bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency and distribution of Alzheimer's disease in Europe: A collaborative study of 1980–1990 prevalence findings
Authors: Rocca Walter A. , Hofman Albert , Brayne Carol , Breteler Monique M. B. , Clarke Michael , Copeland John R. M. , Dartigues Jean‐Francois , Engedal Knut , Hagnell Olle , Heeren Thea J. , Jonker Cees , Lindesay James , Lobo Antonio , Mann Anthony H. , Mölsä Pekka K. , Morgan Kevin , O'Connor Daniel W. , Droux Arnaldo da Silva , Sulkava Raimo , Kay David W. K. , Amaducci Luigi
Published: January 2005

We reanalyzed and compared current prevalence estimates of Alzheimer's disease in Europe. Studies characterized as follows qualified for comparison: dementia defined by the Diagnostic and Statistical Manual for Mental Disorders, 3rd edition, or equivalent criteria; Alzheimer's disease diagnosed by the National Institute of Neurological and Communicative Disorders and Stroke‐Alzheimer's Disease and Related Disorders Association or equivalent criteria; case‐finding through direct individual examination; appropriate sample size; and inclusion of institutionalized persons. Of the 23 European surveys of dementia considered, six fulfilled the inclusion criteria. When age and sex were considered, there were no major geographic differences in the prevalence of Alzheimer's disease across Europe. Overall European prevalence (per 100 population) for the age groups 30 to 59, 60 to 69, 70 to 79, and 80 to 89 years was, respectively, 0.02, 0.3, 3.2, and 10.8. Prevalence increased exponentially with advancing age and, in some populations, was consistently higher in women. Prevalence remained stable over 15 years in one study.
Etiology of motor or sensory stroke: A prospective study of the predictive value of clinical and radiological features
Authors: Chimowitz M. I. , Furlan A. J. , Sila C. A. , Paranandi L. , Beck G. J.
Published: January 2005

The diagnostic utility of clinical and radiological features for distinguishing penetrating artery disease from other causes of stroke has been questioned. To address this issue, we prospectively evaluated more than 40 features in 85 patients with pure motor, sensorimotor, or pure sensory syndromes. Nonischemic causes were present in 4 patients. The causes of ischemic stroke in the other 81 patients were penetrating artery disease (32 patients), large artery occlusive disease (17), cardioembolism (12), other causes (8), and undetermined (12). Of the features evaluated, frequent transient ischemic attacks (≥ 1/day), transient ischemic attacks occurring only within 1 week of stroke, pure motor hemiparesis (similar involvement of face, arm, and leg), pure sensory stroke, and round or oval infarction were associated (p< 0.05) with penetrating artery disease. However, only pure sensory stroke involving two or more regions of the body and pure motor hemiparesis associated with subcortical infarction of less than 1.5 cm had positive predictive values exceeding 90% for penetrating artery disease. Carotid bruit ipsilateral to an anterior circulation in farction, monoparesis, and striatocapsular infarction had positive predictive values exceeding 90% for causes other than penetrating artery disease; however, half of the striatocapsular infarctions were of undetermined cause. These data suggest that certain clinical and radiological features are useful for distinguishing penetrating artery disease from other causes of stroke.
Preproenkephalin messenger RNA—containing neurons in striatum of patients with symptomatic and presymptomatic huntington's disease: An in situ hybridization study
Authors: Albin Roger L. , Qin Ying , Young Anne B. , Penney John B. , Chesselet Marie‐Francoise
Published: January 2005

Previous studies have revealed a loss of enkephalin immunoreactivity in the terminals of striatal neurons projecting to the external globus pallidus in patients with early grades of Huntington's disease (HD). To assess the status of the perikarya of striatal enkephalinergic neurons, we performed in situ hybridization histochemistry with a radiolabeled RNA probe complementary to preproenkephalin messenger RNA. We studied postmortem brain tissue of 6 patients with symptomatic HD, 7 control subjects, and 2 presymptomatic carriers of the HD allele. There was a significant reduction in the areal density of striatal neurons expressing preproenkephalin messenger RNA in the patients with symptomatic HD, but the level of labeling in the remaining cells was not altered compared with the control subjects. In the specimens from presymptomatic individuals, there was no reduction of areal density of preproenkephalin messenger RNA‐containing neurons in the striatum, despite the fact that loss of enkephalin immunoreactivity in the external globus pallidus had been previously demonstrated in the same brains. The results correlate with the previous demonstration of depleted enkephalin immunoreactive terminals in the external globus pallidus in patients with symptomatic HD. They also suggest that the early loss of enkephalin immunoreactivity observed in the external globus pallidus of presymptomatic carriers of the HD allele is not related to a generalized death of striatal enkephalinergic neurons early in the course of the disease.
Cerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study
Authors: Vonsattel Jean Paul G. , Myers Richard H. , Tessa Hedley‐Whyte E. , Ropper Allan H. , Bird Edward D. , Richardson Edward P.
Published: January 2005

To identify those factors associated with cerebral hemorrhage among brains with cerebral amyloid angiopathy (CAA), we undertook a comparative postmortem histopathological study of amyloid‐containing vessels in the brains of patients with and without hemorrhage. Those without hemorrhage were represented by the following two groups: (1) elderly patients from a large general hospital (n = 66; age range, 75–107 years) and (2) patients with various neuropsychiatric disorders (n = 70; age range, 27–96 years). CAA was found in 45% of thefirst group and in 54% of the second group. The findings in these patients were compared with those in 17 brains in which both CAA and cerebral hemorrhage were present. We found that CAA was more severe in the brains with cerebral hemorrhage than in those without, and that fibrinoid necrosis was seen only in the brains with cerebral hemorrhage (12 of the 17 brains). Microaneurysms occurred only in the presence of severe, rather than moderate or mild, CAA. Serial sections in 2 brains of patients with cerebral hemorrhage showed fibrinoid necrosis, microaneurysms, and vascular rupture in close association with the hemorrhage. In 2 patients, hemorrhage was precipitated by trauma, and in 1, it was secondary to metastatic carcinoma. The features of brains from patients with CAA that are most consistently related to cerebral hemorrhage are (1) a severe degree of CAA and (2) the presence of fibrinoid necrosis, with or without microaneurysms.
Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake
Authors: Stanley Charles A. , DeLeeuw Susan , Coates Paul M. , Vianey‐Liaud Christine , Divry Priscille , Bonnefont Jean‐Paul , Saudubray Jean‐Marie , Haymond Morey , Trefz Friedrich K. , Breningstall Galen N. , Wappner Rebecca S. , Byrd Dennis J. , Sansaricq Claude , Tein Ingrid , Grover Warren , Valle David , Rutledge S. Lane , Treem William R.
Published: January 2005

A defect in intracellular uptake of carnitine has been identified in patients with severe carnitine deficiency. To define the clinical manifestations of this disorder, the presenting features of 15 affected infants and children were examined. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation (median age of onset, 3 years). Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy had become apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes from patients. The defect also appears to be expressed in muscle and kidney. Concentrations of plasma carnitine and rates of carnitine uptake in parents were intermediate between affected patients and normal control subjects, consistent with recessive inheritance. Early recognition and treatmnent with high doses of oral carnitine may be life‐saving in this disorder of fatty acid oxidation.
Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene
Authors: Ebers G. C. , George A. L. , Barchi R. L. , Ting‐Passador S. S. , Kallen R. G. , Lathrop G. M. , Beckman J. S. , Hahn A. F. , Brown W. F. , Campbell R. D. , Hudson A. J.
Published: January 2005

The hyperkalemic periodic paralyses are a clinically heterogeneous group of autosomal dominant syndromes characterized by episodic paralysis associated with an elevated serum potassium level. Affected individuals in the same family tend to have homogeneous symptom complexes, although phenotypic variation is present among different families. For example, myotonia is absent in some pedigrees, present in others, and, in a third variant, paramyotonia congenita, myotonia coexists with cold‐induced paralysis. Electrophysiological studies have demonstrated variant‐specific abnormalities in skeletal muscle membrane sodium conductance. We tested the hypothesis that hyperkalemic periodic paralysis (without myotonia) and paramyotonia congenita are tightly linked to the tetrodotoxin‐sensitive adult skeletal muscle sodium channel gene on chromosome 17q23‐25 in two large pedigrees. The DNA polymorphisms detected in the growth hormone skeletal muscle sodium channel complex (GH1‐SCN4A) and by flanking polymorphic markers (D17S74 and D17S40) demonstrated no recombinants between the disease phenotypes and this complex. Phenotypic variation in the hereditary hyperkalemic periodic paralyses may result from allelic heterogeneity at the tetrodotoxin‐sensitive adult skeletal muscle sodium channel locus.
Occipital lobe epilepsy: Clinical characteristics, seizure spread patterns, and results of surgery
Authors: Williamson P. D. , Thadani V. M. , Darcey T. M. , Spencer D. D. , Spencer S. S. , Mattson R. H.
Published: January 2005

Twenty‐five patients with occipital lobe seizure origin were retrospectively evaluated to determine clinical seizure characteristics and electroencephalographic manifestations. Certain symptoms and signs served to identify occipital lobe origin in 22 (88%). These included elementary visual hallucinations, ictal amaurosis, eye movement sensations, early forced blinking or eyelid flutter, and visual field deficits. Eye or head deviation, or both, was observed frequently and was contralateral to the side of seizure origin in 13, but 3 patients exhibited ipsilateral deviation in some or all their seizures. After the initial signs and symptoms, clinical seizure characteristics resembled those of seizures originating elsewhere. Seizures typical of temporal lobe origin with loss of contact and various types of automatic, semipurposeful activity occurred in 11 patients. Seizures in 3 patients exhibited asymmetrical tonic or focal clonic motor patterns characteristic of frontal lobe seizures. Eleven of the 25 patients had, on two occasions, two or more distinctly different seizure types. Scalp electroencephalographic findings were seldom helpful for occipital lobe localization and were frequently misleading. Intracranial electroencephalographic recording correctly identified occipital lobe seizure origin in most, but not all, patients who had such studies. Intracranial electroencephalic recording also proved the variability in clinical seizure characteristics was related to different seizure spread patterns, medially or laterally above and below the sylvian fissure, both ipsilateral and contralateral to the occipital lobe of seizure origin. Eighteen patients had occipital lobe lesions detected with computed tomographic or magnetic resonance imaging scans or both. Resection of the lesions in 16 patients produced excellent results in 14 (88%). Five patients had temporal lobectomies, with good results in 3, but poor results in 2. Two patients with unlocalized seizures had complete section of the corpus callosum, 1 with a good result and the other with a poor result.
Progressive language disorder due to lobar atrophy
Authors: Snowden J. S. , Neary D. , Mann D. M. A. , Goulding P. J. , Testa H. J.
Published: January 2005

Sixteen patients with progressive language disorder have been studied longitudinally. Anomia was a prominent presenting characteristic and mutism ultimately occurred. Patients, however, were clinically heterogeneous. Some exhibited nonfluent, agrammatic features, whereas others demonstrated a fluent aphasia, with profound loss of word meaning. Although language disorder remained the sole symptom in a minority of patients, in others an associative agnosia or personality and behavioral changes, or both, emerged. Findings on computed tomography and single photon emission tomography mirrored the areas of dysfunction suggested by the neuropsychological profiles and demonstrated abnormalities restricted to the left hemisphere or involving bilateral frontotemporal cortices. Brains of 3 patients, with distinctive clinical pictures, have been examined at autopsy. Each revealed a focal distribution of atrophy, gliosis and spongiform change, and an absence of senile plaques and neurofibrillary tangles. There was clinical and pathological overlap with frontal lobe dementia. We argue that progressive language disorder is clinically heterogeneous and forms part of a spectrum of clinical presentations of non‐Alzheimer lobar atrophy.
Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease
Authors: Schellenberg Gerad D. , Boehnke Michael , Wijsman Ellen M. , Moore Deborah K. , Martin George M. , Bird Thomas D.
Published: January 2005

We previously reported a genetic association between the 3.5 kb (F) Taq I restriction fragment length polymorphism allele of the apolipoprotein CII gene on chromosome 19 and familial Alzheimer's disease. Here, we report an additional analysis of this association performed on an expanded and better defined data set of 23 families with familial Alzheimer's disease. The F allele frequency in affected family members in the expanded set was 0.62 ± 0.06 (mean ± standard error, n = 51 subjects), which differed significantly from a frequency of 0.39 ± 0.02 (n = 226) for unrelated control subjects (Z = 3.75, p < 0.0002). These results are consistent with our previous findings and suggest an association between the F allele of apolipoprotein CII and familial Alzheimer's disease. When the apolipoprotein CII locus was tested for linkage to familial Alzheimer's disease, LOD scores summed for the complete group of families were negative and close linkage was excluded. Close linkage was also excluded for early‐onset families (mean onset age ≤ 60 years), but small positive LOD scores were obtained for late‐onset kindreds.
Experimental conduction block induced by serum from a patient with anti‐GM1 antibodies
Authors: Santoro Maria , Uncini Antonino , Corbo Massimo , Staugaitis Susan M. , Thomas Florian P. , Hays Arthur P. , Latov Norman
Published: January 2005

Increased titers of antibodies to GM1 ganglioside in humans are associated with lower motor neuron disease and predominantly motor neuropathy with or without conduction block. To investigate the possible mechanism of these antibodies, we injected the serum of a patient with anti‐GM1 antibodies who had motor neuron disease and multifocal motor conduction block, into rat sciatic nerve. When injected with fresh human complement, the serum‐induced conduction block with temporal dispersion and deposits of immunoglobulin were detected at the nodes of Ranvier. Electron microscopic studies revealed demyelination in 6.5% of the fibers. After preabsorbtion with GM1, the serum had no effect, suggesting that the anti‐GM1 antibodies were responsible for the conduction abnormalities.
MELAS: Clinical features, biochemistry, and molecular genetics
Authors: Ciafaloni E. , Ricci E. , Shanske S. , Moraes C. T. , Silvestri G. , Hirano M. , Simonetti S. , Angelini C. , Donati M. A. , Garcia C. , Martinuzzi A. , Mosewich R. , Servidei S. , Zammarchi E. , Bonilla E. , DeVivo D. C. , Rowland L. P. , Schon E. A. , DiMauro S.
Published: January 2005

We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNALeu(UUR) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNALeu(UUR) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.
Wallenberg's syndrome: Lateropulsion, cyclorotation, and subjective visual vertical in thirty‐six patients
Authors: Dieterich Marianne , Brandt Thomas
Published: January 2005

We measured the subjective visual vertical, cyclorotation of the eyes, and head and body lateropulsion in 36 patients with Wallenberg's syndrome. All patients exhibited significant tilts of the internal representation of the gravity vector, as indicated by deviation of subjective visual vertical ipsiversive to the lesion. Most patients (82%) had ipsiversive cyclorotation of one or both eyes, especially excyclotropia of the eye ipsilateral to the brainstem lesion. Twelve of 36 patients (33%), those with the most severe body lateropulsion, had a complete ocular tilt reaction consisting of head tilt, skew deviation, and cyclorotation in the roll plane. We hypothesize that deviation of subjective visual vertical, lateropulsion of the body, and cyclorotation of the eyes are the perceptual, the ocular motor, and the postural consequences of a common lesion of central vestibular pathways that subserve the vestibuloocular reflex in the roll plane. Lateropulsion in patients with Wallenberg's syndrome is interpreted as a postural consequence of an abnormal tilt of the internal representation of orientation in space.
Fabry disease: Immunocytochemical characterization of neuronal involvement
Authors: de Veber Gabrielle A. , Schwarting Gerald A. , Kolodny Edwin H. , Kowall Neil W.
Published: January 2005

Fabry disease is an X‐linked glycosphingolipid storage disease caused by deficiency of α‐galactosidase. Storage of globotriaosylceramide, also known as ceramide trihexoside, is maximal in blood vessels but also occurs in neurons. We performed neuropathological histochemical studies on the brains and spinal cords of 2 patients with confirmed Fabry disease. Luxol fast blue–positive deposits were found in blood vessels throughout the central and peripheral nervous system and within selected neurons in spinal cord and ganglia, brainstem, amygdala, hypothalamus, and entorhinal cortex. Regions adjacent to involved neuronal groups, including nucleus basalis, striatum, globus pallidus, and thalamus, were spared. Electron microscopy showed lamellar cytoplasmic neuronal inclusion bodies. Using a monoclonal antibody reactive with ceramide trihexoside, we found more extensive neuronal deposition than evident by Luxol‐fast blue staining and new areas of neuronal storage in the spinal cord and cerebral cortex. Blood vessels throughout the nervous system were strongly immunoreactive. The highly selective pattern of neuronal involvement we found suggests that glycosphingolipid exposure, uptake, or catabolism varies greatly with respect to neuronal morphology and distribution. The degree of toxicity to neurons and the clinical significance of this neuronal storage remains to be defined.
Preferential loss of striato‐external pallidal projection neurons in presymptomatic Huntington's disease
Authors: Albin Roger L. , Reiner Anton , Anderson Keith D. , Dure Leon S. , Handelin Barbara , Balfour Rosemary , Whetsell William O. , Penney John B. , Young Anne B.
Published: January 2005

We have reported previously that striatal projection neurons are differentially affected in the course of Huntington's disease, and in a prior patient report we noted that differential loss of striatal projection neurons occurs also in patients with presymptomatic Huntington's disease. Striatal neurons projecting to the external segment of the globus pallidus or the substantia nigra show evident loss, whereas those projecting to the internal segment of the globus pallidus appear relatively spared at presymptomatic and early stages of symptomatic Huntington's disease. We now report similar findings in a second apparently presymptomatic Huntington's disease allele carrier.
Suspected low‐grade glioma: Is deferring treatment safe?
Authors: Recht Lawrence D. , Lew Robert , Smith Thomas W.
Published: January 2005

Deferring therapeutic intervention may worsen outcome in patients with low‐grade glioma. To address this issue, we searched our records and located 26 patients who presented with a transient event (most often seizures), who had radiographic evidence strongly suggestive of a low‐grade primary supratentorial neoplasm, and for whom all therapy (except anticonvulsants) was withheld until deemed necessary (WAIT Group). For comparison, 20 patients who presented similarly, but for whom immediate intervention was elected, served as a comparison group (NOWAIT Group). Fifteen patients in the WAIT Group required eventual surgery or radiation therapy at intervals ranging from 4 to 123 months (median, 29 months) between radiographic diagnosis and therapeutic intervention; reasons for such intervention included increasing tumor size, uncontrollable seizures, or malignant transformation of tumor. At surgery, there was an increased number of anaplastic tumors noted in the patients in the WAIT Group (p < 0.02); nevertheless, if the rate of malignant transformation was examined from time of diagnosis, no differences were noted between the patients in the two groups. Similarly, no difference in survival or quality of life could be demonstrated from time of radiographic diagnosis. Therefore, we could not demonstrate that deferring therapy worsens outcome for these patients.
Motor nerve biopsy in severe Guillain‐Barré syndrome
Authors: Hall Susan M. , Hughes Richard A. C. , Atkinson Penny F. , McColl Ian , Gale Andrew
Published: January 2005

We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain‐Barré syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally indentified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain‐Barré syndrome.
Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia
Authors: Mahalingam R. , Wellish M. C. , Dueland A. N. , Cohrs R. J. , Gilden D. H.
Published: January 2005

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV‐1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV‐1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV‐2. These findings indicate the presence of latent HSV‐1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV‐1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV‐1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.
Paresis of contralateral smooth pursuit and normal vestibular smooth eye movements after unilateral brainstem lesions
Authors: Johnston Janine L. , Sharpe James A. , Morrow Mark J.
Published: January 2005

Pursuit and vestibular smooth eye movements were measured in patients with lesions of the caudal brainstem tegmentum identified by magnetic resonance imaging (MRI) and computed tomography (CT), with neuropathological correlation in 1 patient. Contralateral smooth pursuit gain was significantly lower than ipsilateral gain in each patient. Ipsilateral smooth pursuit gain was also subnormal in patients with unilateral pontine damage that caused slowing of ipsilateral saccades. Horizontal vestibulo‐ocular reflex gain and phase were normal. These quantitative correlations indicate that lesions of the pontine tegmentum that paralyze ipsilateral saccades can spare the vestibulo‐ocular reflex, and that smooth pursuit movement and the vestibulo‐ocular reflex can be impaired independently by pontine or medullary lesions. In contrast to lesions at other sites, unilateral lesions of the pontine or medullary tegmentum impair contralateral smooth pursuit more than ipsilateral pursuit movements. These findings provide evidence that a double decussating pathway mediates smooth pursuit; the first decussation is from the pons to the cerebellum, and the second decussation is from the vestibular nucleus to the contralateral abducens nucleus.
Selective culture of mitotically active human Schwann cells from adult sural nerves
Authors: Rutkowski J. Lynn , Tennekoon Gihan I. , McGillicuddy John E.
Published: January 2005

We devised a simple method to isolate mitotically active human Schwann cells from sural nerve biopsy specimens and expand the population in culture. Nerve fascicles were treated with cholera toxin for 7 days in culture before dissociation, which increased the cell yield at least twenty‐five–fold over immediated tissue dissociation. Digesting the tissue completely with enzymes in serum‐containing medium resulted in the highest cell viability, and released 2 to 6 × 104 cells/mg of tissue. Seeding the cells on a poly‐L‐lysine substrate in a small volume of serum‐free medium optimized the plating efficiency. Although Schwann cells comprised 90% of the initial culture population, their numbers declined over time due to a faster mitotic rate of the fibroblasts in the presence of cholera toxin alone. However, treating the cultures with a combination of cholera toxin and forskolin, which act synergistically to elevate cyclic AMP levels, inhibited fibroblast growth without causing Schwann cell toxicity. Adding glial growth factor to the adenyl cyclase activators maximized Schwann cell proliferation, and the population rapidly and selectively expanded. Therefore, it should be possible to generate large numbers of Schwann cells from diseased nerves to study defects in cell function or from normal nerves to study the effects of Schwann cell grafts on neuronal regeneration.
GAP‐43 gene expression is increased in anterior horn cells of amyotrophic lateral sclerosis
Authors: Parhad Irma M. , Oishi Roderick , Clark Arthur W.
Published: January 2005

In amyotrophic lateral sclerosis (ALS), neuronal loss and axonal degeneration occur in motor neurons. Although there is limited axonal regeneration, surviving motor neurons send collateral sprouts to denervated muscle fibers. GAP‐43, a protein enriched in growth cones and synaptic terminals, is thought to have a role in axonal elongation and synaptogenesis. GAP‐43 messenger RNA (mRNA) expression was evaluated in ALS spinal cords using Northern blot analysis and in situ hybridization to assess whether surviving neurons can mount an appropriate response to injury. There was a two‐ to four‐fold increase in GAP‐43 mRNA in ALS that localized to the anterior horn cells. The increase in GAP‐43 mRNA indicates that the mechanism which leads to degeneration in ALS does not compromise the neuron's capacity for vigorous expression of growth‐associated proteins.
Recurrent status epilepticus in children
Authors: Shinnar Shlomo , Maytal Joseph , Krasnoff Lawrence , Moshe Solomon L.
Published: January 2005

Status epilepticus is an uncommon but life‐threatening seizure. Little is known about the risk of recurrent status epilepticus in patients who present with an initial episode. To determine the risk of recurrent status epilepticus in children, we prospectively followed 95 children, identified at the time of their first episode of status epilepticus, for a mean of 29.0 months (range, 4–60 months). The patients' ages ranged from 1 month to 18 years (mean, 4.6 years). The cause of the status epilepticus was classified as idiopathic (n = 24), remote symptomatic (n = 18), febrile (n = 29), acute symptomatic (n = 18), or progressive neurological disorder (n = 6). Sixteen children (17%) had at least 2 episodes of status epilepticus. The risk of recurrent status was 4% (n = 1) in the idiopathic group, 44% (n = 8) in the remote symptomatic group, 3% (n = 1) in the febrile group, 11% (n = 2) in the acute symptomatic group, and 67% (n = 4) in those with progressive neurological disease. Recurrent status epilepticus occurred primarily in neurologically abnormal children. While neurologically abnormal children accounted for 34% (n = 32) of all children with status epilepticus, they comprised 88% (n = 14) of the children with recurrent status epilepticus (p< 0.001) and all 5 of the children with multiple (≥ 3) episodes of status (p< 0.001). Fifteen of 16 children with recurrent status epilepticus were being treated with antiepileptic drugs at the time of recurrence. The morbidity and mortality of status epilepticus were low. No child had a measurable deterioration in neurological function following a subsequent episode of status epilepticus. Recurrent status epilepticus occurs primarily in children with an underlying neurological abnormality. Status epilepticus reoccurs in this group despite conventional antiepileptic drug therapy.
Motion‐defined letter detection and recognition in patients with multiple sclerosis
Authors: Giaschi D. , Regan D. , Kothe A. , Hong X. H. , Sharpe J. A.
Published: January 2005

Two important distinctions in visual perception are (1) between the detection and recognition of shapes (e.g., letters), and (2) between the recognition of shapes defined by a difference in brightness and the recognition of shapes defined by a difference in motion. We report that 6 of 10 patients with multiple sclerosis showed impaired recognition for motion‐defined (Md) letters, although the detection of Md letters was normal as were both detection and recognition of luminance‐defined letters. We have shown that this was not a function of acuity loss or the loss of ability to detect motion or a general failure of recognition per se, but was confined to a loss of ability to recognize Md letters. The neurological implications of these findings are discussed, and it is suggested that the Md letter test be used by others interested in the central pathology of visual disorders.
β‐Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: A regulatory role for cortisol and interleukin‐1
Authors: Zoukos Y. , Leonard J. P. , Thomaides T. , Thompson A. J. , Cuzner M. L.
Published: January 2005

An increased density of β‐adrenergic receptors was demonstrated on peripheral blood mononuclear cells (PMMCs) from patients with progressive or replapsing‐remitting multiple sclerosis (MS). The same observation was made in patients with chronic active rheumatoid arthritis, but not in those with myasthenia gravis. The affinity of the receptors was within the normal range in all tested groups of patients and there was a positive correlation between density and function as determined by intracellular cyclic AMP production after stimulation with isoproterenol. A putative link between inflammatory processes and the functional upregulation of β‐adrenergic receptors on PBMCs was tested by in vitro studies with the soluble mediators interleukin‐1 and hydrocortisone. A functional upregulation of β‐adrenergic receptors was observed when PBMCs from normal control subjects were cultured in the presence of either mediator, whereas the already upregulated receptor density on PBMCs from patients with MS remained unchanged. Whether this represents a recovery mechanism to inflammation in MS or a blunting of homeostatic immunoregulatory mechanisms requires further investigation.
Immunological detection of glutamate receptor subtypes in human central nervous system
Authors: Blackstone Craig D. , Levey Allan I. , Martin Lee J. , Price Donald L. , Huganir Richard L.
Published: January 2005

Glutamate receptors are the principal excitatory neurotransmitter receptors in the central nervous system and are involved in a number of normal and pathological neuronal processes. Using subunit‐specific antipeptide antibodies developed against the predicted amino acid sequences of several rat glutamate receptor cDNAs, we have identified these proteins in post‐mortem human central nervous system tissue. Immunoblotting of dissected brain regions demonstrates that these receptor proteins are differentially distributed. The ability to identify these proteins in post‐mortem human tissues should allow examination of the changes in levels of receptor subtypes that occur in a variety of neurological and psychiatric diseases.
Morphometry, histopathology, and tomography of cerebral atrophy in the acquired immunodeficiency syndrome
Authors: Gelman Benjamin B. , Guinto Faustino C.
Published: January 2005

Patients with the acquired immunodeficiency syndrome (AIDS) commonly display evidence of gross cerebral atrophy, but its true incidence and pathophysiology in the general AIDS population are unknown. In this study, we measured cerebrospinal fluid (CSF) spaces in 64 consecutively autopsied patients with AIDS, compared them with age‐matched non‐AIDS subjects, and correlated them with the microscopic neuropathology at autopsy. Thirty‐seven of the patients with AIDS (58%) had a CSF space index greater than two standard deviations above the mean of the age‐matched control subjects. CSF spaces were expanded the most in frontal and temporal lobes; ventricular spaces were expanded more than sulcal spaces. Regression analysis between age and the measured CSF indexes showed that practically none of the deviation in patients with AIDS could be explained by age‐related atrophy. Patients with atrophy were much more likely to have human immunodeficiency virus type 1–associated histopathological changes in their brains, but the relationships were too weak to establish the microscopic cause of the atrophy. Measurement of CSF spaces in antemortem computed tomographic (CT) scans from 47 of the patients with AIDS revealed the same regional pattern of brain wasting. CT diagnosis of cerebral atrophy was strongly concordant with the postmortem diagnosis, but its severity was diagnosed slightly more conservatively at autopsy. Thus, quantitative analysis of CSF spaces in a robust sampling of patients with AIDS confirms that cerebral atrophy is a sensitive, common, and frequently subtle indication of central nervous system human immunodeficiency virus type 1 infection that may occur independently from any single specific microscopic abnormality. Its presence, severity, and regional pattern are detected with reasonable consistency using CT scanning.
Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke
Authors: del Zoppo Gregory J. , Poeck Klaus , Pessin Michael S. , Wolpert Samuel M. , Furlan Anthony J. , Ferbert Andreas , Alberts Mark J. , Zivin Justin A. , Wechsler Lawrence , Busse Otto , Greenlee Ralph , Brass Lawrence , Mohr J. P. , Feldmann Edward , Hacke Werner , Kase Carlos S. , Biller Jose , Gress Daryl , Otis Shirley M.
Published: January 2005

An open angiography‐based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator(rt‐PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebal hemorrhage were prerequisites for treatment. After the 60‐minute rt‐PA infusion, arterial perfusion was assesed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation, Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 ± 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt‐PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occured in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occured significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.
Magnetoencephalographic localization of epileptic cortex—impact on surgical treatment
Authors: Paetau Ritva , Kajola Matti , Karhu Jari , Nousiainen Unto , Partanen Juhani , Tiihonen Jari , Vapalahti Matti , Hari Riitta
Published: January 2005

A 24‐channel, Planar, superconducting quantum interference device gradiometer, sampling a fourth of the head surface over brain tissue, was used to determine the site of an epileptic focus in a 36‐year‐old woman with intractable complex partial epilepsy. The other presurgical findings appeared divergent: a large arachnoid cyst over the right parietal convexity, dissimilar interictal electroencephalographic patterns, and several neuropsychological dysfunctions. The equivalent current sources of magnetoencephalographic spikes were in the right posterior temporal region of the cortex, 4 cm apart from the cyst. Surgical exploration of the area pinpointed by magnetoencephalography revealed a pachygyric patch of cortex displaying focal discharges on the electrocorticogram. After resection, a dramatic reduction of seizures occurred. The good agreement between electrocorticography and magnetoencephalography warrants future investigation of multichannel magnetoencephalography as a potential alternative to invasive presurgical recordings.
Computer model of ethosuximide's effect on a thalamic neuron
Authors: Lytton William W. , Sejnowski Terrence J.
Published: January 2005

Ethosuximide appears to have a specific effect on the low‐threshold calcium current in thalamic cells. This may be related to its efficacy in the treatment of absence epilepsy. We used a computer model of an individual thalamocortical neuron to better understand the alteration in the low‐threshold calcium current under voltage clamp and to predict response to current injection in the presence of ethosuximide. The full model included nine voltage‐sensitive ionic channels and a realistic dendritic morphology. The model reproduced the two major responses seen in tissue slices: repetitive spiking with depolarization and the low‐threshold calcium spike elicited on release from hyperpolarization. The alteration in low‐threshold calcium current with ethosuximide can be explained by a 10‐mV depolariting shift in the steady‐state activation curve for this channel with a 10% reduction in maximum channel permeability. Simulations of current injection showed that ethosuximide diminished the low‐threshold calcium spike while leaving the tonic firing pattern unaffected. Our results support the hypothesis that ethosuximide's effects on low‐threshold calcium current might selectively alter the dynamics of slow bursting in thalamic cells.
Spectral analysis of the rapid eye movement sleep electroencephalogram in right and left temporal regions: A biological marker of Alzheimer's disease
Authors: Petit Dominique , Montplaisir Jacques , Lorrain Dominique , Gauthier Serge
Published: January 2005

Spectral analysis of electroencephalograms (EEGs) for both wakefulness and rapid eye movement (REM) sleep was performed over the temporal regions in 8 patients with mild to moderate Alzheimer's disease and in 8 age‐matched control subjects. EEG slowing in Alzheimer patients was found to be much more prominent during REM sleep than during wakefulness. In addition, asymmetry on the awake EEG of Alzheimer patients was found to be even more prominent than on the REM sleep EEG. When EEG values of the most impaired hemisphere during REM sleep were examined, no overlap was found between the two groups either for the ratio of slow to fast frequencies or for percent power of each of the frequency bands. This was not the case for the awake EEG. These results suggest that diagnostically meaningful cutoff values for discriminating patients with mild to moderate Alzheimer's disease from age‐matched control subjects can be derived from the REM sleep EEG of the temporal lobe.
Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity
Authors: Jingwu Zhang , Medaer Robert , Hashim George A. , Chin Ying , van den Berg‐Loonen Ella , Raus Jef C. M.
Published: January 2005

A panel of 90 myelin basic protein (MBP)‐specific T‐cell lines were derived from peripheral blood of eight patients with multiple sclerosis and four normal subjects. The precursor frequency of MBP‐reactive T cells in peripheral blood mononuclear cells ranged from 10−7 to 9 × 10−7 (mean, 6.7 × 10−7) in the group of patients with multiple sclerosis and from 0.5 × 10−7 to 9.8 × 10−7 (mean, 5.6 × 10−7) in the control subjects. This difference between the two groups was not statistically significant (p > 0.1). These T‐cell lines expressed exclusively CD3+CD4+CD8‐ phenotypes and were restricted predominantly by HLA‐DR molecules. When tested with fragments and synthetic peptides of human MBP, these MBP‐specific T‐cell lines (45 lines for each group) displayed a limited heterogeneous pattern with a biased recognition to peptide 84‐102 and the C‐terminal peptide 149‐171. The reactivity to the 84‐102 region of MBP was associated with the HLA‐DR2, DRw15 (DRwl5,2) haplotype, whereas the recognition to peptide 149‐171 did not correlate with a particular HLA‐DR allele(s). Furthermore, the majority of T‐cell lines (>75%) were found to exhibit substantial cytotoxic activity against MBP‐coated target cells, but showing no significant difference between these two groups. This MBP‐dependent Cytotoxicity was not associated with epitope specificities of the T‐cell lines tested.
Isolated granulomatous angiitis of the spinal cord
Authors: Caccamo Dario V. , Garcia Julio H. , Ho Khang‐L.
Published: January 2005

We describe a 31‐year‐old diabetic man, with granulomatous angiitis confined to the spinal cord, who developed rapidly progressive spastic paraplegia, clinically interpreted as being secondary to a spinal cord infarct. At the time of autopsy, vasculitis was limited to the spinal cord, without involvement of cerebral vessels. The inflammatory cells were predominantly CD4+ T lymphocytes, with few CD8+ T and B lymphocytes. The phenotypical composition of the inflammatory infiltrate is similar to that described in other granulomatous disorders such as sarcoidosis and tuberculin reaction.
Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations
Authors: DeKosky Dr Steven T. , Harbaugh Robert E. , Schmitt Frederick A. , Bakay Roy A. E. , Chui Helena Chang , Knopman David S. , Reeder Teddi M. , Shetter Andrew G. , Senter Howard J. , Markesbery William R. ,   The Intraventricular Bethanecol Study Group
Published: January 2005

Neurochemical assessments were performed on biopsy samples taken from the right frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the implantation of a ventricular catheter and pump assembly for the infusion of bethanechol chloride as an experimental therapy. The pathologically diagnosed patients with AD (n = 35; mean age, 67 ± 1.5 yr) were compared with a group of samples from normal age‐equivalent autopsied controls (n = 22; mean age, 68 ± 2 yr) and autopsied AD brains (n = 11; mean age, 73 ± 2 yr). Samples were assayed for choline acetyltransferase (ChAT), acetylcholinesterase, binding to {3H}quinuclidinyl benzilate as an index of total muscarinic cholinergic binding, and [3H}pirenzepine binding as an index of Ml cholinergic receptor subtype binding. Mean levels of ChAT activity were decreased in the biopsied patients to 36% of age‐matched autopsied controls. The loss of ChAT activity correlated significantly with the Mini‐Mental State Examination, an index of global cognitive function. Mean ChAT activity in autopsied AD cortex was further decreased compared with controls, indicating continuous decline through the course of the disease. Acetylcholinesterase followed a similar, less dramatic decline. No differences were found in {3H}quinuclidinyl benzilate binding or {3H}pirenzepine binding between biopsied and autopsied controls. Neuritic plaque counts did not correlate with either the Mini‐Mental State Examination or ChAT activity in the biopsy specimens. The correlation of cortical ChAT activity with degree of dementia, although considerably weaker than those of cortical synaptic density with dementia, is the first demonstration of such a relationship in biopsied patients, and suggests another reason why the AD brain may be unresponsive to presynaptic cholinergic manipulations or attempts at enhancement.