NAD‐linked substrate oxidation. Analyses of the steady‐state reduction kinetics of the respiratory chain carriers revealed that the rate‐limiting step of the impaired respiration with succinate or NAD‐linked substrates lies between the c cytochromes and cytochrome oxidase. Measurement of the total substrate‐reducible (at anaerobiosis) and chemically reducible levels of the cytochromes in mitochondria from 3 patients showed a severe deficiency of cytochrome a + a3 and an excess of the c cytochromes. To our knowledge, this is the first instance in which a mitochondrial electron transfer defect and cytochrome oxidase deficiency has been shown to be associated with an excess of the c cytochromes.
The effect of postischemic blood glucose levels on ischemic brain damage in the rat
Authors: Voll C. L. , Auer R. N.
Published: January 2005

The effect of insulin‐induced hypoglycemia following 10.5 minutes of forebrain ischemia was studied in the rat. All groups received preischemic glucose loading (2 gm/kg) to promote brain infarction. Following completion of ischemia, rats received either 2 to 3 IU/kg (low‐dose group) or 8 to 20 IU/kg (high‐dose group) insulin. During the survival period, blood glucose concentrations were maintained in the ranges of 1.2 to 2.9 mM and 2.9 to 4.9 mM, respectively, for the low‐dose and high‐dose insulin groups. Control rats were given 2 gm/kg glucose immediately following ischemia. During the recovery period, until perfusion at 7 days, they were given glucose, 2 gm/kg, twice daily by intraperitoneal injection, and their drinking water was supplemented with 25% glucose. Mortality (p < 0.05) and postischemic seizure incidence (p < 0.01) were significantly reduced in the low‐dose insulin group compared to the control group. Mortality was increased in the high‐dose insulin group compared to the control group and was associated with an increased incidence of postischemic seizures. Neuropathological examination revealed no cortical infarction in the low‐dose or high‐dose insulin‐treated rats compared to a 60% incidence of cortical infarction in the control group. In addition, the high‐dose insulin‐treated group showed a significant reduction in striatal and hip‐pocampal CA1 selective neuronal necrosis compared to control rats with comparable survivals (p < 0.05). The findings suggest that postischemic blood glucose concentrations play an important role in modulating both ischemic infarction and selective neuronal necrosis.
Biological differences between ischemia, hypoglycemia, and epilepsy
Authors: Auer Roland N. , Siesjo Bo K.
Published: January 2005

Ischemia, hypoglycemia, and epilepsy have long been thought to produce similar or identical brain damage. Further more, these insults have been assumed to be additive in their damaging effects. These notions have been based on neuropathological observations in the hippocampus and cerebral cortex, and on the tenet that energy failure (ischemia. hypoglycemia) and increased demand for energy (epilepsy) similarly give rise to selective neuronal neuronal mecrosis Recently, other bases for considering these three insults identical have grown out of observations that loss of calcium homeostasis is common to all and that an excitotoxic mechanism of selective neuronal necrosis exists in all three conditions. Fundamental differences between ischemia, hypoglycemia, and epilepsy include the underlying neurochemical changes induced, the neuronal revival times, the time course of neuronal death, the distribution of selective neuronal necrosis, and the likely excitotoxins released. Lactic acid accumulation, implicated in damage to the neuropil as well as to neuronal cell bodies, also occurs to different degrees and in different distributions in the three conditions. The degree and distribution of pannecrosis is thus also different in ischemia, hypoglycemia, and epilepsy.
Motor vehicle crashes in dementia of the alzheimer type
Authors: Friedland Robert P. , Koss Elisabeth , Kumar Anand , Gaine Sean , Metzler Diane , Haxby James V. , Moore Angela
Published: January 2005

To assess the occurrence and related features of motor vehicle crashes in patients with dementia of the Alzheimer type (DAT) we studied 30 patients who had been followed longitudinally and 20 healthy age‐matched control subjects. Data were gathered from first‐degree relatives who had lived with the subjects for the previous 5 years or more. Fortyseven percent of the DAT patients incurred at least one crash while they were driving, whereas only 10% of the control subjects had had a crash in the previous 5 years. The odds ratio for crashes in the DAT group was 7.9 (p < 0.01). Moreover, in 77% of DAT patients, a deterioration in driving performance was noted, and 63% of the patients had stopped driving. However, only 42% of the DAT patients who stopped driving did so before a crash occurred. Mean illness duration was 4.0 (± 1.8) years, and the mean Mini‐Mental Status Examination score was 19.9 (± 6.3) at the time of the first crash in the DAT group. The occurrence of crashes was not significantly correlated with dementia severity or with disease duration. These data suggest that the occurrence of driving crashes in patients with DAT is an important public health problem.
Phenotypic heterogeneity in familial alzheimer's disease: A study of 24 kindreds
Authors: Bird T. D. , Sumi S. M. , Nemens E. J. , Nochlin D. , Schellenberg G. , Lampe T. H. , Sadovnick A. , Chui H. , Miner G. W. , Tinklenberg J.
Published: January 2005

We report the clinical and neuropathological characteristics occurring in 180 demented individuals from 24 kindreds with familial Alzheimer's disease (FAD). Each family had at least two affected generations, and at least one autopsy or brain biopsy was compatible with the diagnosis of AD. Forty‐nine neuropathological specimens or reports were reviewed. Mean age of onset for the total group was 54.7 years ± 11.5, with a large range of 30 to 84 years. Mean age at death was 63.5 years ± 12.2, with a range of 46 to 85. Mean duration of disease was 8.8 years ± 4.4, with a range of 1 to 23 years. Six findings suggested phenotypic heterogeneity in FAD. (1) Five families represented an early age of onset group with mean onset at 42 years (range 30 to 51 years) and mean disease duration of 6.7 years. (2) Eight families represented a late onset group with mean onset at 68 years (range 59 to 78 years) and a mean duration of 8.5 years. (3) Seven families were of Volga German ancestry, all originating from the same two villages in Russia. Mean age of onset was 55.9 years (range 40 to 72 years), with a mean disease duration of 10 years. This group probably represents the genetic founder effect of an autosomal dominant gene for AD. (4) One family had the unusual characteristics of neurofibrillary tangles and granulovacuolar change but no amyloid plaques, a mean disease duration of more than 11 years, and a “schizophrenia‐like” onset. (5) One family with late onset also had clinical and pathological evidence for anterior horn cell disease. (6) Two autopsies in 1 family both showed remarkable rarefaction of myelin and expansion of perivascular spaces in centrum semiovale (état criblé), with marked leptomeningeal and cortical amyloid angiopathy, distinct from the other FAD brains. It remains to be determined whether the clinical and pathological differences between these families represent genetic heterogeneity at the biochemical or molecular level.
Clinical significance of cerebrospinal fluid tests for neurosyphilis
Authors: Davis Larry E. , Schmitt Joseph W.
Published: January 2005

From 1978 to 1987, 1,665 cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption (CSF‐FTA‐ABS) tests were performed as the screening procedure for neurosyphilis. The CSF samples from 48 patients were reactive, and the medical history and results of the CSF–Venereal Disease Research Laboratory test (CSF‐VDRL) for syphilis for 38 of these patients were reviewed. Likely active neurosyphilis was diagnosed if the patient had a reactive CSF‐FTA‐ABS test, recent onset of neurological signs consistent with neurosyphilis, abnormal CSF, and no other recognized cause for the neurological illness. Fifteen patients were so classified. Four had a reactive CSF‐VDRL test. The specificity of the CSF‐VDRL in diagnosing likely active neurosyphilis was 100%, but the sensitivity was only 27%. The insensitivity of the CSF‐VDRL test limits its usefulness as a screening test for neurosyphilis. The CSF‐FTA‐ABS test appears more sensitive for screening but is less specific than the CSF‐VDRL test in distinguishing currently active neurosyphilis from past syphilis. These findings imply that clinical judgment is still essential in establishing the diagnosis of active neurosyphilis.
Speech manifestations in lateralization of temporal lobe seizures
Authors: Gabr M. , Lüders H. , Dinner D. , Morris H. , Wyllie E.
Published: January 2005

To evaluate the role of speech manifestations in lateralization of temporal lobe seizures, we reviewed videotapes of 100 complex partial seizures in 35 patients who underwent temporal lobectomy for intractable epilepsy. All patients had prolonged electroencephalographic video monitoring with scalp and subdural electrodes, and their speech dominance was determined with an intracarotid amobarbital test. Speech manifestations were observed in 79 seizures and were classified as vocalization, normal speech, or abnormal speech. Vocalization of sounds without speech quality occurred ictally in 48.5% of patients. Normal speech (identifiable speech) occurred ictally in 34.2% of patients. Abnormal speech (speech arrest, dysphasia, dysarthria, and nonidentifiable speech) occurred in 51.4% of patients, either ictally or postictally. Of all the above speech manifestations, only postictal dysphasia and ictal identifiable speech had significant lateralizing value: 92% of patients with postictal dysphasia had their seizures originating from the dominant temporal lobe (p < 0.001), and 83% of those with ictal identifiable speech had their seizures from the nondominant side (p = 0.013). This study shows that speech manifestations are common in complex partial seizures of temporal lobe origin and can provide an excellent clinical tool for lateralization of seizure onset.
The prevalence of primary sjögren's syndrome in a multiple sclerosis population
Authors: Noseworthy J. H. , Bass B. H. , Vandervoort M. K. , Ebers G. C. , Rice G. P. A. , Weinshenker B. G. , McLay C. J. L. , Bell D. A.
Published: January 2005

A central nervous system illness closely resembling multiple sclerosis has been described in patients with primary Sjögren's syndrome. From these reports, the estimated prevalence of this syndrome could be similar to that of multiple sclerosis in a high‐frequency area. We evaluated 192 consecutive patients in our multiple sclerosis clinic to determine if such cases had gone unrecognized. We did not find any patients with clinical or serological evidence of primary Sjögren's syndrome. We conclude that it is rare for neurological manifestations of Sjögren's syndrome to mimic multiple sclerosis in our population.
Immunocytochemical characterization of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism‐dementia of guam
Authors: Shankar Susarla K. , Yanagihara Richard , Garruto Ralph M. , Grundke‐Iqbal Inge , Kosik Kenneth S. , Gajdusek D. Carleton
Published: January 2005

Cryostat‐cut sections of formalin‐fixed and unfixed hippocampus from 23 Guamanian Chamorros with clinically and neuropathologically verified amyotrophic lateral sclerosis (ALS) (8 cases) and parkinsonism‐dementia (PD) (15 cases) and from 12 neurologically normal Guamanians (5 with and 7 without neurofibrillary degeneration) were evaluated by the immunoperoxidase technique, using monoclonal antibodies against phosphorylated neurofilament, human fetal microtubule‐associated protein tau, and paired helical filaments. On immunostaining, all three antibodies showed intracellular tangles in the hippocampal neurons of patients with ALS, patients with PD, and in neurologically normal Guamanians with neurofibrillary pathology, but the correlation of immunostaining between these antibodies was not absolute. Extracellular or ghost tangles were immunostained only with the antibody against paired helical filaments. Our immunocytochemical data indicate that the antigenic composition of neurofibrillary tangles in Guamanian ALS and PD is similar to that of Alzheimer's disease, suggesting a common pathogenetic pathway for neurofibrillary tangle formation in these neurodegenerative disorders.
Transient neonatal hyperglycinemia
Authors: Schiffmann Raphael , Kaye Edward M. , Willis John K. , Africk Diane , Ampola Mary
Published: January 2005

Two patients with neonatal seizures and subsequent normal neurological development were found to have nonketotic hyperglycinemia. In both patients, hyperglycinemia resolved at 6 weeks of age. After cerebrospinal fluid glycine levels were normalized, the seizures stopped completely in one child and were markedly improved in the other. The possible mechanisms for the hyperglycinemia are discussed.
Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital
Authors: Twyman Roy E. , Rogers Carl J. , Macdonald Robert L.
Published: January 2005

The anticonvulsant activity of diazepam and phenobarbital may be mediated in part by enhancement of inhibition involving γ‐aminobutyric acid (GABA). While both diazepam and phenobarbital increase GABA receptor chloride current, they may have different mechanisms of action, since they bind to different sites on the GABA receptor—chloride channel complex. We used the patch clamp technique to compare the effects of diazepam and phenobarbital on single GABA receptor currents. Outside‐out patches were obtained from mouse spinal cord neurons grown in cell culture for 2 to 4 weeks. GABA (2 μM) evoked single channel currents that occurred as single brief openings or in bursts of multiple openings. Diazepam (20 nM) and phenobarbital (500 μM) both increased the GABA receptor current by increasing mean open time without altering channel opening frequency. However, the temporal grouping of openings into bursts suggested that the enhancement occurred via different mechanisms. Diazepam increased the frequency of bursting GABA receptor currents with minimal effect on the duration of bursts. Phenobarbital increased the duration of bursting GABA receptor currents without altering the frequency of bursts. These results suggest that diazepam binds to a site that may enhance single channel burst frequency by increasing the affinity of GABA binding, while phenobarbital may stabilize the bursting open state of the channel by binding to a different modulatory site at or near the chloride channel.
Decreased adhesiveness of alzheimer's disease fibroblasts: Is amyloid β‐protein precursor involved?
Authors: Uéda Kenji , Cole Gregory , Sundsmo Mary , Katzman Robert , Saitoh Tsunao
Published: January 2005

The adhesiveness of fibroblasts derived from Alzheimer's disease (AD) patients to a plastic substratum was assessed as the proportion of cells attached to a plastic dish bottom after a 30‐minute incubation in culture medium of cells dissociated in ethylenediaminetetraacetic acid and was compared with the adhesiveness of normal fibroblasts from non‐AD controls. It was found that the normal fibroblasts adhered better to plastic than did AD cells. This reduced adhesiveness was observed in fibroblasts derived from both sporadic and familial AD patients. Because of the possible involvement of amyloid β‐protein precursor (ABPP) in the process of cellular adhesion, the amount of ABPP messenger RNA was measured in these fibroblasts and was found to be decreased in the familial AD fibroblasts, although not in cells from sporadic AD patients. Furthermore, there were fewer molecules detected by an anti‐ABPP antibody in conditioned media from familial AD fibroblasts as compared with media from control fibroblasts. Therefore, although it is possible that the reduced adhesiveness of familial AD fibroblasts may result from genetic deficits in ABPP gene expression, the reduced adhesiveness of sporadic AD fibroblasts most likely results from certain deficits in molecules other than the ABPP.
Lambert‐eaton myasthenic syndrome: Immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity
Authors: Lang B. , Vincent A. , Murray N. M. F. , Newsom‐Davis J.
Published: January 2005

We compared the effects of Lambert‐Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small‐cell lung carcinoma (SCLC) on voltage‐gated (K+‐stimulated) 45Ca2+ flux in cell lines derived from a human SCLC (MAR10) and from a rat pheochromocytoma (PC12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2+ flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC‐LEMS IgG (0.38 nmol/106 cells; p < 0.001) or non‐SCLC‐LEMS IgG (0.35 nmol/106 cells; p < 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/106 cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC‐associated LEMS.
Transient ocular motor paresis associated with acute internal carotid artery occlusion
Authors: Wilson W. Bruce , Leavengood John M. , Ringel Stephen P. , Bott Allen D.
Published: January 2005

While sudden monocular blindness and occlusion of the central retinal artery associated with acute thrombosis of the internal carotid artery are well reported, concurrent unilateral ophthalmoparesis is not. We studied 3 adult men who did not have other major signs of vascular disease but who exhibited the complete syndrome. The initial paresis of the oculomotor, trochlear, and abducens nerves varied in each individual and slowly cleared over days to weeks in all, but vision did not return in any. Each had mild‐to‐moderate signs of hemispheric dysfunction. In each, the thrombus extended from the origin of the internal carotid to its intracranial bifurcation into the anterior and middle cerebral arteries. It also occluded the proximal one‐half to two‐thirds of the ophthalmic artery. None had evidence of vasculitis or compromise of the posterior circulation.
Development of dementing illnesses in an 80‐year‐old volunteer cohort
Authors: Katzman R. , Aronson M. , Fuld P. , Kawas C. , Brown T. , Morgenstern H. , Frishman W. , Gidez L. , Eder H. , Ooi W. L.
Published: January 2005

We have prospectively followed over a 5‐year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty‐six (an incidence of 3.53 per 100 person‐years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person‐years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5%f of the cohort who made zero to two errors on a 33‐item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80‐year‐olds who are at low risk for AD and a smaller cohort at very high risk.
The effect of intraocular 6‐hydroxydopamine on retinal processing of primates
Authors: Ghilardi Maria Felice , Marx Marcia S. , Bodis‐Wollner Ivan , Camras Carl B. , Glover Andrew A.
Published: January 2005

In previous studies, we showed that in the monkey, systemically administered N‐methyl, 4‐phenyl, 1‐2‐3‐6 tetrahydropyridine (MPTP) produces a chronic parkinsonian syndrome accompanied by spatial frequency‐dependent abnormalities in both the pattern electroretinogram and visual evoked potential. We describe the effect of intravitreally administered 6‐hydroxydopamine (6‐OH‐DA) on the pattern electroretinogram and pattern visual evoked potential of 3 aphakic monkeys. Because of the aphake condition, several complexities of intravitreal injection of 6‐OH‐DA could be avoided. Nevertheless, following 6‐OH‐DA treatment, both the phase and the amplitude of pattern electroretinogram and pattern visual evoked potential became abnormal. This abnormality was most pronounced for the higher spatial frequencies (2.5 and 3.5 cycles per degree), whereas lower spatial frequencies (0.5 and 1.2 cycles per degree) were less impaired. The effects of systemically administered MPTP on pattern electroretinogram and pattern visual evoked potential are similar to the effects of intravitreal injections of 6‐OH‐DA, suggesting that a retinal catecholaminergic system plays an important role in pattern vision of primates.
Catecholamine depletion produces irrepressible saccadic eye movements in normal humans
Authors: Tychsen Lawrence , Sitaram N.
Published: January 2005

To determine the effect of catecholamine depletion on ocular motor pathways in humans, we studied the eye movements of 3 normal subjects who received the drug metyrosine (alpha‐methylparatyrosine). This drug temporarily depleted dopamine and norepinephrine, as measured by a reduction in the metabolite, 3‐methoxy‐4‐hydroxy‐phenylethyleneglycol (MHPG). Saccadic, pursuit, and vestibulo‐ocular eye movements were recorded using infrared oculography with subjects both on placebo and on metyrosine. The most consistent effect observed with metyrosine was an increase in the amplitude and frequency of saccadic intrusions during fixation and pursuit. Two of the 3 subjects also had shortened time constants for the vestibulo‐ocular reflex, attributable in part to the sedative effect of catecholamine depletion. The increase in saccadic intrusions implies that catecholamines modulate the activity of a subpopulation of suppressor motor neurons in the human brainstem.