bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance image–based hippocampal volumentry: Correlation with outcome after temporal lobectomy
Authors: Jack Clifford R. , Sharbrough Frank W. , Cascino Gregory D. , Hirschorn Kathryn A. , O'Brien Peter C. , Marsh W. Richard
Published: January 2005

We developed a magnetic resonance imaging (MRI)–based technique for measuring the volume of the hippocampal formation. In this study, the relationship between volumes of the hippocampal formation and outcome (i.e., postoperative seizure control) after anterior temporal lobectomy for intractable epilepsy was analyzed in 50 consecutive patients in whom the surgical specimen did not contain an epileptogenic mass lesion. Outcome was classified as either satisfactory or unsatisfactory. A significant relationship was found between outcome and volume of the operated of hippocampal formation (p = 0.012), as well as a derived volumetric measure (nonoperated minus operated volume of the hippocampal formation) (p = 0.004). The association between outcome and nonoperated volume was borderline (p = 0.057). Thirty‐four (97%) of 35 patients in whom the volumetric study and electroencephalography (EEG) concordantly lateralized the seizure disorder had satisfactory postoperative seizure control. Conversely, only 7 (42%) of 12 patients in whom the volume study was nonlateralizing and 1 (33%) of 3 in whom the EEG and volume study were discordant had a satisfactory outcome. We regard our MRI‐based study of hippocampal formation volume as a noninvasive surrogate for the identification of moderate or severe mesial temporal sclerosis. The technique is a useful adjunct in a multidisciplinary, preoperative epilepsy evaluation when T2‐weighted MRIs do not reveal an epileptogenic mass lesion. The reasons for the usefulness of this imaging technique are: (1) It is an independent source of information on seizure lateralization, (2) it will provide information as to expected postoperative outcome, and (3) it may aid in appropriately selecting patients for invasive preoperative monitoring studies.
Creutzfeldt‐Jakob disease cosegregates with the codon 178AsnPRNP mutation in families of European origin
Authors: Goldfarb Lev G. , Brown Paul , Haltia Matti , Cathala Françoise , McCombie W. Richard , Kovanen Jussi , Červen̆áková Larisa , Goldin Lynn , Nieto Ana , Godec Mark S. , Asher David M. , Gajdusek D. Carleton
Published: January 2005

We recently discovered an amino acid–altering heterozygous mutation in codon 178 of the PRNP amyloid precursor gene in patients with familial Creutzfeldt‐Jakob disease. This mutation is now shown to be associated with the occurence of disease in 7 unrelated families of Western European origin, among which a total of 65 members are known to have died from Creutzfeldt‐Jakob disease. The mutation was detected in each of 17 tested patients, including at least 1 affected member of each family, and in 16 of 36 of their first‐degree relatives, but not in affected families with other mutations, patietns with the nonfamilial form of the disease, or 83 healthy control individuals. Linkage analysis in two informative families yielded a lod score of 5.30, which, because no recombinants were found, strongly suggests that codon 178Asn is the actual disease mutation.
Vascular differentiation and glucose transporter expression in rat gliomas: Effects of steroids
Authors: Guerin Christopher , Wolff Johannes E. A. , Laterra John , Drewes Lester R. , Brem Henry , Goldstein Gary W.
Published: January 2005

The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone‐induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 ± 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 ± 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 ± 10.5%), lower vascular density (102 ± 64 vessels/mm2), and smaller tumor size (control cross‐sectional area, 17.0 ± 3.4 mm2; treated, 4.6 ± 1.0 mm2). Essentially all vessels became GLUT1‐positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive.
Autoimmune inflammation of astrocyte transplants
Authors: Lublin Fred D. , Marini Joseph C. , Perreault Marielle , Olender Christina , D'Imperio Concetta , Joseph Jeymohan , Korngold Robert , Knobler Robert L.
Published: January 2005

Astrocytes have been shown to be capable of serving as antigen‐presenting cells and as targets for encephalitogenic cytotoxic T lymphocytes. The role of astrocytes in central nervous system (CNS) autoimmune inflammation is unclear. To study this further, we transplanted astrocyte aggregates into the anterior eye chamber of the mouse. The astrocytic nature of these transplants was confirmed by immunohistochemical detection of glial fibrillary acidic protein and the inability to detect oligodendrocyte or microglial markers. When mice bearing transplants were induced to develop experimental allergic encephalomyelitis by either passive or active protocols, the astrocyte transplants developed a perivascular inflammatory response similar to that seen in the host CNS during the course of the encephalomyelitis. The data suggest that astrocytes could serve as targets for the autoimmune attack of experimental allergic encephalomyelitis and support the possibility that the pathogenesis of this disease may involve an autoimmune reaction against a site other than the myelin sheath.
Neurology research: A journal survey, 1980–1990
Authors: Jamieson Patrick W.
Published: January 2005

There have been major changes in neurology research during the past decade, but no systematic examination of the content, methods, funding, and research personnel. All scientific articles in the journals Annals of Neurology, Archives of Neurology, and Neurology were categorized by article type, number of authors, highest degree of first author, institution, disease area, reseach field, and source of support for the years 1980 and 1990. Original articles grew by 54% over the decade. The average number of authors increased by 1.3 to 5 (p > 0.0001). Groups of MDs and PhDs wrote 39% of articles in 1990 (24% in 1980). Contributions with a diagnostic or therapeutic focus rose from 7 to 14%, whereas there was a pronounced drop in case reports from nearly 40% to just under 20%. Articles on movement disorders and neurodegenerative diseases increased more than 100% and now together comprise more than 25% of original articles. Molecular biology increased by 1,600%, and there was significant growth in epidemiology, neuroimaging, neurochemistry, and neuropsychology. The top 20 publishing institutions accounted for 40% of all original articles and 60% of US original articles. Foreign contributions doubled over the decade. The National Institutes of Health funded 46% of US articles in 1990 (35.5% in 1980). More than 80% of articles in 1990 on neurodegenerative disease were supported by the National Institutes of Health. The complexity of neurological research has driven greater collaboration between basic and clinical scientists. New areas of clinical and basic knowledge are rapidly emerging in neurology.
Plasma exchange in Guillain‐Barré syndrome: One‐year follow‐up
Authors:   French Cooperative Group on Plasma Exchange in Guillain‐Barré Syndrome
Published: January 2005

We report the one‐year assessment of plasma exchange (PE) versus control in Guillain‐Barré syndrome (GBS), based on a randomized multicenter clinical trial of 220 patients with GBS. Treated patients received four PEs, with either albumin or fresh frozen plasma (FFP) as replacement fluid. This study completes the short‐term analysis previously published (Ann Neurol 1987;22:753–761).

Long‐term benefit from PE was observed, as demonstrated by full muscular strength recovery at one year: 71% in the PE group versus 52% in the control group (p = 0.007), confirmed after adjustment for four prognostic factors. FFP showed no additional benefit compared with albumin (77% full recovery in the FFP group versus 65% in the albumin group; p = 0.22). PE did not affect the incidence of severe motor disability (11% in both groups).
Hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke: Influence on the rate of subsequent stroke
Authors: van Swieten J. C. , Kappelle L. J. , Algra A. , van Latum J. C. , Koudstaal P. J. , van Gijn J.
Published: January 2005

In a prospective study of 3,017 patients with transient ischemic attack or minor ischemic stroke from the Dutch Transient Ischemic Attack Trial, the presence or absence of diffuse hypodensity of the white matter on a baseline computed tomography (CT) scan of the brain was related to the occurrence of subsequent stroke. On entry, 337 patients were judged to have diffuse hypodensity of the white matter on CT; they were older (71.4 ± 7.4 years versus 64.4 ± 9.9 years), more often had hypertension (50% versus 41%), and more often had lacunar infarcts on CT scan (40% versus 26%) than did patients with normal white matter. Strokes, fatal or nonfatal, occurred in 51 (15%) of the patients with diffuse hypodensity of the cerebral white matter, compared to 217 (8%) in the group with normal white matter (crude hazard ratio, 2.0; 95% confidence interval, 1.4–2.7). After adjustment for age and other relevant entry variables, the hazard ratio was 1.6 (95% confidence interval, 1.2–2.2). In patients younger than 70 years the crude hazard ratio was 2.7 (95% confidence interval, 1.7–4.2). The distribution between the main subtypes of stroke was similar for patients with and those without diffuse hypodensity of the cerebral white matter: Intracerebral hemorrhage occurred in 6 and 9%, cortical infarction in 47 and 45%, and lacunar infarction in 34 and 29%, respectively. We conclude that hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke is associated with an extra risk of future stroke, from large as well as from small vessels, and particularly in patients under 70 years old; this increase of risk is independent of other risk factors for stroke.
A novel neuronal messenger molecule in brain: The free radical, nitric oxide
Authors: Dawson Ted M. , Dawson Valina L. , Snyder Solomon H.
Published: January 2005

Understanding of the organization and function of a newly identified neuronal messenger molecule, nitric oxide, has progressed rapidly. Nitric oxide synthase has been purified and molecularly cloned from brain. Its localization is exclusively neuronal and endothelial. The catalytic activity of nitric oxide synthase accounts for the NADPH diaphorase staining of neurons that are uniquely resistant ot toxic insults and neurodegenerative disorders. Nitric oxide has diverse functions. In platelets it inhibits their aggregation, in macrophages it mediates cytotoxicity, and in blood vessels it acts as a vasodilator. In the nervous system nitric oxide may be the retrograde transmitter in long‐term potentiation. It is the “neurotransmitter” of cerebral vasodilator nerves and the inhibitory “neurotransmitter” of the motor neurons of the intestines. Nitric oxide in situations of excessive production may function as neurotoxin, suggesting a role for nitric oxide in neurodegenerative disorders.
Motor inhibition and excitation are independent effects of magnetic cortical stimulation
Authors: Triggs William J. , Macdonell Richard A. L. , Cros Didier , Chiappa Keith H. , Shahani Bhagwan T. , Day Bruce J.
Published: January 2005

We administered magnetic cortical stimulation (MCS) during voluntary contraction of intrinsic hand muscles to 8 patients with motor neuron disease (MND), 5 patients with pure lower motor neuron syndromes (LMN), a patient with severe subacute sensory neuropathy (SSN), and 10 healthy volunteers. Patients with MND had clinical evidence of upper MND and elevated thresholds for (3 patients) or absence of (5 patients) motor evoked potentials (MEPs). MCS during sustained contraction inhibited electromyographic activity in 6 of 8 patients with MND, without preceding MEPs. MCS had no effect on the electromyogram (EMG) of the other 2 patients with MND. In normal subjects and patients with LMN inhibition of EMG was never seen without a preceding MEP, regardless of stimulus intensity. In the patient with SSN, MCS elicited normal MEPs and inhibited the EMG in a pattern similar to normal subjects, whereas supramaximal electrical stimulation of median and ulnar nerves failed to inhibit the EMG despite normal M and F responses. Our findings indicate that the inhibitory effects of MCS on EMG are not dependent solely on changes in afferent feedback caused by the muscle twitch produced by the MEP, or on Renshaw cell inhibition. We suggest that some of the inhibitory and excitatory effects of MCS on the motor system are mediated by distinct cortical elements, which may have different susceptibilities to pathophysiological processes in MND.
Felbamate monotherapy: Controlled trial in patients with partial onset seizures
Authors: Sachdeo Rajesh , Kramer Lynn D. , Rosenberg Alberto , Sachdeo Satinder
Published: January 2005

Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single‐center, randomized, double‐blind, parallel‐group trial. During the 56‐day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one‐third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two‐fold increase in monthly seizure frequency, two‐fold increase in highest 2‐day seizure frequency, single generalized tonic‐clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p < 0.001, chi‐square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.
Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease
Authors: Kalaria Rajesh N. , Harik Sami I.
Published: January 2005

L‐Carnitine and acetyl‐L‐carnitine facilitate mitochondrial β‐oxidation of fatty acids. In the brain, they may also have a role in acetylcholine synthesis. Carnitine acetyltransferase catalyzes the interchange between L‐carnitine and acetyl‐L‐carnitine. Recently, acetyl‐L‐carnitine was reported to have a beneficial effect in patients with Alzheimer's disease. We therefore assessed carnitine acetyltransferease activity in selected brain regions and in isolated cerebral microvessels obtained at autopsy from patients with Alzheimer's disease and from age‐matched control subjects. We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels. These findings document another neurochemical abnormality in patients with Alzheimer's disease and provide a rationale for the use of acetyl‐L‐carnitine in the treatment of patients with Alzheimer's disease.
Electron transfer complex I defect in idiopathic dystonia
Authors: Benecke Reiner , Strümper Petra , Weiss Hanns
Published: January 2005

It has been suggested that dystonia is caused by an autosomal gene with reduced penetrance and a consequent biochemical abnormality affecting cell activity within the basal ganglia. No consistent biochemical disturbance has been identified. In the present study, activities of the mitochondrial electron transfer complexes were measured in platelets of 31 patients with idiopathic dystonia. Enzyme assays of these patients were compared to measurements in 28 control subjects. A significant decrease of complex I activity was observed in the majority of the patients, whereas the activities of other electron transfer complexes were normal. The severity of the complex I defect was more pronounced in patients with the segmental or generalized form than in those with focal dystonia. Complex I activity was not age dependent in the patients or control subjects. Although the electron pathway in complex I is disturbed in patients with idiopathic dystonia, complex I protein content seems to be normal. Whether abnormalities of complex I activity play a role in the pathogenesis of idiopathic dystonia remains to be determined.
The antiparkinson efficacy of deprenyl derives from transient improvement that is likely to be symptomatic
Authors: Schulzer M. , Mak E. , Calne D. B.
Published: January 2005

We undertook an analysis of the hazard functions derived from results published by the Parkinson Study Group following their investigation of deprenyl. Our findings indicate that the action of deprenyl is transient rather than sustained. We also infer that this effect may be mediated through alleviation of symptoms rather than by neuroprotection.
Cytochrome c oxidase activity in single muscle fibers: Assay techniques and diagnostic applications
Authors: Johnson Margaret A. , Bindoff Laurence A. , Turnbull Douglass M.
Published: January 2005

Microphotometric enzyme assay was used to study cytochrome c oxidase activity in single human skeletal muscle fibers. The assay techniques combine the precise localization of enzyme activity provided by histochemical methodology with the precise quantitation of a sensitive assay system. Abnormalities of cytochrome c oxidase were investigated using microphotometric enzyme assay in 12 patients with Kearns‐Sayre syndrome, chronic progressive external ophthalmoplegia, or Leigh's syndrome. Control values were obtained using muscle biopsy specimens from 20 juvenile and 18 adult subjects with no evidence of neuromuscular disease. In the patients with Leigh's syndrome due to cytochrome c oxidase deficiency, the abnormality was found to be expressed uniformly throughout the muscle fiber population. In contrast, patients with Kearns‐Sayre syndrome or chronic progressive external ophthalmoplegia showed abnormal heterogeneity of cytochrome c oxidase activity. In many cases, extreme degrees of variability were seen, with fibers containing high activity adjacent to fibers with no detectable activity. Mitochondrial DNA analysis showed that most of the patients with Kearns‐Sayre syndrome and chronic progressive external ophthalmoplegia had major rearrangements of mitochondrial DNA. It was concluded that the extreme variability of cytochrome c oxidase activity detected using microphotometric enzyme assay was an indicator of a probable abnormality of mitochondrial DNA. Conversely, cytochrome c oxidase defects in muscle which show a homogeneous distribution are more likely to be associated with defects of the nuclear genome.
Rapidly progressive aphasic dementia and motor neuron disease
Authors: Caselli Richard J. , Windebank Anthony J. , Petersen Ronald C. , Komori Takashi , Parisi Joseph E. , Okazaki Haruo , Kokmen Emre , Iverson Rita , Dinapoli Robert P. , Graff‐Radford Neill R. , Stein Steven D.
Published: January 2005

Articulatory and language impairment heralded rapidly progressive motor neuron disease in 7 patients aged 54 to 77 years. One patient had a family history of a similar disorder. Severe nonfluent aphasia developed in all 7 patients and 4 were anarthric within a year. Other cognitive domains were impaired, yet 2 patients lived alone until 1 month before their deaths. Four died within 2 years. Abnormalities were found on electromyography, computed tomography, magnetic resonance imaging, single‐photon emission computed tomography, and electroencephalography. Neuropathological examination in 3 patients showed bilateral hemispheric atrophy with neuronal loss and gliosis predominantly of superficial cortical layers. Pigmented and hypoglossal nuclei were relatively preserved. At all spinal levels there was degeneration of corticospinal tracts and loss of anterior horn cells with gliosis. Rapidly progressive aphasic dementia and motor neuron disease are a distinctive clinical entity whose nosology is poorly understood.
Human class I major histocompatibility complex transgene prevents virus‐induced demyelination in susceptible mutant B 10.d2dml mice
Authors: Rodriguez M. , Pedrinaci S. , David C. S.
Published: January 2005

Theiler's murine encephalomyelitis virus (TMEV) induces immune‐mediated demyelination in susceptible strains of mice, providing an excellent model for multiple sclerosis. Class I genes within the major histocompatibility complex locus (H‐2D region)play a major role in determining whether strains of mice develop chronic in determining whether strains of mice develop chronic demyelination and TMEV persistence. B 10.D2dml mice with deletion in the 3′ end of Dd and the 5′ end of Ld genes develop the most prominent demyelination in comparison with resistant B10. D2 mice normal complementation of H‐2D region genes. We tested whether expression of a class I human transgene (HLA‐B27) would modulate virus‐induced demyelination in mutant B10.D2dml mice. Transgenic B10.D2dml (HLA‐B27+) mice infected with virus showed dramatic decrease in the extent of demyelination (p < 0.0001) and virus antigen expression in spinal cord compared with littermate controls without the human class I transgene. These experiments demonstrate that transgenic expression of a human class I major histocompatibility complex locus molecule can prevent demyelination induced by a virus in mutant mice.
Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/ magnetic resonance scan
Authors: DeAngelis Lisa M.
Published: January 2005

Cerebral lymphoma is usually indentified on computered tomographic/magnetic resonance scan as a homogeneously contrast‐enhancing periventricular mass lession. We present 10 patients with cerebrllymphoma who had nonenhancing tumor on computed tomographic (2 patients) or magnetic resonance scan (8 patients) either at the time of diagnosis or recurrence. The absence of enhancement caused diagnostic delay in all patients and suggests that tumor resides behind an intact blood brain barrier, raising important therapeutic implications in the design of chemotherapeutic regimens.
A controlled trial of lazabemide (RO19–6327) in untreated Parkinson's disease
Authors:   Parkinson Study Group, Kieburtz Karl
Published: January 2005

The monoamine oxidase type B inhibitor deprenyl (selegiline) has been demonstrated to delay the emergence of disability in early untreated Parkinson's disease. Lazabemide (RO19–6327) is a short‐acting, reversible, highly selective inhibitor of monoamine oxidase type B which, unlike deprenyl, is not metabolized to active compounds. We conducted a randomized, double‐blinded clinical trial to assess the short‐term tolerability of lazabemide in subjects who had early, untreated Parkinson's disease. Two hundred and one patients were enrolled at 14 centers and randomized to receive 100 mg/day, 200 mg/day, or 400 mg/day of lazabemide or matching placebo. Subjects were followed for 8 weeks including a randomized, double‐blinded withdrawal of lazabemide for 2 or 4 weeks. The primary measure of tolerability was the proportion of treated subjects who were able to complete the study on their originally assigned treatment. Clinical features were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). Lazabemide treatment was as well tolerated as placebo and was not attended by serious adverse experiences. A significant improvement in the activities of daily living component of the rating scale was found after 4 weeks of lazabemide treatment, although other subscale scores did not change significantly. The overall safety and benefits of lazabemide observed in this short‐term study justify further long‐term investigations to determine if this monoamine oxidase type B inhibitor can slow the clinical progression of Parkinson's disease.
Callosal apraxia without agraphia
Authors: Kazui Seiji , Sawada Tohru
Published: January 2005

We describe a patient with left unilateral ideomotor apraxia without left‐sided agraphia caused by a callosal lesion that was demonstrated by magnetic resonance imaging. The clinical features, together with data in the literature, suggest that the callosal fibers for writing are concentrated in the posterior corpus callosum, while those for praxis cross in the more rostral part of the posterior half of the callosum.
Delayed administration of memantine prevents N‐methyl‐D‐aspartate receptor‐mediated neurotoxicity
Authors: Pellegrini James W. , Lipton Stuart A.
Published: January 2005

Increasing evidence supports the hypothesis that escalating levels of excitatory amino acids (EAAs) are responsible for neuronal cell death in a variety of acute neurological conditions including hypoxia/ischemia, trauma, seizures, and hypoglycemia. EAAs may also contribute to several chronic neurodegenerative diseases including Huntington's disease, parkinsonism, and acquired immunodeficiency syndrome dementia. A predominant form of neurotoxicity appears to be mediated by excessive activation of the N‐methyl‐D‐aspartate subtype of glutamate receptor. This laboratory recently reported that memantine, an antiparkinsonian drug, is a potent N‐methyl‐D‐aspartate antagonist capable of preventing the death of central neurons both in vitro and in vivo when given coincident to an EAA insult. In the present study, we found that 12 μM memantine prevented the death of neonatal rat retinal ganglion cells in primary culture when administered up to 4 hours after the initiation of N‐methyl‐D‐aspartate receptor‐mediated neurotoxicity.
Nonepileptic seizures during apparent sleep
Authors: Thacker Kimberley , Devinsky Orrin , Perrine Kenneth , Alper Kenneth , Luciano Daniel
Published: January 2005

We report 12 patients with nonepileptic seizures(NESs) documented with video‐electroencephalographic monitoring during apparent sleep. There were 7 females and 5 males, ages 11 to 67 years(mean, 33 yr). In all patients there was a well‐organized posterior α rhythm present immediately before onset of clinical changes despite the appearance of sleep. Patients later “confirmed” that these attacks occured during sleep. Features of these episodes were typical of NESs and none were associated with ictal or postictal electroencephalographic changes other than muscle and movement artifact. Provocative testing with suggestion confirmed the nonepileptic nature of these episodes in 9 patients. Three patients had epileptiform discharges during prolonged interictal recordings and 1 had a documented complex partial seizure. Our findings indicate that reports of seizures during sleep are not uncommon among patients with NESs.
Spinal fluid lymphocytes from a subgroup of multiple sclerosis patients respond to mycobacterial antigens
Authors: Birnbaum Gary , Kotilinek Linda , Albrecht Lisa
Published: January 2005

Immune responses to heat shock or stress proteins are observed in several chronic autoimmune diseases. Such proteins are major antigens of many bacteria, especially mycobacteria. To determine whether immune responses to stress proteins occur in chronic inflammatory diseases of the central nervous system such as multiple sclerosis (MS) we measured proliferative responses of lymphocytes from spinal fluids and bloods of patients with MS and other neurological diseases to a sonicate of M. tuberculosis, an acetone extract of M. tuberculosis, a recombinant 65‐kd heat shock protein of M. leprae, and tetanus toxoid as a control recall antigen. Significantly increased spinal fluid lymphocyte responses to mycobacterial sonicate, relative to responses from paired peripheral blood lymphocytes, were present in 14 of 20 specimens from patients with MS (p < 0.025) and 2 of 9 specimens from patients with other neurological diseases. Spinal fluid lymphocytes also responded to tetanus toxoid, but differences between blood and spinal fluid were not statistically significant. Lymphocytes from 1 patient with MS responded only to M. leprae. There were no proliferative responses to the M. tuberculosis acetone extract. When patients with MS were classified according to duration of disease (<2‐ or >2‐yr duration) 9 of 10 patients with recent onset had cerebrospinal fluid cells that responded to M. tuberculosis compared with 5 of 10 with longer duration symptoms (p < 0.012). Our data suggest a selective recruitment and/or expansion of mycobacterial reactive cells to the central nervous system of a subpopulation of patients with MS. Immune responses to antigens present in mycobacteria, possibly stress proteins, may be important in perpetuating and amplifying chronic inflammatory diseases of the central nervous system such as MS.
The human–severe combined immunodeficiency myasthenic mouse model: A new approach for the study of myasthenia gravis
Authors: Martino Gianvito , DuPont Bonita L. , Wollmann Robert L. , Bongioanni Paolo , Anastasi John , Quintans Josè , Arnason Barry G. W. , Grimaldi Luigi M. E.
Published: January 2005

We have established a new chimeric human‐mouse model of myasthenia gravis in severe combined immunodeficiency mice, using human peripheral blood lymphocytes that survive in the mouse and produce specific antibodies that mediate pathological changes typical of human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti–acetylcholine receptor (AChR) antibody–positive and –negative patients with myasthenia gravis showed circulating anti–acetylcholine receptor antibodies, deposition of human IgG at muscle end‐plates, and simplification of the postsynaptic membrane, findings characteristic of human myasthenia gravis. Mice given human peripheral blood lymphocytes from healthy donors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells to reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune regulation in autoimmunity.
Dopa resistance in multiple‐system atrophy: Loss of postsynaptic D2 receptors
Authors: Churchyard A. , Donnan G. A. , Hughes A. , Howells D. W. , Woodhouse D. , Wong J. Y. F. , Kalnins R. M. , Mendelsohn F. A. O. , Paxinos G.
Published: January 2005

Postmortem autoradiography was used to explor the mechanisms underlying L‐dopa resistance in 2 patients with multiple‐system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H‐SCH 23390, and 123I‐sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple‐system atrophy, resistance to L‐dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.
Diffuse noxious inhibitory controls in humans: A neurophysiological investigation of a patient with a form of Brown‐Séquard syndrome
Authors: Bouhassira Didier , Le Bars Daniel , Bolgert Francis , Laplane Dominique , Willer Jean‐Claude
Published: January 2005

In normal subjects, the application of heterotopic painful stimuli induces simultaneous and parallel decrease in the sensation of pain and of the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is absent in tetraplegic patients with clinically complete spinal cord transections and can be triggered only from the analgesic hand in patients with Wallenberg's syndrome. These findings suggest that the inhibitory phenomena observed in normal subjects are likely to be examples of diffuse noxious inhibitory controls (DNICs), being sustained by a loop involving supraspinal structures, the ascending part of which is localized in the spinoreticular tract. We now report an exceptional case of a patient with Brown‐Séquard syndrome due to a 4‐year‐old spinal cord lesion (left side, T‐6 level) produced by a knife‐wound in the back. Nociceptive flexion (RIII) reflexes elicited by stimulation of cutaneous afferents in the ulnar and sural nerves were studied in the upper and lower limbs by recording from the biceps brachialis and biceps femoris muscles, respectively. For each limb, the RIII reflex threshold was determined. The reflex was then elicited regularly by stimuli of 1.2 times threshold before, during, and after periods of nociceptive electrical conditioning stimulation (15 mA; 4Hz; 1 min) applied successively to the other three limbs. Inhibitions of around 90% followed by after effects (2–3 min) were observed in all situations except that (1) no inhibition could be obtained when the conditioning stimuli were applied to the lower right limb (contralateral to the spinal lesion) and (2) the RIII reflex in the lower left limb was completely insensitive to any of the conditioning stimuli. These results suggest that in humans (1) the ascending part of the loop subserving DNICs is completely crossed at the spinal level and (2) the descending part is confined to the white matter ipsilateral to the limb being tested.
Long‐term follow‐up of 121 patients with benign fasciculations
Authors: Blexrud Marceil D. , Windebank Anthony J. , Daube Jasper R.
Published: January 2005

Using the case records of Mayo Clinic patients, 121 patients with a diagnosis of benign fasciculations were identified. All had a normal neurological examination and normal electrophysiological studies, except for fasciculation potentials. Interviews by telephone were conducted 2 to 32 years after diagnosis. None of the patients developed symptomatic motor neuron disease. Forty individuals were in health care careers. A subset of 19 patients described acute onset of fasciculations following a viral infection. Benign fasciculations are not a prelude to progressive motor neuron disease.
Quinolinic acid in children with congenital hyperammonemia
Authors: Batshaw Mark L. , Robinson Michael B. , Hyland Keith , Djali Sina , Heyes Melvyn P.
Published: January 2005

Levels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammonemia. Twofold to tenfold elevations of QUIN were found in 4 neonates in hyperammonemic coma (QUIN range, 250–990 nM; control mean, 110 ± 90 nM; p < 0.005). Similar elevations of neopterin were found (range, 24–75 nM; control mean, 9.0 ± 4.9 nM; p < 0.005). In addition, significant elevations of QUIN were found in 14 older children with congenital hyperammonemia (mean, 50 ± 20 vs 17 ± 6 nM; p < 0.05). Neopterin levels were not elevated in these children. The QUIN may originate from an increase in tryptophan transport across the blood‐brain barrier or from induction of indolamine‐2,3‐dioxygenase activity. These findings support a role for QUIN in the neuropathology of congenital hyperammonemia. They also suggest the potential utility of N‐methyl‐D‐aspartate receptor–‐blocking agents or inhibitors of QUIN synthesis in the treatment of hyperammonemic coma.
Herpes simplex type 2 in a patient with Mollaret's meningitis: Demonstration by polymerase chain reaction
Authors: Cohen Bruce A. , Rowley Anne H. , Long Christopher M.
Published: January 2005

We describe a patient with recurrent self‐limited aseptic meningitis meeting the criteria for Mollaret's syndrome, in whom extensive serological investigation and cerebrospinal fluid analysis failed to reveal a specific cause. Using polymerase chain reaction techniques to amplify herpes simplex viral DNA, we were able to identify the presence of herpes simplex virus type 2 in the cerebrospinal fluid. The duration of clinical illness may have been shortened by treatment with intravenous acyclovir. We suggest that herpes simplex virus may be a more common cause of aseptic meningitis than has been demonstrated by current commonly available serological and culture techniques.
Human β‐mannosidase deficiency associated with peripheral neuropathy
Authors: Levade T. , Graber D. , Flurin V. , Delisle M‐B. , Pieraggi M‐T. , Testut M‐F. , Carrière J‐P. , Salvayre R.
Published: January 2005

Human β‐mannosidosis is an inherited lysosomal storage disorder described in only seven families. We present a further case in a black African 14‐year‐old boy with severely deficient β‐mannosidase activity, bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The clinical and biochemical features of our patient are compared to those of previously reported patients.
Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation
Authors: Drachman Daniel B. , Chaudhry Vinay , Cornblath David , Kuncl Ralph W. , Pestronk Alan , Clawson Lora , Mellits E. David , Quaskey Shirley , Quinn Thomas , Calkins Allison , Order Stanley
Published: January 2005

Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double‐blind, randomized, placebo‐controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI‐treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI‐treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2‐year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.
Ciliary neurotrophic factor: Pharmacokinetics and acute‐phase response in rat
Authors: Dittrich Falk , Theonen Hans , Sendtner Michael
Published: January 2005

Ciliary neurotrophic factor (CNTF) supports the survival of motoneurons in vitro and in vivo. Recombinant CNTF is an investigational drug for the treatmentof amyotrophic lateral sclerosis. We determined the pharmacokinetics of radioiodinated CNTF after intravenous injection into rats. CNTF shows a biphasic clearance with an initial plasma half‐life of 2.9 minutes and is removed from the circulation by the liver. No accumulation of radioactivity was detectable in nerve tissue or skeletal muscle after intravenous injection of 0.1 μg and 0.5 μg of CNTF. Radioactive degradation products accumulate in the skin. Liver cells express specific binding proteins for CNTF, and the incorporation and degradation of intravenously injected CNTF by the liver may occur after association of CNTF with the soluble CNTF receptor α in the circulation. Probably as a consequence of its binding to hepatocytes, CNTF induces acute‐phase responses in liver. The short half‐life and the inflammatory side effect may limit the clinical usefulness of systematically administered CNTF in the treatment of human motoneuron disorders.
Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy
Authors: Garcia Paul A. , Laxer Kenneth D. , van der Grond Jeroen , Hugg James W. , Matson Gerald B. , Weiner Michael W.
Published: January 2005

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 ± 0.05 vs 7.00 ± 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 ± 6.0 vs 23.0 ± 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.
Neuronal migration disorders: Positron emission tomography correlations
Authors: Lee Namsoo , Radtke Rodney A. , Gray Linda , Burger Peter C. , Montine Thomas J. , DeLong G. Robert , Lewis Darrell V. , Oakes W. Jerry , Friedman Allan H. , Hoffman John M.
Published: January 2005

We analyzed the interictal [18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography (PET) findings of 17 epileptic patients with neuronal migration disorders (NMDs). Fifteen patients had abnormal PET findings, i.e., focal hypometabolism in 9 patients and displaced metabolic activity of normal gray matter in 6. All 15 patients had magnetic resonance imaging (MRI) abnormalities; however, PET abnormality assisted in the identification of NMDs on MRI in 3 patients. Two patients with negative MRI also had negative PET studies. PET hypometabolism appeared to correlate with severity of neuronal dysgenesis or temporal lobe involvement, or both. Displaced metabolic activity of gray matter is regarded as a unique interictal [18F]fluoro‐2‐deoxy‐D‐glucose–PET finding in NMD. This study demonstrates variable metabolic patterns in NMD and that PET may be a useful complement to MRI in the evaluation of NMD.
Intravascular malignant lymphomatosis: Amelioration of neurological symptoms with plasmapheresis
Authors: Harris Cheryl P. , Sigman June D. , Jaeckle Kurt A.
Published: January 2005

Intravascular malignant lymphomatosis is a rare disease that is uniformly fatal when disseminated. Chemotherapeutic and radiation therapy regimens have provided short‐term amelioration of symptoms but have not affected overall survival. We describe a patient with diffuse neurological symptoms who responded transiently but dramatically to plasmapheresis. This marked response warrants further evaluation of this therapy in intravascular malignant lymphomatosis.
FK506‐induced neurotoxicity in liver transplantation
Authors: Wijdicks Eelco F. M. , Wiesner Russell H. , Dahlke Linda J. , Krom Ruud A. F.
Published: January 2005

We report FK506‐induced neurotoxicity in 14 of 44 consecutive patients following orthoptic liver transplantation. In 10 of these 14 patients, postural hand tremors were found in the first weeks following surgery, transient apraxia of speech in 3, and generalized tonic‐clonic seizures were noted in 2 patients. Other manifestations included nightmares, agitation, and acute delirium. Reduction of the FK506 dose resulted in resolution of symptoms, but in 1 patient mild speech difficulties and in 3 patients a fine tremor remained. Blood and plasma levels of FK506 were similar in patients with and without neurotoxicity. FK506 neurotoxicity in patients with liver transplantation commonly results in transient neurological manifestations. The incidence of neurotoxicity in FK506 is dramatically reduced in maintenance doses of 0.075 mg/kg twice a day.
Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease
Authors: Simpson Ian A. , Chundu Koteswara R. , Davies‐Hill Theresa , Honer William G. , Davies Peter
Published: January 2005

Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.
Wearing‐off fluctuations in Parkinson's disease: Contribution of postsynaptic mechanisms
Authors: Bravi D. , Mouradian M. M. , Roberts J. W. , Davis T. L. , Sohn Y. H. , Chase T. N.
Published: January 2005

Wearing‐off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady‐state optimal‐dose infusion of apomorphine. Although the plasma half‐life of this dopamine receptor agonist remained constant, its mean efficacy half‐time declined from 66 minutes in early, levodopa‐naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing‐off fluctuations.