bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities of peripheral nerve in patients with human immunodeficiency virus infection
Authors: Mah Vei , Vartavarian Luiza M. , Akers Marchi‐Anne , Vinters Harry V.
Published: January 2005

The purpose of this study was to assess systematically morphology of peripheral nerves from patients with human immunodeficiency virus infection (acquired immunodeficiency syndrome [AIDS] and AIDS‐related complex) examined at autopsy. Sural nerve specimens were taken from 25 patients (mean age 44 years) and evaluated by routine procedures used in our laboratory. In 13 cases no detectable abnormality was seen. Twelve patients (48%) showed loss of myelinated fibers with disproportionately greater loss of large myelinated fibers. Three of these patients showed severe myelinated fiber loss; 2 had no documented symptoms and no other known predisposing factors for a peripheral neuropathy. Changes suggestive of wallerian degeneration were occasionally seen, as were epineurial and endoneurial inflammatory infiltrates. Segmental demyelination was not identified in any nerve examined. Electron microscopy revealed thickened basement membranes around small blood vessels, Schwann cells, and fibroblasts. Peripheral nerve abnormalities in patients with AIDS or ARC are frequent and their pathogenesis remains unclear.
The glucose transporter of the human brain and blood‐brain barrier
Authors: Kalaria Rajesh N. , Gravina Stephen A. , Schmidley James W. , Perry George , Harik Sami I.
Published: January 2005

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D‐glucose‐displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant < 1 μM. Maximal binding capacity was ∽ 7 pmol/mg protein in the cerebral cortex, ∽ 42 pmol/ mg protein in brain microvessels, and ∽ 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank‐order that correlated well with their known ability to cross the blood‐brain barrier; the only exception was 2‐deoxy‐D‐glucose, which had much higher affinity for the glucose transporter than the natural substrate, D‐glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of ∽ 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species.
Acetylcholinesterase‐rich pyramidal neurons in the human neocortex and hippocampus: Absence at birth, development during the life span, and dissolution in Alzheimer's disease
Authors: Mesulam M.‐Marchsel , Geula Changiz
Published: January 2005

Acetylcholinesterase‐rich pyramidal neurons in the human association neocortex and hippocampal formation are virtually absent early in life, become established by adolescence, and appear to increase in density during adulthood and perhaps even senescence. Analogous neurons are not detectable in the adult monkey brain. This Novemberel class of neurons may represent a uniquely human adaptation in primate evolution and may provide a neuroanatomical substrate for the mental development that occurs during the adult stages of life. These phylogenetically and ontogenetically progressive neurons are also Marchkedly vulnerable to degeneration in Alzheimer's disease.
Transverse sinus thrombosis in newborns: Clinical and magnetic resonance imaging findings
Authors: Baram Tallie Z. , Butler Ian J. , Nelson Marchvin D. , McArdle Craig B.
Published: January 2005

Neonatal transverse sinus thrombosis (TST) is considered a rare and severe sequela of birth injury. Clinical descriptions of this entity are few since most published series are postmortem studies. The advent of magnetic resonance imaging (MRI) allows recognition of TST ante mortem. We describe 4 full‐term infants with distinct clinical and neuroradiological features indicative of TST, which we suggest may be relatively common, with a wide spectrum of severity, including favorable outcome.
Serial magnetic resonance scanning in multiple sclerosis: A second prospective study in relapsing patients
Authors: Willoughby E. W. , Grochowski E. , Li D. K. B. , Oger J. , Kastrukoff L. F. , Paty D. W.
Published: January 2005

A prospective study of serial magnetic resonance (MR) scans of the brain was carried out every 2 weeks for 4 to 6 months in 9 patients with mild, clinically definite, relapsing/remitting multiple sclerosis (MS). Six of the 9 patients developed a total of 12 asymptomatic new lesions in various parts of the brain. In none of the patients were the changes on MR scan accompanied by relevant new neurological symptoms or signs. New MR lesions had a characteristic temporal profile, reaching a maximum size in approximately 4 weeks before gradually shrinking, usually leaving a small residual abnormality indistinguishable from chronic MS lesions. The frequent occurrence of new asymptomatic lesions indicates that MS may be a more active process even in mildly affected asymptomatic patients than has been previously realized. The results emphasize the potential importance of using MR scanning to measure disease activity in laboratory studies of MS and in the assessment of treatment, particularly in asymptomatic patients in the early stages. We suggest that the expanding and contracting new lesions are the basic or primary lesion in MS, that the characteristic demyelinated plaque is represented by the small residual area that these lesions shrink down to, and that the typical collection of scattered white matter lesions in chronic MS may represent the accumulated residua of dozens or more of these active lesions occurring over many years.
Cerebrospinal fluid biogenic amines and biopterin in rett syndrome
Authors: Zoghbi Huda Y. , Milstien Sheldon , Butler Ian J. , Smith E. O'Brian , Kaufman Seymour , Glaze Daniel G. , Percy Alan K.
Published: January 2005

We evaluated cerebrospinal fluid biogenic amine metabolites in 32 patients with Rett syndrome. Significant reductions were noted in the metabolites of norepinephrine, dopamine, and serotonin, as compared with controls of similar age (p < 0.00l, p < 0.001, and p < 0.05, respectively). Tetrahydrobiopterin is an essential cofactor and may be rate‐limiting for the synthesis of catecholamines and serotonin. Accordingly, total cerebrospinal fluid biopterin was measured and found to be elevated in patients compared with controls (p < 0.002). These findings constitute the only biochemical changes detected in Rett syndrome so far.
Bilateral opercular polymicrogyria
Authors: Becker P. Scott , Dixon Ann M. , Troncoso Juan C.
Published: January 2005

Foix‐Chavany‐Marie syndrome (FCMS), or faciopharyngoglossomasticatory diplegia, is an uncommon syndrome that can result from vascular or developmental lesions of the anterior opercula bilaterally. We report the first pathological documentation of the developmental form of this disorder. Pathological examination revealed bilateral failure of opercular closure, opercular polymicrogyria, periventricular gray‐matter heterotopias, and absence of the septum pellucidum.
Carbamazepine and its epoxide: Relation of plasma levels to toxicity and seizure control
Authors: Theodore William H. , Narang P. K. , Holmes Mark D. , Reeves Pat , Nice Frank J.
Published: January 2005

We studied the relation of plasma levels of carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ‐E), and their ratio to drug toxicity and seizure control in 7 patients with complex partial seizures. CBZ‐E/CBZ increased with increasing CBZ levels and was higher when patients were taking phenytoin or valproic acid. There were weak correlations between CBZ, CBZ‐E levels, toxicity scores, and seizure control when patients were taking CBZ alone, but not when other drugs were given as well. There were no significant differences in the correlation with toxicity score or seizure frequency between CBZ, CBZ‐E, or their sum. Measurement of CBZ‐E levels did not provide additional information useful for monitoring clinical response to CBZ therapy.
The effects of a new tissue plasminogen activator analogue, Fb‐Fb‐CF, on cerebral reperfusion in a rabbit embolic stroke model
Authors: Phillips David A. , Fisher Marc , Smith Thomas W. , Davis Michael A. , Pang Roy H. L.
Published: January 2005

Early fibrinolytic therapy with full molecular tissue plasminogen activator (t‐PA) has been observed to be both angiographically and clinically effective when employed in animal stroke models. Preliminary clinical trials with t‐PA are in progress. It is possible to refine t‐PA by developing fragments or analogues of the drug. Using recombinant DNA technology in the Escherichia coli system, a t‐PA analogue consisting of the catalytic fragment of t‐PA and a dimer of the B fragment of staphylococcal protein A (Fb‐Fb‐CF) has been produced. Because this analogue has a long serum half‐life of 90 minutes, we employed Fb‐Fb‐CF in a rabbit cerebral embolic stroke model to assess its efficacy as a reperfusion agent. When given as a bolus to 10 animals 15 minutes after embolization, Fb‐Fb‐CF produced angiographic cerebral reperfusion in 48 ± 21 minutes (± SD), while in 8 saline‐treated controls, reperfusion was not observed at 180 minutes in any animal (p < 0.01). In another experiment reperfusion was demonstrated at 66 ± 32 minutes in 11 animals treated with Fb‐Fb‐CF 90 minutes after embolization as compared with 100 ± 25 minutes in 12 saline‐treated controls (p < 0.01). A small macroscopic hemorrhage within an infarct was seen in 1 Fb‐Fb‐CF‐treated animal in the 15‐minute experiment and in none of the controls. In the 90‐minute experiment, macroscopic hemorrhagic infarction was seen in 4 Fb‐Fb‐CF‐treated animals and in 3 controls. Plasma fibrinogen levels measured in the 15‐minute Fb‐Fb‐CF treatment group declined by 16% immediately after the Fb‐Fb‐CF bolus was administered and by 19% after 180 minutes. These data demonstrate that Fb‐Fb‐CF can rapidly reestablish cerebral perfusion with only modest reductions in plasma fibrinogen when given either 15 or 90 minutes after cerebral embolization.
Peripheral nerve vasculitis: Immune characterization of the vascular lesions
Authors: Kissel John T. , Riethman Joseph L. , Omerza Jennifer , Rammohan Kottil W. , Mendell Jerry R.
Published: January 2005

Quantitative immunohistochemical analyses were performed on 22 nerve biopsy specimens from patients with systemic vasculitis (n = 14) or isolated vasculitis of peripheral nerve (n = 8). In the vascular lesions the cellular infiltrates were composed primarily of T cells (71 ± 18%; mean ± SD) and macrophages (27 ± 17%), and the majority of the T cells (65 ± 20%) were cytotoxic/suppressor CD8 cells. B cells were seen in only 4 cases and constituted less than 2% of all cells. Natural killer cells and polymorphonuclear leukocytes were rare, and a leukocytoclastic response was not observed. Fourteen biopsy specimens had vascular deposits of immunoglobulins G and M and complement components C3 and C5b‐9 membrane attack complex, while 4 had only the latter. The fact that the immunoglobulin and complement deposits were seen only in vessels that had corresponding intense cellular infiltrates suggests an important, but perhaps not primary, role for immune complexes in causing the vascular lesions. Statistical analysis revealed striking similarities in the lesions of patients with isolated nerve vasculitis and those with systemic vasculitides, suggesting a common pathogenic mechanism. Collectively, our observations suggest an important role for a T‐cell‐dependent cell‐mediated process as a primary mechanism of vessel injury in peripheral nerve vasculitis.
Influence of cerebral hemodynamics on stroke risk: One‐year follow‐up of 30 medically treated patients
Authors: Powers William J. , Tempel Lee W. , Grubb Robert L
Published: January 2005

The importance of hemodynamic factors in the pathogenesis and treatment of ischemic cerebrovascular disease is not clear. We have investigated the relationship between cerebral hemodynamics and the subsequent risk of stroke in 30 medically treated patients with symptomatic occlusion or greater than 75% intracranial stenosis of the carotid arterial system. Positron emission tomography (PET) was used to evaluate the regional hemodynamic status of the cerebral circulation. Clinical follow‐up to 1 year post‐PET was available for all patients. The incidence at 1 year of all strokes was 1/9 for patients with normal hemodynamics and 1/21 for patients with abnormal hemodynamics. The 1‐year incidence of ipsilateral ischemic stroke was 1/9 for hemodynamically normal patients and 0/21 in the abnormal group. The 21 patients in the abnormal group fulfilled entry criteria for the Extracranial‐Intracranial Bypass Trial. The 0/21 incidence of ipsilateral ischemic stroke at 1 year was compared with the 1‐year rate of 0.109 for the 714 medically treated patients from the Bypass Trial. We were able to reject with better than 90% certainty (p = 0.089) the hypothesis that our sample of patients came from a population with an ipsilateral ischemic stroke rate of 0.109 or greater. Thus, in this small sample, we found no evidence that PET evidence of abnormal cerebral hemodynamics identifies a subgroup of patients at higher risk for early stroke if treated medically with antithrombotic drugs.
Controlled release of dopamine from a polymeric brain implant: In vivo characterization
Authors: During Matthew J. , Freese Andrew , Sabel Bernhard A. , Saltzman W. Mark , Deutch Ariel , Roth Robert H. , Langer Robert
Published: January 2005

Intracerebral microdialysis was used to evaluate the long‐term in vivo release of dopamine from ethylene‐vinyl acetate (EV Ac)‐dopamine copolymer matrix discs for up to 65 days following striatal implantation. Dopamine release occurred through a single cavity present on one side of the disc, which was otherwise fully coated with an additional, impermeable layer of EV Ac. At 20 days following implantation of the device, extracellular concentrations of dopamine within the striatum reached micromolar levels, over 200‐fold greater than control values. Release of dopamine was shown to be stable and maintained for the 2‐month duration of the experiment. Histological examination confirmed the biocompatible nature of the implant. There are potential applications of this technology to the treatment of Parkinson's disease and other neurological and psychiatric disorders.
Human choroid plexus cells can be latently infected with human immunodeficiency virus
Authors: Harouse Janet M. , Wroblewska Zofia , Laughlin Mark A. , Hickey William F. , Schonwetter Barry S. , Gonzalez‐Scarano Francisco
Published: January 2005

The human immunodeficiency virus (HIV) penetrates the central nervous system, particularly the cerebrospinal fluid, early in the course of HIV infection, and may cause a progressive encephalopathy in patients prior to the development of the acquired immunodeficiency syndrome. Neither the specific mechanism for penetration of the virus into the central nervous system nor the pathophysiological basis for these abnormalities is well understood. We cultured cells from the choroid plexus of 3 individuals who died of causes unrelated to the acquired immunodeficiency syndrome and demonstrated that these cells can be infected with type 1 HIV. Infection of cells of the choroid plexus may provide an initial route of entry of HIV into the cerebrospinal fluid and, together with the macrophage, a route of entry into the brain.
Gaze distractibility in wilson's disease
Authors: Lennox Graham , Jones Richard
Published: January 2005

We describe the case of a patient with Wilson's disease who was first seen with distractibility of gaze fixation. Clinical and magnetic resonance imaging studies suggest that the disorder was probably due to frontal lobe involvement.
Simple and choice reaction time in patients with human immunodeficiency virus infection
Authors: Perdices Michael , Cooper David A.
Published: January 2005

The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody‐seronegative controls on simple (SRT) and choice (CRT) reaction time tasks. Patients were classified into 3 groups according to Centers for Disease Control clinical criteria. There were 18 patients who had acquired immunodeficiency syndrome (AIDS), 18 who had AIDS‐related complex (ARC), and 20 who were HIV antibody‐seropositive but otherwise asymptomatic (HIV‐Ab+). The SRT task consisted of 5 trials, each containing 10 target stimuli. The CRT task consisted of 10 trials, each containing 5 target stimuli randomly interspersed with 5 nontarget stimuli. The mean response latency of each of the patient groups on the SRT task was not significantly different from that of controls. However, the performance of patients with AIDS or ARC on the CRT task was significantly lower than that of controls, whereas that of HIV‐Ab+ patients was not. Analysis of the quality of RT task performance also indicated that the impairment of processing efficiency at higher levels of task difficulty reflected a disruption of processing prior to the response selection stage.
Continuous and intermittent levodopa differentially affect basal ganglia function
Authors: Juncos Jorge L. , Engber Thomas M. , Raisman Rita , Susel Zvi , Thibaur Florence , Ploska Alain , Agid Yves , Chase Thomas N.
Published: January 2005

The effects of continuous and intermittent levodopa treatment on behavioral and biochemical indexes of basal ganglia function were compared in rats with unilateral 6‐hydroxydopamine lesions of the nigrostriatal dopamine pathway. Animals treated for 30 days with intermittent levodopa exhibited behavioral sensitization manifested by an enhanced rotational response to apomorphine; the rotational response of rats treated with an equivalent dose of levodopa by continuous infusion did not differ from that of saline‐treated controls. Dopamine receptor up‐regulation in the denervated striatum relative to the intact striatum was statistically significant for D1 but not D2 receptors: This asymmetry in dopamine receptor levels was diminished following intermittent levodopa treatment. Glutamic acid decarboxylase activity, modestly elevated in all groups in the denervated striatum relative to the intact striatum, increased substantially over control values bilaterally as a result of intermittent, but not continuous, levodopa treatment. These findings suggest a relation between the schedule of chronic levodopa administration and the development of behavioral sensitization, possibly as a consequence of alterations in neuronal systems located downstream from striatal dopamine receptors. The behavioral sensitization induced by chronic, intermittent dopaminomimetic treatment may serve as a model for motor fluctuations in Parkinson's disease.
Swellings of proximal axons in a case of motor neuron disease
Authors: Sasaki Shoichi , Maruyama Shoichi , Yamane Kiyomi , Sakuma Hideo , Takeishi Makoto
Published: January 2005

Serial semithin sections of lumbar anterior horn cells from a patient with rapidly progressive sporadic motor neuron disease were searched for direct connections between swellings of neuronal processes and perikarya. Focal swellings of the proximal axons were not uncommonly seen to be connected directly to perikarya. These swellings varied in shape and size and some were identified as spheroids. Most of the cell bodies connected with swellings showed otherwise normal architecture. These observations suggest that the focal swellings of proximal axons, particularly the distal portion of the initial segment and the first internode of the myelinated axon, indicate an early pathological change, and may represent functionally and morphologically vulnerable sites.
Stroke risk and age do not predict behavioral activation of brain blood flow
Authors: Ewing James R. , Brown Gregory C. , Gdowski James W. , Do Robert Simkins , Levine Steven R. , Welch K. M. A.
Published: January 2005

Twenty‐four neurologically normal subjects, 12 in their twenties and 12 in their sixties, were included in a protocol that studied the relationship of resting cerebral blood flow and cerebral blood flow activation by neuropsychological testing to age and stroke risk factors. Both age and a stroke risk index were predictive of a reduced resting cerebral blood flow. Despite this, cerebral blood flow activation relative to resting flow was preserved. Subclinical lesions of deep white matter are proposed to explain the apparently paradoxical result that resting cerebral blood flow is decreased by factors that damage cerebral vessels, while cerebral vascular reactivity is unimpaired.
Postmortem detection of measles virus in non‐neural tissues in subacute sclerosing panencephalitis
Authors: Brown Hannah R. , Goller Nancy L. , Rudelli Raoul D. , Dymecki Jerzy , Wisniewski Henryk M.
Published: January 2005

Subacute sclerosing panencephalitis, a rare, progressive, fatal central nervous system disease of children, is caused by measles virus. Clinical signs occur months to several years after recovery from acute measles infection. It is not known where the virus persists while the disease is inapparent. Involvement of organs outside the central nervous system has rarely been documented. To search for possible peripheral reservoirs of measles virus we used in situ hybridization to probe for measles virus RNA and immunocytochemical studies to localize measles virus antigens in a variety of organs taken at autopsy from confirmed cases of subacute sclerosing panencephalitis. Seven of 9 cadavers were found to contain measles virus RNA or antigens, or both, in at least one location outside the central nervous system. These sites included lymphoid organs such as thymus, spleen, lymph nodes, and tonsil, suggesting a role for lymphocytes in disease pathogenesis. Virus was also detected in kidney, lung, and glandular tissues such as pancreas, adrenal, and pituitary. These reservoirs may provide the antigenic stimulus leading to the elevated humoral response characteristic for subacute sclerosing panencephalitis.
Localization of immunoreactive thymosin α1 in astrocytes of normal human brain
Authors: Su Yuan‐liang , Loon Ho Kang , Dalakas Marinos C. , Mutchnick Milton G.
Published: January 2005

We employed an immunocytochemical method to examine human brain for the presence of immunoreactive thymosin α1 (Tα1), a peptide derivative of thymic tissue, using a well‐characterized antiserum. For cell identification, serial sections were stained with antisera to thymosin β4(Tβ4), another thymic peptide that identifies oligodendrocytes, and with anti‐glial fibrillary acidic protein (GFAP) antiserum that stains astrocytes in a double‐staining technique using avidin‐biotinylated horseradish peroxidase or avidin‐biotinylated alkaline phosphatase complex. Antiserum to Tα1 stained the cell body, but not the processes, of GFAP‐positive astrocytes, suggesting that Tα1 is a common antigen shared between thymus and astrocytes. Because Tα1 and its precursor molecule play a role in cell proliferation and immunomodulation, our findings could explain the role of astrocytes in certain central nervous system diseases.
Direct evidence for calcium‐induced ischemic and reperfusion injury
Authors: Uematsu Daisuke , Greenberg Joel H. , Reivich Martin , Hickey William F.
Published: January 2005

Changes in cytosolic free calcium ([Ca2+]i) in the cat cortex were measured in vivo by indo‐1 fluorometry during cerebral ischemia and reperfusion and were correlated to the histopathological ischemic changes. These changes were most pronounced in stroke cases with an increase in [Ca2+]i throughout the ischemic and reperfusion periods. Cases without a [Ca2+]i increase showed no histopathological change in the cortical gyrus in which [Ca2+]i was measured. The data support the hypothesis that an increase in [Ca 2+]i during cerebral ischemia and reperfusion leads to neuronal damage.
Neuropathological distinction between Parkinson's dementia and Parkinson's plus Alzheimer's disease
Authors: de la Monte Suzanne M. , Wells Sarah E. , Hedley‐Whyte E. Tessa , Growdon John H.
Published: January 2005

The distinctive clinical features of dementia in Parkinson's disease (PDD) and Parkinson's plus Alzheimer's disease (PD + AD) suggest different patterns of cerebral atrophy in these conditions. To determine the pathoanatomical substrates of dementia in PDD and PD + AD, morphometric analysis of 5 standardized coronal slices was used to identify volumetric changes in cerebral tissue. In PDD (n = 4) there were 9 to 23% reductions in cross‐sectional area of cerebral cortex, a 38% loss of tissue in the globus pallidus + putamen, and an 18% reduction in area of the amygdala, whereas in PD + AD (n = 6) there was severe global atrophy of the cerebral cortex (27–29% reductions) moderate atrophy of white matter (10–19% reductions), and 40% reductions in areas of globus pallidus + putamen and the amygdale relative to neuropathologically intact controls (n = 14). Immunostaining with anti‐glial fibrillary acidic protein disclosed significant gliosis of all four major subdivisions of neocortex in PD + AD and gray matter of the caudate, putamen, globus pallidus, and thalamus in both PDD and PD + AD relative to controls. The findings suggest that dementia in PDD is mainly subcortical in origin and due to neuronal degeneration in basal ganglia, the amygdale, and thalamus. In PD + AD the same pattern and degree of subcortical degeneration is evident, but there are clearly superimposed lesions involving cortical neurons and long projection fibers coursing through cerebral white matter that most likely account for the distinctive manifestations of dementia in this condition compared with PDD.
Limbic P3 potentials, seizure localization, and surgical pathology in temporal lobe epilepsy
Authors: Puce Aina , Kalnins Renate M. , Berkovic Samuel F. , Bladin Peter F.
Published: January 2005

Limbic P3 event‐related potentials were recorded from mesial temporal electrodes implanted for presurgical investigation in 70 patients with intractable focal seizures. IN 46 (81%) of 57 patients with unilateral temporal lobe epilepsy, the limbic P3 potential was absent or rudimentary ipsilateral to the seizure focus and a robust P3 potential was always elicite from the nonepileptogenic temporal lobe. Bilateral P3 potentials were recorded in 6 patients (10%) with unilateral temporal lobe epilepsy. In the remaining 5 patients in the group with unilateral temporal lobe epilepsy, results showed P3 bilaterally absent (2 patients), P3 present in a unilateral investigation (1 patient), P3 absent contralateral to the seizure focus (1 patient), and technically unsatisfactory recordings (1 patient). Bilaterally absent P3 potentials were noted in 2 patients with bilateral temporal lobe epilepsy. In 6 patients with technically adequate P3 studies and extratemporal seizures, bilaterally present P3 potentials were noted. Sensitivity and specificity of P3 absence as a predictor of an epileptoghenic temporal lobe were 87% and 95%, respectively. Tissue specimens of the hippocampus were available in 22 patients (43%). Thirteen hippocampi showed sclerosis, all of which were associated with unilaterally absent P3 potentials. Nine hippocampi were normal (5 patients with the P3 absent, 4 with P3 present). Sensitivity and specificity of an absent limbic P3 as a function of hippocampal pathological findings were 100% and 44%, respectively. Absent limbic P3 potentials in temporal lobe epilepsy thus indicate strucutal or functional hippocambal abnormality and may add important information in presurgical evaluation with depth electrodes of patients who have temporal lobe epilepsy.
Galactosylceramide: A reliable serum index of demyelination in multiple sclerosis
Authors: Lubetzki C. , PharmD Y. Thuillier , PharmD A. Galli , Lyon‐Caen O. , Lhermitte F. , Zalc B.
Published: January 2005

Eight patients with multiple sclerosis were followed for several months to determine if serum levels of galactosylceramide, a major lipid component of myelin, correlate with the clinical evolution of the disease. In the patients with the chronic progressive form of multiple sclerosis, galactosycleramide remained undetectable. In the patients with relapsing‐remitting multiple sclerosis, there was a good correlation between the elevation of serum galactosylcermide levels and clinical relapses. This serum assay should prove of value in the follow‐up of patients with multiple sclerosis.
Midbrain dopaminergic cell loss in parkinson's disease: Computer visualization
Authors: German Dwight C. , Manaye Kebreten , Smith Wade K. , Woodward Donald J. , Saper Clifford B.
Published: January 2005

Computer visualization techniques were used to map the distribution of dopaminergic neurons within midbrain tissue sections from 5 parkinsonian patients and 3 age‐matched control subjects. The Parkinsonian brains had over 50% fewer dopaminergic neurons within the midbrain than age‐matched normal brains. The cell loss occurred within the combined substantia nigra (dopaminergic nucleus A9) and retrorubral (dopaminergic nucleus A8) areas (> 61%) and the ventral tegmental area (dopaminergic nucleus A10) (> 42%). The cell loss was greatest within the ventral portion of the substantia nigra zona compacta. The specific pattern of cell loss is very similar to the pattern of cells that project to the striatum (as opposed to cortical and limbic sites) in animal neuroanatomical tracing experiments. These data suggest that Parkinson's disease preferentially destroys midbrain dopaminergic neurons in nuclei A8, A9, and A10, which project to the striatum.
Low prevalence of neurological and neuropsychological abnormalities in otherwise healthy HIV‐1–infected individuals: Results from the multicenter AIDS cohort study
Authors: McArthur Justin C. , Cohen Bruce A. , Selnes Ola A. , Kumar Ashok J. , Cooper Kay , McArthur Julie H. , Soucy Gerry , Cornblath David R. , Chmiel Joan S. , Wang Mei‐Cheng , Starkey Danna L. , Ginzburg Harold , Ostrow David G. , Johnson Richard T. , Phair John P. , Polk B. Frank
Published: January 2005

Accurate description of the prevalence of neurological impairment in healthy individuals who are infected with human immunodeficiency virus type 1 (HIV‐1) has relevance for public health policy, for employment issues, and for planning future health needs. Within the Multicenter AIDS Cohort Study, we determined the cross‐sectional prevalence of neurological abnormalities in 270 HIV‐1 seropositive homosexual and bisexual men in Centers for Disease Control Groups II and III, using a control group of 193 HIV‐1 seronegative homosexual men. Utilizing a neurological and neuropsychological screening battery, we found no differences in the prevalence of neuropsychiatric symptoms or in neuropsychological performance. One hundred nineteen subjects with abnormalities on screening tests completed additional neuropsychological testing and had neurological examinations. The majority had normal results and the frequency of neurological abnormalities and impaired neuropsychological performance was not significantly increased among HIV‐1 seropositive subjects. Most of the abnormalities could be attributed to causes other than HIV‐1. One subject had mild HIV‐1–related dementia, yielding a prevalence of 3.7:1,000 (95% confidence interval: 0.19–23.7:1,000). Magnetic resonance imaging demonstrated sulcal prominence and focal areas of high signal intensity in white matter in 63% of HIV‐1 seropositive subjects and 48% of uninfected control subjects. Abnormalities in cerebrospinal fluid were noted in 23 (85%) of 27 HIV‐1–infected individuals. Our studies indicate that the prevalence of dementia and other HIV‐1–related neurological disorders is very low among healthy HIV‐1 seropositive homosexual men. The confounding effects of factors such a substance abuse or preexisting medical conditions must be considered in the neurological evaluation of such patients.
Vestibular responses in wernicke's encephalopathy
Authors: Furman Joseph M. R. , Becker James T.
Published: January 2005

Two patients with Wernicke's encephalopathy were evaluated with quantitative vestibulo‐ocular reflex and ocular motor testing. Vestibulo‐ocular reflex testing included caloric irrigation, earth vertical axis rotational sinusoids, and rotational impulses. Both patients demonstrated hypoactive vestibular responses to both caloric and rotational stimuli at the time of presentation. One patient had upbeating nystagmus that diminished with upgaze, downgaze, or convergence. Following treatment with thiamine, both patients' vestibular responses improved but remained abnormal, with a short vestibulo‐ocular reflex time constant and increased low‐frequency rotational phase lead. Impairment of the velocity storage element attributable to damage to the vestibular nucleus and nucleus prepositus hypoglossi may account for this permanent effect on the vestibulo‐ocular reflex.
AIDS‐related vacuolar myelopathy is not associated with coinfection by human T‐lymphotropic virus Type I
Authors: Brew Bruce J. , Hardy William , Zuckerman Evelyn , Chien Nancy , Paul Morris , Rosenblum Marc , Gadler Hakan , Vahlne Anders , Gold Jonathan , Armstrong Donald A. , Price Richard W.
Published: January 2005

Assessment of antibodies against human T‐lymphotropic virus type I (HTLV‐I) by enzyme‐linked immunoassay, immunofluorescence, and Western blot was undertaken in patients with pathologically or clinically diagnosed acquired immunodeficiency syndrome‐related vacuolar myelopathy to determine whether this retrovirus could be etiologically implicated in this disorder. No serological evidence for HTLV‐I was found in the patients with vacuolar myelopathy, though 1 patient with an atypical myelopathy did have antibodies against HTLV‐I.
A case of adult‐onset dementia with argyrophilic grains
Authors: Itagaki S. , McGeer P. L. , Akiyama H. , Beattie B. L. , Walker D. G. , Moore G. R. W. , McGeer E. G.
Published: January 2005

A case of progressive dementia in a 68‐year‐old woman was characterized by the postmortem finding of widespread argyrophilic grains in the cerebral cortex. The grains consisted of 10‐ to 13‐nm filaments in deposits ranging up to 9 μm in length and 3 μm in diameter. The grains stained positive with Alz‐50 monoclonal antibody. Cortical brain tissue levels were minimally elevated for acetylcholinesterase, moderately reduced for choline acetyltransferase, and sharply reduced for glutaminase. Although the case was clinically indistinguishable from Alzheimer's disease, plaque and tangle pathological findings were absent. We confirm cortical changes of the type described by Braak and Braak and provide additional data on subcortical changes in this case.
Abnormalities of the electron transport chain in idiopathic parkinson's disease
Authors: Parker William Davis , Boyson Sally J. , Parks Janice K.
Published: January 2005

Idiopathic Parkinson's disease may have a low‐level familial association but does not follow mendelian patterns of inheritance. Since inheritance of some components of the electron transport chain is nonmendelian and since inhibition of the electron transport chain with the toxin 1‐methy1‐4‐phenyl‐1,2,3,6‐tetrahydropyridine models Parkinson's disease in humans and animals, we evaluated catalytic activities of the electron transport chain in platelet mitochondria purified from patients with idiopathic Parkinson's disease. All 10 patients studied had significant reductions of complex I (NADH:ubiquinone oxidoreductase) activity. Succinate:cytochrome c oxidoreductase activity was less strikingly reduced. We hypothesize that the complex I abnormality may have an etiological role in the pathogenesis of Parkinson's disease and that this defect may be derived via the mitochondrial genome.
Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32–34
Authors: Kramer Patricia L. , De Leon Deborah , Ozelius Laurie , Risch Neil , Bressman Susan B. , Brin Mitchell F. , Schuback Deborah E. , Burke Robert E. , Kwiatkowski David J. , Shale Heidi , Gusella James F. , Breakefield Xandra O. , Fahn Stanley
Published: January 2005

Idiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non‐Jewish kindred was located on chromosome 9q32–34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32–34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine‐beta‐hydroxylase. The same gene may be responsible for ITD both in the non‐Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups.
Increased thymocyte differentiation in myasthenia gravis: A dual‐color immunofluorescence phenotypic analysis
Authors: Durelli L. , Massazza U. , Poccardi G. , Ferrio M. F. , Cavallo R. , Maggi G. , Casadio C. , Di Summa M. , Bergamini L.
Published: January 2005

Thymocytes express multiple, different surface antigens according to their stage of maturation. Surface differentiation antigens have been studied with the technique of simultaneous dual‐color, direct immunofluorescence in the thymuses of 20 patients with myasthenia gravis (MG) and 10 control subjects with cardiac diseases. Fluorescein isothiocyanate‐conjugated and phycoerythrin‐conjugated monoclonal antibodies were used to stain thymic cell suspensions. A significant decrease in the percentage of immature and common thymocyte phenotypes (CD1+,3+ and CD4+,8+) and significant increase in the percentage of mature thymocyte phenotypes (CD1‐,3+; CD4+,8‐; and CD4‐,8+) and of B cells (CD20+) were found in MG thymuses compared with controls. These data, indicating an increased availability of mature, fully immunocompetent T and B cells, indirectly suggest the occurrence of an active immune response in MG thymus.
Neural transplantation using temperaturesensitive immortalized neural cells: A preliminary report
Authors: Bredesen Dale E. , Hisanaga Kinya , Sharsp Frank R.
Published: January 2005

Current approaches to neural transplantation–adrenal medullary and fetal brain–suffer from limitations in tissue availability, cellular uniformity, and general applicability. The system described here uses temperature‐sensitive immortalized clonal neural cells to address these limitations. Cerebellar cells, immortalized with a temperature‐sensitive tumor virus, are transformed at 34°C, but differentiate at 38°C. The cells were genetically engineered to express beta‐galactosidase, providing a tag to study their fate in the host. The cells were then successfully transplanted to the cerebellum of adult rats.
The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system
Authors: Hartung Hans‐Peter , Schäfer Bärbel , Van Der Meide Peter H. , Fierz Walter , Heininger Kurt , Toyka Klaus V.
Published: January 2005

The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon‐gamma markedly augmented both myelin‐induced and T‐cell line‐mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon‐gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon‐gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.
The distribution of chromogranin A—like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy‐induced neuronal damage
Authors: Munoz David G.
Published: January 2005

The distribution of chromogranin A‐like immunoreactivity in the hippocampus of adult humans who were free of neurological disease was examined by immunohistochemical methods. Immunoreactivity was restricted to the cytoplasm of certain neuronal populations, most notably the mossy fibers of dentate granule cells (and a subset of their perikarya), and the perikarya of pyramidal cells of the cornu Ammonis 2 (CA2) sector. Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short‐axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus. Pyramidal neurons in the CA1 and CA3 sectors were not immunoreactive. The two prominently immunoreactive neuronal populations, CA2 pyramids and dentate granule cells, are those spared in human and experimental epileptic brain damage, whereas CA1 and CA3 pyramids, lacking chromogranin, are characteristically destroyed in this condition. The known activities of chromogranin in the periphery as a calcium‐binding protein and as a precursor of active peptides (autocrine inhibitory modulators) suggest that its distribution in the hippocampus may help to explain the observed pattern of resistance to epileptic brain damage.
Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome
Authors: Griffin J. W. , Cornblath D. R. , Alexander E. , Campbell J. , Low P. A. , Bird S. , Feldman E. L.
Published: January 2005

Thirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjögren's syndrome. In 11 Sjögren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less serverely affected. Most had evidence of autonomic insufficiency. In some this was servere, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T‐cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjögren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss.
Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies
Authors: Pestronk A. , Chaudhry V. , Feldman E. L. , Griffin J. W. , Cornblath D. R. , Denys E. H. , Glasberg M. , Kuncl R. W. , Olney R. K. , Yee W. C.
Published: January 2005

We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high‐titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme‐linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high‐titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84 ) high titers of anti‐GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti‐GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo GM1 that do not cross‐react with GM1 ganglioside.
Eyelid twitching seizures and generalized tonic‐clonic convulsions: A syndrome of idiopathic generalized epilepsy
Authors: Miller John W. , Ferrendelli James A.
Published: January 2005

This is a report of two neurologically normal patients who had primary generalized seizures consisting of irregular fluttering or twitching movements of the eyelids accompanied by generalized, rhythmic 9‐ to 15‐Hz electroencephalographic discharges as well as infrequent generalized tonic‐clonic seizures. This is a syndrome of idiopathic generalized epilepsy that responds to treatment with valproic acid.