bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning of human anti‐GM1 antibodies from motor neuropathy patients
Authors: Willison Hugh J. , Paterson Gary , Kennedy Peter G. E. , Veitch Jean
Published: January 2005

Patients with multifocal motor neuropathy frequently have elevated titers of serum antibodies reactive with GM1 ganglioside. Although these antibodies may cause the syndrome, this has yet to be proven directly. As part of our studies on the nature and pathogenic potential of anti‐GM1 antibodies, we have cloned B cells from the peripheral blood of 3 patients with multifocal motor neuropathy and generated four stable heterohybridoma cell lines secreting human monoclonal IgM anti‐GM1 antibodies. In this report we describe the basic properties of these monoclonal antibodies in comparison with the patient's sera from which they were derived. The antibodies all differ in their pattern of reactivity with GM1 and other Gal(β1–3)GalNAc‐containing glycoconjugates. They have widely varying thermal ranges and their reactivities are strongly influenced by the presence of accessory lipids. Affinity purification of the patient's sera with GM1 led to the identification of previously unrecognized paraproteins that were resolvable above the background of polyclonal anti‐GM1 IgM. Our data demonstrate considerable heterogeneity in the immune response to GM1 both within individual sera and between different patients, which is likely to be of importance to their role in disease pathogenesis.
Benign infantile familial convulsions are not an allelic form of the benign familial neonatal convulsions gene
Authors: Malafosse A. , Beck C. , Bellet H. , Di Capua M. , Dulac O. , Echenne B. , Fusco L. , Lucchini P. , Ricci S. , Sebastianelli R. , Feingold J. , Baldy‐Moulinier M. , Vigevano F.
Published: January 2005

Benign infantile familial convulsions (BIFC) and benign familial neonatal convulsions (BFNC) are two forms of familial convulsions having an age of onset within the first year of life. The gene responsible for BFNC has been mapped to chromosome 20q in the close vicinity of D20S19 and D20S20 markers. We performed linkage analysis between BIFC and D20S19–D20S20 in eight families in order to know whether the BFNC gene is also implicated in BIFC. Several apparent obligate crossovers between affected members were detected. The data here presented demonstrate that the BFNC gene is not responsible for BIFC.
Zoster sine herpete, A clinical variant
Authors: Gilden Donald H. , Wright Roy R. , Schneck Stuart A. , Gwaltney Jack M. , Mahalingam Ravi
Published: January 2005

Two otherwise healthy immunocompetent men, ages 62 and 66 years, experienced years of radicular pain without zoster rash. An extensive search for systemic disease and malignancy was negative. Varicella‐zoster virus DNA, but not herpes simplex virus DNA, was found in the cerebrospinal fluid of the first patient 5 months after the onset of pain, and in the second patient 8 months after the onset of pain. Prolonged radicular pain without zoster rash combined with the presence of varicella‐zoster virus in the cerebrospinal fluid indicates that both men had zoster sine herpete, and strongly supports this syndrome as a clinical variant.
Hereditary motor and sensory neuropathy with calf hypertrophy is associated with 17p 11.2 duplication
Authors: Uncini A. , Di Muzio A. , Chiavaroli F. , Gambi D. , Sabatelli M. , Archidiacono N. , Antonacci R. , Marzella R. , Rocchi M.
Published: January 2005

The demyelinating type of hereditary motor and sensory neuropathy (HMSN I) is characterized by progressive weakness and atrophy of leg muscles. Six patients (age, 25–79 yr) belonging to three generations had calf hypertrophy (6 of 6), foot drop or difficulty with heel walking (4 of 6), pes cavus (3 of 6), absent or depressed tendon jerks in the lower limbs (4 of 6), and mild distal sensory loss (3 of 6). No other family member had leg atrophy. Motor conduction velocities ranged from 20 to 40 m/sec. Sural nerve biopsy showed loss of large myelinated fibers, numerous onion bulbs, and segmental demyelination and remyelination. Computed tomographic scans of leg muscles and histological and morphometric findings in gastrocnemius revealed true muscular hypertrophy. Southern blot and fluorescence in situ hybridization documented the duplication of the entire 17p11.2 segment associated with classical HMSN IA. The pathogenesis of muscle hypertrophy in our cases is unclear. Chronic leg muscle weakness and long‐standing partial denervation might cause calf enlargement by a combination of compensatory “work‐induced” and “stretch‐induced” fiber hypertrophy. Alternatively, that all the affected family members presented calf hypertrophy might suggest the action of a genetic factor associated with the duplication at 17p11.2.
Nerve biopsy findings in different patterns of proximal diabetic neuropathy
Authors: Said Gérard , Goulon‐Goeau Catherine , Lacroix Catherine , Moulonguet Antoine
Published: January 2005

Besides distal symmetrical sensory polyneuropathy (DSSP), middle‐aged diabetic patients may present with focal or multifocal neuropathies, including proximal neuropathy of the lower limbs, the pathophysiological features of which are uncertain. We studied 10 non–insulin‐dependent diabetic patients, 45 to 72 years of age, who developed a painful proximal neuropathy of the lower limbs for which other causes of neuropathy were carefully excluded. The proximal neuropathy was asymmetrical in all patients, sensory in 4, motor and sensory in the others. Signs of DSSP were present in all. A sample of the intermediate cutaneous nerve of the thigh, a sensory branch of the femoral nerve, was taken by biopsy and examined by light and electron microscopy. Examination of the nerve specimens revealed ischemic nerve lesions in 3 patients. Nerve ischemia was associated with vasculitis and inflammatory infiltration in 2 of them. In the other patients the lesions of the cutaneous nerve of the thigh included a varying incidence of axonal and demyelinative lesions similar to those observed in DSSP, with mild inflammatory infiltration in 4 of them. The density of myelinated and of unmyelinated was variably decreased. This study shows that axonal and demyelinative lesions similar to those found in diabetic DSSP are present in proximal nerves in mild forms of proximal diabetic neuropathy; while nerve ischemia, inflammatory infiltration, and vasculitis are encountered in the most severe forms of proximal diabetic neuropathy.
Correlation of clinical features and findings on cranial magnetic resonance imaging with urinary myelin basic protein‐like material in patients with multiple sclerosis
Authors: Whitaker John N. , Williams Paula H. , Layton Beverly A. , McFarland Henry F. , Stone Lael A. , Smith M. E. , Kachelhofer R. David , Bradley Edwin L. , Burgard Sheila , Zhao Guojun , Paty Donald W.
Published: January 2005

Immunoreactive material that appears to be a peptide encompassing all or a portion of residues 80 to 89 of myelin basic protein is present in normal unconcentrated urine and is increased in certain patients with multiple sclerosis (MS). Compared with normal controls, urines collected randomly from 158 MS patients or in a clinical research unit from 8 patients with MS had higher mean values of urinary MBP‐like material (MBPLM). The level of MBPLM in urine showed no direct relationship to MBPLM in cerebrospinal fluid and did not correlate with clinical relapses of disease. In the other neurological disease control group (26 patients), some patients with other inflammatory diseases, but not stroke or early phase Guillain‐Barré syndrome, also showed elevations. Among the subtypes of MS, those with secondary chronic progressive disease had the highest values. Urinary MBPLM showed no definite correlation with or effect of treatment with glucocorticoids and immunosuppressants except that a lower level of urinary MBPLM showed a weak relationship with improvement following treatment with methylprednisolone/prednisone. In a serial study of 8 patients with unenhanced cranial magnetic resonance imaging and 20 patients with gadolinium‐enhanced cranial magnetic resonance imaging, urinary MBPLM did not show a direct correlation with new or enhancing lesions. Urinary MBPLM does not parallel acute myelin damage but appears to reflect an ongoing process, possibly linked to attempted efforts at remyelination.
Elevated central nervous system prostaglandins in human immunodeficiency virus—associated dementia
Authors: Griffin Diane E. , Wesselingh Steven L. , McArthur Justin C.
Published: January 2005

The dementia associated with human immunodeficiency virus (HIV) is poorly understood. Dementia is accompanied by infection and activation of macrophage lineage cells in the brain and production of toxic products by these cells has been postulated to play a role in the pathogenesis of dementia. Eicosanoids are potential products of activated macrophages that can mediate cell injury. We measured the levels of prostaglandin E2 in the cerebrospinal fluid of HIV‐positive individuals with dementia and/or myelopathy and compared these levels with those of HIV‐negative patients with other neurological diseases and HIV‐positive patients without dementia. Cerebrospinal fluid prostaglandin E2 levels were increased in dementia. This increase was associated with severity of dementia and correlated with cerebrospinal fluid levels of neopterin and β2‐microglobulin. Prostaglandins F2α and thromboxane B2, additional products of the cyclooxygenase pathway of arachidonic acid metabolism, were also elevated in dementia, but leukotriene C4, a product of the lipoxygenase pathway was not. Since synthesis of prostaglandins is regulated in part by the levels of inducible forms of cyclooxygenase, we measured the levels of cyclooxygenase‐1 and 2 mRNAs in the brains of HIV‐positive individuals with and without dementia by reverse transcriptase polymerase chain reaction. Levels of intact cyclooxygenase‐1 mRNA were higher in the brains of demented individuals, but this did not reach statistical significance. These data demonstrate that prostaglandins are increased in the central nervous system in HIV‐associated dementia and may play a role in the development of neurological dysfunction.
Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis
Authors: Dyck Peter James , Litchy William J. , Minnerath Sharon , Bird Thomas D. , Chance Phillip F. , Schaid Daniel J. , Aronson Arnold E.
Published: January 2005

We describe two kindreds with an autosomal dominant inherited disorder characterized by a variable degree of muscle weakness of limbs, vocal cords, and intercostal muscles and by asymptomatic sensory loss, beginning in infancy or childhood in severely affected persons. Life expectancy in severely affected patients is shortened because of respiratory failure. Because nerve conduction velocities are normal and it is an inherited axonal neuropathy, we classify the disorder as a variety of hereditary motor and sensory neuropathy type II (HMSN II) (HMSN IIc). The present report provides further evidence for heterogeneity among the hereditary motor and sensory neuropathy type II disorders. In one large pedigree with the type IIc disorder, no linkage to DNA markers known to map near the HMSN IA locus on chromosome 17p or the HMSN IB locus on chromosome 1q was demonstrated.
Parkinsonism induced by solvent abuse
Authors: Uitti Ryan J. , Snow Barry J. , Shinotoh Hitoshi , Vingerhoets Francois J. G. , Hayward Margo , Hashimoto Stanley , Richmond John , Markey Sanford P. , Markey Carol J. , Calne Donald B.
Published: January 2005

We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits wee indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals.
Absence of postoperative hyponatremia syndrome in young, healthy females
Authors: Wijdicks Eelco F. M. , Larson Timothy S.
Published: January 2005

Young and previously healthy females have been reported to develop severe postoperative hyponatremia with a fatal outcome. The clinical presentation is dramatic, with seizures, respiratory arrest, and permanent, often catastrophic, brain damage. The true incidence is unknown. We report a survey of 290,815 surgical procedures on females at the Mayo Clinic from 1976 to 1992. Postoperatively 1,498 females had cardiopulmonary arrest, 255 had a metabolic encephalopathy, 32 had new‐onset seizures, and 6 had central pontine myelinolysis. We failed to identify any association of respiratory arrest with postoperative hyponatremia. Our findings indicate that the postoperative hyponatremia syndrome in young, healthy females with respiratory arrest is extremely uncommon.
Neurological complications from fat emulsion therapy
Authors: Schulz Paul E. , Weiner Susan P. , Haber Leslie M. , Armstrong Dawna D. , Fishman Marvin A.
Published: January 2005

Fat emulsion therapy is convenient for parenterally administering calories and essential fats. We report 2 children with neurological complications of fat emulsion therapy that arose before any systemic findings. The complications included focal and generalized seizures, weakness, and altered mental status. Biopsy and autopsy findings included cerebral endothelial and intravascular lipid deposition. Early recognition of fat emulsion therapy complications is essential as the neurological complications are potentially reversible with alteration of the parenteral diet.
Diagnosis of Epstein‐Barr virus–induced central nervous system infections by DNA amplification from cerebrospinal fluid
Authors: Landgren Magnus , Kyllerman Mårten , Bergström Tomas , Dotevall Leif , Ljungström Lars , Ricksten Anne
Published: January 2005

A nested polymerase chain reaction was used for the detection of Epstein‐Barr virus DNA in 1 patient with encephalitis, and in 1 patient with myelitis. Epstein‐Barr virus DNA was detected in cerebrospinal fluid samples obtained at the onset of neurological symptoms in both patients, and serological findings indicated ongoing Epstein‐Barr virus infection. In the patient with encephalitis, herpes simplex virus type 1 DNA was transiently detected in the cerebrospinal fluid, while Epstein‐Barr virus DNA was still present on day 44 after admittance. Single‐photon emission computed tomography in this patient indicated a frontal bilateral hypoperfusion. The diagnostic value of polymerase chain reaction on cerebrospinal fluid and serum samples for Epstein‐Barr virus infections of the central nervous system is emphasized.
Course and outcome of acute cerebellar ataxia
Authors: Connolly Anne M. , Dodson W. Edwin , Prensky Arthur L. , Rust Robert S.
Published: January 2005

We report a study of 73 consecutive children with acute cerebellar ataxia, representing all of the children evaluated at St. Louis Children's Hospital during a 23‐year‐period to whom this diagnosis could appropriately be assigned. Twenty‐six percent had chickenpox, 52% had other illnesses that were presumed to be viral, and in 3% the ataxia was related to immunization. Nineteen percent had no definite prodrome. Sixty children were followed for 4 months or longer after onset of their ataxia (mean, 7.4 ± 6.0 years). Ninety‐one percent (55/60) of these, including all children with chickenpox, recovered completely from ataxia. Eighty‐nine percent (39/44) of the children with non‐varicella‐related ataxia recovered completely from the ataxia, a much better rate of recovery than what was found in prior large studies. One fifth of the children followed for more than 4 months experienced transient behavioral or intellectual difficulties, but only 5 of the 60 children demonstrated sustained learning problems. This study represents the largest reported series of acute cerebellar ataxia and the most complete characterization of the clinical features and outcome of this illness.
Monoclonal IgM antibodies to GM1 and asialo‐GM1 in chronic neuropathies cross‐react with Compylobacter jejuni lipopolysaccharides
Authors: Wirguin I. , Suturkova‐Milosevic Lj. , Della‐Latta P. , Fisher T. , Brown R. H. , Latov N.
Published: January 2005

We tested monoclonal IgM anti‐GM1 and asialo‐GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysccharides (LPS) from three strains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme‐linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo‐GM1, or blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti‐GM1 or anti–asialo‐GM1 antibodies cross‐react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti‐GM1 antibodies.
Deletion in the CMT1A locus on chromosome 17p11.2 in hereditary neuropathy with liability to pressure palsies
Authors: Verhalle D. , Löfgren A. , Nelis E. , Dehaene I. , Theys P. , Lammens M. , Dom R. , Van Broeckhoven C. , Robberecht W.
Published: January 2005

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease of peripheral nerves, characterized by recurrent focal neuropathies often with an underlying asymptomatic polynuropathy. We report the clinical, electrophysiological, and histopathological findings in three families with HNPP and confirm the presence of a deletion on chromosome 17p11.2, including all the markers known to be duplicated in Charcot‐Marie‐Tooth disease type 1A. This deletion appears to be the underlying molecular deficit in this disease and provides additional evidence for the importance of this locus for peripheral nerve function.
Brain morphology in normal and dyslexic children: The influence of sex and age
Authors: Schultz Robert T. , Cho Nam K. , Staib Lawrence H. , Kier Leon E. , Fletcher Jack M. , Shaywitz Sally E. , Shankweiler Donald P. , Katz Len , Gore John C. , Duncan James S. , Shaywitz Bennett A.
Published: January 2005

Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5–9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia.
Seizure exacerbation and status epileptics related to carbamazepine‐10,11‐epoxide
Authors: So Elson L. , Ruggles Kevin H. , Cascino Gregory D. , Ahmann Peter A. , Weatherford Karen W.
Published: January 2005

Over a 3‐year period, we encountered 6 adults whose seizure control unexpectedly deteriorated with the occurrence of partial status epilepticus and daily multiple seizures. Analysis of the case histories and subsequent clinical follow‐up for 1 1/2 to 3 years disclosed the following evidence that demonstrates the role of carbamazepine‐epoxide in the development of the seizure exacerbation: (1) There were high serum carbamazepine‐epoxide concentrations while serum carbamazepine concentrations were lower than or the same as baseline levels; (2) all patients were taking drugs that are known to increase serum carbamazepine‐epoxide concentrations; (3) status epilepticus failed to respond to intravenous phenytoin loading; (4) seizure exacerbation in all patients was corrected by withholding carbamazepine dose; (5) seizure exacerbation recurred in 1 patient who resumed the same dose of carbamazepine; and (6) there were no prior status epilepticus or daily multiple seizures despite previous toxicities with other antiepileptic drugs in 3 patients. Our experience shows that inconspicuous elevation of carbamazepine‐epoxide levels during polytherapy may precipitate a distinct state of drug toxicity characterized by severe exacerbation of seizures. Mental retardation may be a predisposition to this condition.
Parceling of mesial frontal motor areas during ideation and movement using functional magnetic resonance imaging at 1.5 tesla
Authors: Tyszka J. M. , Grafton S. T. , Chew W. , Woods R. P. , Colletti P. M.
Published: January 2005

Finger movement–related responses were identified in there discrete sites of mesial frontal cortex in 7 normal subjects using high resolution functional magnetic resonance imaging. During imagination of the same movements there was a differential response with rostral areas more active than caudal areas. Humans have multiple motor areas in mesial frontal cortex that subserve different functions in motor planning and execution.
Treatment of Guillain‐Barré syndrome with high‐dose immune globulins combined with methylprednisolone: A pilot study
Authors:   The Dutch Guillain‐Barré Study Group
Published: January 2005

In an open study 25 patients with Guillain‐Barré syndrome were treated for 5 days with intravenous immune globulins in a dose of 0.4 gm/kg of body weight/day and 0.5 gm of methylprednisolone intravenously per day. The results of this combined treatment were compared with the results from a group of 74 patients who were treated with immune globulins only in a recent Dutch Guillain‐Barré trial. In the methylprednisolone–immune globulin treatment group, 19 of 25 patients (76%) improved by one or more functional grades after 4 weeks, as compared with 39 (53%) of 74 patients treated with immune globulin alone (p = 0.04). Also the median time required to the stage of walking independently was reduced in the methylprednisolone–immune globulin treatment group. This pilot study suggests that combined treatment with methylprednisolone and immune globulins in patients with the Guillain‐Barré syndrome is more effective than treatment with immune globulins alone; a randomized clinical trial might confirm this.
Cerebrospinal fluid human immunodeficiency virus type 1 (HIV‐1) p24 antigen levels in HIV‐1–related dementia
Authors: Royal W. , Selnes O. A. , Concha M. , Nance‐Sproson T. E. , McArthur J. C.
Published: January 2005

Human immunodeficiency virus type 1 (HIV‐1) p24 antigen, a putative marker of virus load, was assayed in 79 blood and 83 cerebrospinal fluid (CSF) samples from 90 HIV‐1–seropositive individuals with or without demetia. Twenty‐eight subjects had no evidence of neuropsychological impairment, 17 had mild impairment without objective evidence of dementia, and 45 were demented. HIV‐1 p24 antigen was detected more frequently in CSF samples from demented (19/40) than normal (1/26) or mildly impaired (1/17) subjects and in 67% of individuals with significant dementia (MSK stages 2–4). p24 Antigen was detected less frequently in CSF from demented subjects on antiretroviral drugs than untreated demented individuals. Overall, the sensitivity of the antigen capture assay in CSF among demented individuals was 47.5%; the specificity, 95.0%; positive predictive value, 90.4%; negative predictive value, 66.1%; and the efficieny, 72.2%. A direct relationship was also noted between the degree of congnitive impairment and blood p24 antigen detection frequency and antigen concentration. CD4+ blood lymphocyte counts were lower for demented individuals, and HIV‐1 p24 antigen was detected more frequently and p24 antigen concentration was higher in blood and CSF from individuals with low CD4+ blood lymphocyte counts. β2‐Microglobulin levels were higher in CSF from demented subjects and correlated directly with CSF p24 antigen concentration. However, in contrast to CD4+ blood lymphocyte counts and β2‐microglobulin levels, only p24 antigen concentration correlated with dementia severity. Therefore, p24 antigen can be a useful marker for dementia related to HIV‐1 infection.
Cognitive functions and quality of life in patients with low‐grade gliomas: The impact of radiotherapy
Authors: Taphoorn M. J. B. , Schiphorst A. Klein , Snoek F. J. , Lindeboom J. , Wolbers J. G. , Karim A. B. M. F. , Huijgens P. C. , Heimans J. J.
Published: January 2005

The role of early radiotherapy in the treatment of low‐grade gliomas is controversial. For this reason the impact of radiotherapy on quality of life was studied in long‐term survivors of biopsy‐proved low‐grade gliomas without signs of tumor recurrence. Twenty patients (age range, 18–66 years) had been treated with early radiotherapy; the other 21 patients (age range, 19–65 years) had undergone surgery or biopsy only. The interval from diagnosis to testing ranged from 1 to 12 years (mean, 3.5 years). Nineteen patients with low‐grade hematological malignancies, surviving 1 to 15 years without central nervous system involvement, served as control subjects. Apart from the neurological and functional status, the patients' cognitive, affective, and psychological status was determined. None of the survivors had significant neurological impairment and the Karnofsky index for them was at least 70. However, more specific examinations of cognitive functions and the affective status (Profile of Mood States) indicated that, compared to the control subjects, the patients with low‐grade gliomas had significantly more cognitive disturbances and suffered more frequently from fatigue and depressed moods. The two groups with low‐grade gliomas, on the other hand, did not differ significantly on any of these measures. It is concluded that radiotherapy did not cause these disturbances and had no negative impact on quality of life in these patients.
Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy
Authors: Litvan I. , Blesa R. , Clark K. , Nichelli P. , Atack J. R. , Mouradian M. M. , Grafman J. , Chase T. N.
Published: January 2005

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose‐response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physo‐stigmine). Physostigmine had no significant neurobehavioral effects at any does in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High‐dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be terapeutically ineffective.
Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis
Authors: Arnold Douglas L. , Riess Gerald T. , Matthews Paul M. , Francis Gordon S. , Collins D. Louis , Wolfson Christina , Antel Jack P.
Published: January 2005

Decreases in brain N‐acetylasparatate are associated with neuronal loss or dysfunction. We report a longitudinal study in which changes in the N‐acetylaspartate to creatine resonance intensity ratio measured by brain proton magnetic resonance spectroscopy were used to follow the progression of brain pathology in 7 patients with multiple sclerosis over an 18‐month period. Four of the patients had a history of recurrent relapses and 3 had a secondary progressive course. All had clinical and magnetic resonance imaging evidence of persistent neurological abnormalaties. At 6‐month intervals proton magnetic resonance spectra were obtained and the N‐acetylaspartate–creatine ratio was determined for each patient. The volumes of hyperintense signal from lesions on conventional magnetic resonance images and the Kurtzke Expanded Disability Status Scale scores were determined concurrently. At the onset of the study, the N‐acetylaspartate–creatine ratio was significantly (p < 0.05) lower in the central brain volumes from the patients than in 13 normal control subjects. At 12 and 18 months of follow‐up, the ratio had decreased further in all patients (p < 0.05), consistent with progressive accumulation of neuronal damage. In contrast to magnetic resonance spectra data, changes in lesion volume on magnetic resonance images or disability status did not reach significance over this period. Subgroup analysis showed that changes (increases or decreases) in the N‐acetylaspartate–creatine ratio between consecutive 6‐month examinations correlated significantly (r = –0.74, p < 0.005) with changes in lesion volume on magnetic resonance images in patients with a history of relapses. This pilot study suggests that proton magnetic resonance spectroscopy may be useful in evaluating the progression of cerebral damage in multiple sclerosis using a novel quantitative index based on neuronal damage or dysfunction.
Leber's hereditary optic neuropathy mitochondrial DNA mutations in multiple sclerosis
Authors: Kellar‐Wood H. , Robertson N. , Govan G. G. , Compston D. A. S. , Harding A. E.
Published: January 2005

The observation of a multiple sclerosis (MS)–like illness in patients, particularly women, who carry the most common Lber's hereditary optic neuropathy mitochondrial DNA (mtDNA) mutation may indicate a contributory role for mitochondrial genes in genetic susceptibility to MS. We screened 307 unrelated MS patients, ascertained from population surveys, for the pathogenic Leber's hereditary optic neuropathy mutations at positions 11778 and 3460 of mt DNA, and also studied 20 patients with prominent and early optic nerve involvement. In addition, these 307 patients and 129 control subjects were investigated for the base change at position 13708, which has been suggested to paly a role in the pathogenesis of Leber's hereditary optic neuropathy. Neither of the pathogenic mtDNA mutations occured in the unselected MS patients. The 13708 base change was present in MS patients at a frequency similar to that in healthy control subjects. Three of the patients selected on the basis of severe optic nerve involvement had either the 11778 (one) or 3460 (two) mutations associated with Leber's herediatary optic neuropathy. All were women and none had affected relatives. We conclude that these mutations do not contribute to genetically determined susceptibility in typical MS patients, although a mitochondrial genetic component in the etiology of MS remains possible. A subgroup of MS patients, particularly females with severe bilateral visual failure due to optic neuropathy, may harbor a Leber's hereditary optic neuropathy mutation and we suggest that mtDNA analysis is appropriate in these patients.
Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy
Authors: Gilman Sid , Koeppe Robert A. , Junck Larry , Kluin Karen J. , Lohman Mary , St. Laurent Roy T.
Published: January 2005

We used positron emission tomography with [18F] fluorodeoxyglucose to study local cerebral metabolic rates for glucose (ICMRglc) in patients with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA) in comparison with normal control subjects. In MSA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In sOPCA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In dOPCA, absolute lCMRglc was significantly decreased in the brainstem and cerebellum but not in the other structures. Examination of lCMRglc normalized to the cerebral cortex in comparison with normal controls revealed in MSA significant decreases in the brainstem, cerebellum, and putamen but, in both sOPCA and dOPCA, significant decreases only in the brainstem and cerebellum. The findings indicate that these three disorders all show a marked decrease of lCMRglc in the brainstem and cerebellum but differ in the degree of hypometabolism in forebrain and cerebral cortical structures. The results are consistent with the possibility that, in many cases, sOPCA will evolve into MSA. Moreover, positron emission tomography may provide helpful diagnostic information in these neurodegenerative diseases.
Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy
Authors: Kastner A. , Herrero M. T. , Hirsch E. C. , Guillen J. , Luquin M. R. , Javoy‐Agid F. , Obeso J. A. , Agid Y.
Published: January 2005

Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.
Syncope: A videometric analysis of 56 episodes of transient cerebral hypoxia
Authors: Lempert T. , Bauer M. , Schmidt D.
Published: January 2005

To investigate the clinical features of transient cerebral hypoxia, syncope was induced in 56 of 59 healthy volunteers through a sequence of hyperventilation, orthostasis, and Valsalva maneuver. All events were monitored on video by two cameras. Complete syncope with falling and loss of consciousness was observed in 42 subjects, lasting 12.1 ± 4.4 seconds. Myoclonic activity occurred in 38 of these 42 episodes (90%). The predominant movement pattern consisted of multifocal arrhythmic jerks both in proximal and distal muscles. Superposition of generalized myoclonus was common. Additional movements such as head turns, oral automatisms, and righting movements occurred in 79%. Eyes remained open throughout syncope in most subjects and initial upward deviation was common. Sixty percent reported visual and auditory hallucinations. Thirteen subjects had incomplete syncope with falls but partially preserved consciousness. These episodes were shorter and usually not accompanied by myoclonus and hallucinations. Transient amnesia and unresponsiveness without falling occurred in 1 subject.
Decreased dopamine transporters with age in healthy human subjects
Authors: Volkow N. D. , Fowler J. S. , Wang G. J. , Logan J. , Schlyer D. , MacGregor R. , Hitzemann R. , Wolf A. P.
Published: January 2005

The effects of aging on brain dopamine transporters was evaluated in 26 healthy male volunteers (age range, 21–63 years) using positron emission tomography and [11C]cocaine. The ratio of the distribution volume for [11C]cocaine in basal ganglia to that in cerebellum was used as a model parameter for dopamine transporter availability and showed a significant negative correlation with age (r = 0.65, p < 0.0005). This results document an age‐related decline in dopamine transporters in healthy individuals.
In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging
Authors: Husted C. A. , Matson G. B. , Adams D. A. , Goodin D. S. , Weiner M. W.
Published: January 2005

The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal‐appearing white matter by evaluating the spectral broad component from phosphorus 31 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p <001) in both lesions and in normal‐appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times.
Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia
Authors: Sian Jeswinder , Dexter David T. , Lees Andrew J. , Daniel Susan , Agid Yves , Javoy‐Agid France , Jenner Peter , Marsden C. David
Published: January 2005

Reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured in various brain areas (substantia nigra, putamen, caudate nucleus, globus pallidus, and cerebral cortex) from patients dying with Parkinson's disease, progressive supranuclear palsy, multiple‐system atrophy, and Huntington's disease and from control subjects with no neuropathological changes in substantia nigra. GSH levels were reduced in substantia nigra in Parkinson's disease patients (40% compared to control subjects) and GSSG levels were marginally (29%) but insignificantly elevated; there were no changes in other brain areas. The only significant change in multiple‐system atrophy was an increase of GSH (196%) coupled with a reduction of GSSG (60%) in the globus pallidus. The only change in progressive supranuclear palsy was a reduced level of GSH in the caudate nucleus (51%). The only change in Huntington's disease was a reduction of GSSG in the caudate nucleus (50%). Despite profound nigral cell loss in the substantia nigra in Parkinson's disease, multiple‐system atrophy, and progressive supranuclear palsy, the level of GSH in the substantia nigra was significantly reduced only in Parkinson's disease. This suggests that the change in GSH in Parkinson's disease is not solely due to nigral cell death, or entirely explained by drug therapy, for multiple‐system atrophy patients were also treated with levodopa. The altered GSH/GSSG ratio in the substantia nigra in Parkinson's disease is consistent with the concept of oxidative stress as a major component in the pathogenesis of nigral cell death in Parkinson's disease.
Voluntary movement at the elbow in spastic hemiparesis
Authors: Fellows S. J. , Kaus C. , Thilmann A. F.
Published: January 2005

The relative importance of hyperreflexia and paresis in disturbances of voluntary arm movement was studied in a group of patients (n = 25) with spasticity arising from a unilateral ischemic cerebral lesion. Patient performance was evaluated against data obtained from normal subjects (n = 15). Spastic patients achieved lower maximum movement velocities during flexion or extension than did normal subjects. The more marked the paresis of the elbow flexor and extensor muscles of the patients, relative to the strength of the normal subjects, the greater was this reduction in maximum velocity. For a given velocity, however, the time taken to complete a movement and the time to reach the peak velocity were normal. No relationship was found between the degree of impairment of voluntary movement and the level of passive muscle hypertonia in the antagonist. Although overactivity of the antagonist muscle may play some role in disturbance of movements made at low velocities without an opposing load, antagonist activity during movements made against a load (i.e., under more natural conditions) was at or below normal levels, even in those patients with the most marked passive muscle hypertonia. It is concluded that agonist muscle paresis, rather than antagonist muscle hypertonia, plays the dominant role in the disturbance of voluntary elbow movement following stroke.
Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus
Authors: Giannini Caterina , Dyck Peter James
Published: January 2005

We evaluated 433 transversely sectioned microvessels from 54 sural nerves of diabetic patients with (43) and without (11) polyneuropathy and compared the findings with those of 366 microvessels from 50 sural nerves from controls, spanning the same ages. Whereas the number of microvessels per square millimeter and lumen areas and their size distribution were not significantly different between diabetic patients and controls, striking changes of the vessel wall were found in the nerves of diabetic patients. Mural area containing reduplicated basement membranes and pericyte degeneration were significantly increased in diabetic when compared with control nerves. A very low frequency of microvessel degeneration and endothelial cell separation was also encountered but only in diabetics with polyneuropathy. The microvessel changes we have found in nerve largely confirm and strengthen our previous findings. This study provides additional strong support for the idea that the mural changes of endoneurial microvessels do not relate to aging but do relate to diabetes mellitus. The structural alterations of endoneurial microvessel mirror changes seen in diabetic retinopathy and are sufficiently severe that they may accompany and account for functional alterations of the blood–nerve barrier and endoneurial microenvironment. It remains to be shown whether and how these changes relate to the development of polyneuropathy.
Homozygous inheritance of the Machado‐Joseph disease gene
Authors: Lang Anthony E. , Rogaeva E. A. , Tsuda T. , Hutterer J. , St George‐Hyslop Peter
Published: January 2005

We report a patient presenting at age 16 years with postural instability and falls who developed severe generalized dystonia by the age of 20 years. He was the product of a consanguineous marriage. Maternal grandfather and paternal grandmother (brother and sister) living in the Azores were both affected by Machado‐Joseph disease (MJD) beginning late in life. To date neither of the patient's parents are clinically affected. Linkage studies in this family and others of Azorean descent have confirmed the recent mapping of the MJD gene to chromosome 14q. Genotyping of the members of this pedigree provides strong genetic evidence that our patient is homozygous for the MJD gene. Our results combined with experience in 2 putative homozygotes previously reported in the literature suggest that gene dosage is an important determinant of age of onset and clinical phenotype in MJD. Other possible influencing factors are discussed.
Effects of edrophonium on saccadic velocity in normal subjects and myasthenic and nonmyasthenic ocular palsies
Authors: Barton Jason J. S. , Huaman Ana G. , Sharpe James A.
Published: January 2005

We measured saccadic peak velocities in 8 patients with myasthenia gravis, 9 patients iwth proven nonmyasthenic ocular palsies, and 3 controls. Patients followed a target moving to and from primary position at 1‐second intervals for 8 minutes. We measured the amplitudes and velocities of centrifugal saccades at the start of the task, after 3 minutes of the task (fatigue) and 1 minute after receiving IV edrophonium. The effects of fatigue, though prominent in some myasthenic patients, did not distinguish between the groups. However, edrophonium increased saccadic peak velocities in myasthenic patients but decreased them in both controls and nonmyasthenic patients. Analysis of saccades by amplitude bins showed that these changes in peak velocity reflected shifts in the velocity–amplitude relationship.
Magnetic stimulation of corticospinal pathways at the foramen magnum level in humans
Authors: Ugawa Yoshikazu , Uesaka Yoshikazu , Terao Yasuo , Hanajima Ritsuko , Kanazawa Ichiro
Published: January 2005

Magnetic stimulation done with a double cone coil placed over the back of the head activated descending motor pathways and produced electromyographic responses in muscles of the arms and legs. The latencies of these responses were the same as those of responses to electrical brainstem stimulation. The threshold was lowest when the coil was placed over the inion or below it on the median line. Placement of the coil on the side ipsilateral to the muscle was more effective than placement on the contralateral side. These results indicate that activation occurs at the foramen magnum level (just below the pyramidal decussation). Collision experiments that used cortical and magnetic brainstem stimulation indicated that the major part of the responses to the latter stimulation were conducted via the large diameter component of the corticospinal tract. Collision experiments done with the peripheral nerve and magnetic brainstem stimulation showed that this stimulation produced a single descending volley in the descending tract. We conclude that magnetic brainstem stimulation produces a single descending volley in the corticospinal tract at the foramen magnum level with less discomfort.