bluuebunny/crossref_metadata_2025 huggingface dataset:
Microtubular reorganization and dendritic growth response in alzheimer's disease
Authors: McKee Ann C. , Kowall Neil W. , Kosik Kenneth S.
Published: January 2005

Cytoskeletal disruption is a key pathological feature of Alzheimer's disease (AD). We used refined immunocytochemical techniques to define the range of abnormalities affecting the microtubule system in AD hippocampus. Minimal tau and tubulin immunoreactivity was granular and accumulated in otherwise normal neuronal perikarya. As tau‐reactive neurofibrillary tangles formed, granular tau and tubulin staining diminished, and ubiquitin reactivity developed. In regions of high neurofibrillary tangle density, microtubule‐associated protein 2 (MAP2) histochemical features of remaining nontangled neurons included apical dendritic degeneration with proliferation of basal dendrites. In addition to perisomatic dendritic proliferation, there was massive sprouting of tau‐immunoreactive distal dystrophic neurites. Sprouting proximal dendrites and dystrophic neurites often demonstrated growth‐cone‐like lamellipodia and filopodia. Degeneration of the perisomatic proliferating dendrites was characterized by the accumulation of fibrillar tau immunoreactivity. The colocalization of MAP2 and tau in growth structures recapitulated their codistribution in developing neurites. The data suggest that extensive plasticity and growth response occur in tandem with neuronal degeneration in AD, and that reorganization of the cytoskeletal microtubule system may underlie these proliferative changes.
Mitochondrial myopathies: Clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DNA
Authors: Holt I. J. , Harding A. E. , Cooper J. M. , Schapira A. H. V. , Toscano A. , Clark J. B. , Morgan‐Hughes J. A.
Published: January 2005

Analysis of mitochondrial DNA (mtDNA) in muscle and blood from 72 patients with mitochondrial myopathy showed that 30 had major deletions of a variable proportion of muscle mtDNA. All of these 30 patients presented with progressive external ophthalmoplegia and limb weakness, and 8 had the additional features of the Kearns‐Sayre syndrome. Of the 42 patients without detectable muscle mtDNA deletions, 10 had progressive external ophthalmoplegia and limb weakness, 2 had the Kearns‐Sayre syndrome, 11 had limb weakness without extraocular involvement and 19 had multisystem disorders predominantly affecting the central nervous system. Only 2 patients with mtDNA deletions had clinically affected relatives, compared with 10 of those without deletions. In the 4 patients with polarographic defects exclusively involving complex I (NADH coenzyme Q reductase), the deleted protein‐coding genes were confined to those for complex I subunits. Thirteen other patients with apparently identical deletions had variable clinical and biochemical features. Immunoblots of complex I polypeptides from patients with deletions were either indistinguishable from controls or showed only a mild generalized decrease in all identifiable subunits.
Pyruvate dehydrogenase complex deficiency: Biochemical and immunoblot analysis of cultured skin fibroblasts
Authors: Old Susan E. , de Vivo Darryl C.
Published: January 2005

Cultured skin fibroblasts were obtained from 11 children with lactic acidemia and neurological disturbances. The residual activities of pyruvate dehydrogenase complex were 9 to 45% of control values in all specimens. Immunoblot analysis of mitochondrial proteins using polyclonal antibodies against the alpha and beta subunits of the first component (E1) of the pyruvate dehydrogenase complex revealed markedly decreased amounts of cross‐reacting material in 4 boys who died in infancy. Two of the boys were half brothers related through a common mother. A fifth boy had an alteration of the electrophoretic mobility of the E1α subunit and normal E1β subunit abundance. The remaining 6 patients (2 boys and 4 girls) had normal findings on Western blot assay, and all 11 patients had normal E2 and E3 patterns. These findings suggest that the E1α subunit gene represents a genetically vulnerable site on the X chromosome. Decreased abundance of E1 components appears to be associated with death in infancy. A normal Western blot analysis is compatible with long‐term survival despite decreased catalytic activity of the pyruvate dehydrogenase complex.
Partial seizures with visual disturbance treated by radiotherapy of cavernous hemangioma
Authors: Lance James W. , Smee Robert I.
Published: January 2005

A man aged 26 years had been subject to frequent transient episodes of left homonymous hemianopia, initially accompanied by visual hallucinations and left miosis, since the age of 8 years. These partial seizures recurred 3 to 30 times each month in spite of treatment with anticonvulsant medication. The causative lesion, which had escaped detection by cerebral angiography and repeated computed tomographic scanning, was shown by magnetic resonance imaging to be a small cavernous hemangioma in the right occipital lobe. This was treated by a course of fine‐beam radiotherapy directed to the lesion. After treatment the partial attacks ceased, although one nocturnal clonic seizure occurred 12 months after radiotherapy and 6 weeks after stopping all anticonvulsant medication.
Gm haplotypes in inflammatory demyelinating polyneuropathies
Authors: Feeney D. J. , Pollard J. D. , McLeod J. G. , Stewart G. J. , De Lange G. G.
Published: January 2005

The possible association of Gm haplotypes with inflammatory neuropathies has been studied in 59 patients with Guillain‐Barré syndrome and 55 patients with chronic inflammatory demyelinating polyradiculo‐neuropathy. The frequency of Gm haplotype 1,2,17;21 (or z,a,x;g) was significantly raised in the patients with Guillain‐Barré syndrome. These findings provide further evidence for an association of chromosome 14 genes with inflammatory neuropathies.
Neurophysiology of fastest voluntary muscle contraction in hereditary neuropathy
Authors: Logigian Eric L. , Hefter Harald H. , Reiners Karlheinz , Freund Hans‐Joachim
Published: January 2005

In patients with hereditary motor and sensory neuropathy types I (demyelinative) and II (neuronal) and in normal subjects isomatic force and electromyographic activity of the first dorsal interosseous muscle were recorded during fastest voluntary contractions and during twitches evoked by nerve stimulation. The maximum voluntary force of the first dorsal interosseous muscle was also measured. In patients, fastest voluntary contraction time (i.e., time from ooset of contraction to peak force) was prolonged and inversely proportional to maximum voluntary force. Maximum rate of rise of tension (i.e., slope of rise in force) was reduced and directly proportional to maximum voluntary force. In patients with hereditary motor and sensory neuropathy type I, contraction time was longer and the maximum rate of rise of tension was lower than in those with hereditary motor and sensory neuropathy type II. In patients and normal subjects, voluntary contraction time was closely correlated with the duration of electromyographic bursts. In patients, the twitch contraction time was prolonged and inversely proportional to maximum voluntary force. Twitch contraction amplitude was diminished and directly proportional to maximum voluntary force. Neither twitch contraction time nor amplitude were dependent on the type of hereditary motor and sensory neuropathy. Twitch contraction time evoked by proximal nerve stimulation was minimally longer than that evoked by distal stimulation. In fastest voluntary muscle contraction performed by patients with hereditary motor and sensory neuropathy, it is argued that: (1) Decrease in maximum rate of rise of tension is due to a reduced number of motor units, an increase in motor unit contraction time, and possibly lower motor unit firing rates in type I compared to type II neuropathy patients. (2) The central nervous system appears to adapt to a decreased rate of rise of tension by prolonging duration of the agonist electromyographic burst, thus lengthening contraction time. This may result in the higher peak forces than if burst duration were normal.
Immunoglobulins promote remyelination in the central nervous system
Authors: Rodriguez Moses , Lennon Vanda A
Published: January 2005

Remyelination of central nervous system axons was promoted by systemic injection of serum immunoglobulin G (IgG) from donor mice hyperimmunized with homogenized spinal cord. In SJL/J mice infected with Theiler's virus, primary demyelination and inflammation in the spinal cord were extensive. Following treatment with IgG to spinal cord homogenate, new myelin synthesis as measured by quantitative morphometry increased sixfold. Cells in areas of remyelination that incorporated [3H]thymidine did not express differentiation markers of macrophages, oligodendrocytes, or astrocytes but were identified by electron microscopic autoradiography as progenitor glial cells. These findings raise the possibility that IgG secreted in demyelination lesions might have the protential to promote myelin repair.
Effects of seizures on learning, memory, and behavior in the genetically epilespy‐prone rat
Authors: Holmes Gregory L. , Thompson James L. , Marchi Teresa A. , Gabriel Pamela S. , Hogan Martha A. , Carl Frank G. , Feldman Daniel S.
Published: January 2005

To determine whether frequent seizures can cause deficits in learning and behavior, immature genetically epilepsyprone rats (GEPRs) were subjected to 66 audiogenic stimulations (Group 1). GEPR littermates were handled and placed in the sound chamber but were not stimulated (Group 2). Group 3 comprised genetically epilepsy‐resistant rats (GERRs) who received audiogenic stimulations but had no seizures. After 3 weeks of stimulations the rats were tested for learning, memory, and behavior using the T‐maze, water maze, open field activity test, home cage intruder test, and handling test. When compared with the control GEPRs and GERRs, Group 1 rats reached criteria less frequently in the T‐maze, required longer times to find the platform in the water maze, and were active in the open field activity test, less aggressive in the home cage intruder test, and more irritable and aggressive in the handling test. This study demonstrates that frequent, brief seizures in immature animals result in significant detrimental changes in learning, memory activity level, and behavior.
Activation of the epileptic focus by transcranial magnetic stimulation of the human brain
Authors: Hufnagel A. , Elger C. E. , Durwen H. F. , Böker D. K. , Entzian W.
Published: January 2005

To establish whether transcranial magnetic stimulation is able to activate the primary epileptic focus preferntially, 13 patients who had medically intractable complex partial seizures were examined prior to surgical therapy. Single or a series of magnetic stmuli were applied to various regions of the skull. The effects of transcranial magnetic stimulation were monitored via subdurally implanted electrodes. In the process of presurgical evaluation, the dosage of anticonvulsant medication had been reduced in all patient but one. Transcranial magnetic stimulation was able to activate the epileptic focus (or foci) in 12 of the 13 patients. Distinct patterns of focal activation were observed in 3 patients who had several foci. No epileptiform potentials were induced outside epileptic foci, which had been identified by corticographic recordings. In one patient a complex partial seizure that was induced was identical to her habitual seizures. In another patient, a complete transition from a nonactive theta focus to a self‐sustained epileptic focus occurred. A facilitation of epileptiform afterdischarge was seen with sequential stimulation. No adverse effects were either reported by the patients or observed by the investigators. In summary transcranial magnetic stimulation is able to activate the epileptic focus (or foci) and consequently may be an additional tool for the localization of epileptic foci in presurgical evaluation.
Opioid and nonopioid mechanisms may contribute to dynorphin's pathophysiological actions in spinal cord injury
Authors: Faden Alan I.
Published: January 2005

It has been suggested that the opioid dynorphin, an endogenous agonist for k‐opiate receptors, contributes to secondary tissue damage after spinal cord injury. To evaluate this hypothesis further, effects of intrathecally administered dynorphin (Dyn) A‐(1‐17), dynorphin antiserum, or the k‐selective opiate antagonist nor‐binaltorphimine (nor‐BNI) were studied in rats subjected to standardized impact trauma to the thoracic spinal cord. Effects of intrathecal Dyn A‐(1–17) were also compared to those of Dyn A‐(2–17), which is inactive at opiate receptors, in uninjured and injured animals. Both Dyn A‐(1–17) and Dyn A‐(2‐17) produced motor dysfunction in uninjured rats, but Dyn A‐(1–17) was approximately 2.5 times more potent. At lower doses of Dyn A‐(1–17), paraparesis was markedly attenuated by nor BNI; nor‐BNI was less effective at higher doses of Dyn A‐(1–17) and did not modify the motor dysfunction produced by Dyn A‐(2–17). Treatment with dynorphin antiserum significantly improved outcome after trauma as compared to control treatment with normal rabbit serum or leucine‐enkephalin antiserum. Dyn A‐(1–17), but not Dyn A‐(2–17) at similar doses, exacerbated neurological dysfunction after spinal cord injury. Pretreatment with nor‐BNI attenuated neurological dysfunction after traumatic spinal cord injury to a similar degree in rats administered saline or Dyn A‐(1–17). These observations support the hypothesis that dynorphin contributes to certain pathophysiological changes after traumatic spinal cord injury through both opiate‐receptor (k‐receptor)–mediated and nonopioid mechanisms.
Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945–1984
Authors: Katusic Slavica , Beard C. Mary , Bergstralth Erik , Kurland Leonard T.
Published: January 2005

The overall crude incidence rate of trigeminal neuralgia per 100,000 population in Rochester, Minnesota, for 1945 through 1984 was 4.3 for both sexes combined. The age‐adjusted (to total 1980 US population) rate for women (5.9) was significantly higher than that for men (3.4). Annual incidence rates increased significantly with age in both women and men. Data based on evidence in the medical records suggest that trigeminal neuralgia is a rather rare and unpredictable disease: The number of episodes varies from 1 to 11, and length of episode from 1 day to 4 years. This study indicates an elevated relative risk associated with hypertension (both overall and among women in the cohort). Also, prevalence of multiple sclerosis was significantly greater among the group of 75 patients who had trigeminal neuralgia. Since the data on treatment in this study do not correspond to a randomized clinical trial, they are presented as empirical results only and show no single treatment of choice for trigeminal neuralgia.
Immunological studies in tropical spastic paraparesis
Authors: Jacobson Steven , Gupta Ajay , Mattson David , Mingioli Elizabeth , McFarlin Dale E.
Published: January 2005

Tropical spastic paraparesis (TSP) and other chronic‐progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T‐lymphotropic virus type I (HTLV‐I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA‐DR and interleukin‐2–receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus–specific cytotoxic T‐cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T‐cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV‐I–like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus.
Age‐related changes in the human nigrostriatal dopaminergic system
Authors: De Keyser Jacques , Ebinger Guy , Vauquelin Georges
Published: January 2005

A deficiency of dopamine in the striatum may contribute to the decline in motor function associated with aging. We examined the effect of aging on the densities of the D1 and D2 dopamine receptors, their high‐agonist affinity sites, and the dopamine uptake sites in postmortem human putamen (n = 32; age range, 19–88 years). With aging a steady decrease was seen in dopamine uptake sites (p < 0.001), confirming previous morphometric and biochemical data of an age‐related loss of nigrostriatal axons. In contrast, the concentrations of the D1 and D2 dopamine receptors and their high‐agonist affinity sites, which are believed to represent the functionally active receptors, were not affected by the aging process. These results may have implications for the pharmacological treatment of the age‐related decline in motor function.
Degeneration of spinocerebellar neurons in amyotrophic lateral sclerosis
Authors: Williams Celia , Kozlowski Mark A. , Hinton David R. , Miller Carol A.
Published: January 2005

The selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord. In normal control subjects, monoclonal antibody 6A2 showed specificity for neurons of the dorsal nucleus of Clarke, the cells of origin of the dorsal spinocerebellar tract. Immunoreactive neurons were also observed in locations corresponding to the central cervical nucleus and spinal border region, containing neurons of the cervicospinocerebellar and ventral spinocerebellar tracts, respectively. The latter two neuronal subsets are indistinguishable from surrounding neurons when conventional histological stains are used. Antigen 6A2 was distributed on surfaces of neuronal somas and proximal neurites and extended into the extracellular space. A second antibody, monoclonal antibody 44.1, labeled the cytoplasm of neuronal somas and neurites, including all monoclonal antibody 6A2‐reactive cells and alpha motoneurons. In spinal cords of all 5 patients with amyotrophic lateral sclerosis, monoclonal antibody 6A2 reactivity in the majority of spinocerebellar neurons was absent or localized to the somal cytoplasm, which still stained with monoclonal antibody 44.1. In more severely involved tissues, there was loss of some spinocerebellar neurons and a corresponding loss of monoclonal antibody 44.1 reactivity. These findings confirm involvement of the spinal cord components of the spinocerebellar system at all levels in sporadic amyotrophic lateral sclerosis and suggest that some surface molecules are modified during the degenerative process.
DNA length polymorphism 5′ to the myelin basic protein gene is associated with multiple sclerosis
Authors: Boylan Kevin B. , Takahashi Naoki , Paty Donald W. , Sadovnick Adele D. , Diamond Marc , Hood Leroy E. , Prusiner Stanley B.
Published: January 2005

A site of DNA polymorphism linked to the myelin basic protein gene, identified as restriction fragment length polymorphism, was analyzed in a population‐based study comparing patients with clinically definite multiple sclerosis (MS) and population‐matched control subjects. A 0.9‐kilobase (kb) genomic DNA fragment (EcoG) encompassing the first exon of the human myelin basic protein gene, located on the long arm of chromosome 18, identified ten alleles arising from a region of DNA, 1.5 kb 5′ to the myelin basic protein gene first exon coding region. Produced by RsaI digests and ranging in length from 2.05 to 2.15 kb, these alleles vary in size by up to 100 base pairs due to insertion or deletion, or both, from a 1‐kb length of repetitive DNA. Allele frequencies among 65 patients with MS were compared with those of 63 control subjects. Chi square for these data was significant (p<0.001), largely due to a preponderance in the patients with MS of alleles in the 2.14‐ to 2.15‐kb range. Comparison of the numbers of patients with MS and control subjects bearing specific alleles showed that 45% of the patients carried at least one allele of 2.14 to 2.15 kb as opposed to 19% of control subjects (p<0.005). These data, while preliminary, suggest that patients with MS differ from population‐matched control subjects with respect to DNA polymorphism linked to the myelin basic protein gene. Although no pathogenic relationship between this polymorphism and MS can be presupposed, this finding raises the possibility that the myelin basic protein gene or some other myelin basic protein‐linked locus may be a factor in susceptibility to MS.
Microvascular changes in early and advanced dermatomyositis: A quantitative study
Authors: Emslie‐Smith Alison M. , Engel Andrew G.
Published: January 2005

In adult dermatomyositis 10 muscle specimens with no or minimal histological alterations were compared with 7 that showed typical alterations. Five specimens from patients with inclusion body myositis, 5 from patients with polymyositis, and 8 from normal subjects served as controls. Vascular endothelium, visualized with the lectin Ulex europaeus agglutinin I, and complement membrane attack complex were demonstrated in the same cryostat sections by paired immunofluorescence. Large randomly selected fields were analyzed to determine the number of capillaries per square millimeter of fiber area (capillary density), per 1,000‐m̈m2 area of each muscle fiber (capillary index), and in 100 × 100m̈m grid squares. In dermatomyositis specimens with minimal structural alterations there was focal capillary depletion, the capillary density was significantly reduced, and the frequency distributions of the capillary index and grid count were shifted to the left. In advanced dermatomyositis specimens, the findings were similar but more severe. In both kinds of specimens, clusters of capillaries reacted for complement membrane attack complex. The 2 patients with the highest proportion of vessels positive for membrane attack complex had a fulminant and fatal course. In polymyositis and inclusion body myositis specimens, the capillaries had a normal overall density and none reacted for membrane attack complex. The findings imply that the capillaries are an early and specific target of the disease process in dermatomyositis.
Striatal and nigral neuron subpopulations in rigid Huntington's disease: Implications for the functional anatomy of chorea and rigidity‐akinesia
Authors: Albin Roger L. , Reiner Anton , Anderson Keith D. , Penney John B. , Young Anne B.
Published: January 2005

Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity‐akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid‐akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid‐akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid‐akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase–immunoreactive (TH‐IR) neurons in the substantia nigra. In rigid‐akinetic HD brains, there was no obvious reduction of nigral TH‐IR neurons, indicating that rigid‐akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid‐akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid‐akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.
The prevalence of dementia and Alzheimer's disease in Shanghai, China: Impact of age, gender, and education
Authors: Zhang Mingyuan , Katzman Robert , Salmon David , Jin Hua , Cai Guojun , Wang Zhengyu , Qu Guangya , Grant Igor , Yu Elena , Levy Paul , Klauber Melville R. , Liu William T.
Published: January 2005

We report the prevalence rates for dementia and Alzheimer's disease (AD) obtained from a probability sample survey of 5,055 noninstitutionalized older persons in Shanghai, China. A two‐stage procedure was used for case finding and case identification. A Chinese version of the Mini‐Mental State Examination was used to determine cases of possible dementia. Three different cutoff points on this mental status test were used depending on the respondent's level of education. Clinical evaluations, based on functional assessments and psychiatric inverview, medical and neurological examinations, three standardized mental status tests, and a selected group of psychometric tests, were made in the second stage of the study to ascertain the clinical diagnoses of dementia and AD utilizing the Diagnostic and Statistical Manual for Mental Disorders, edition 3 and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, respectively. The prevalence rate of dementia in persons 65 years and older was 4.6%. Clinically diagnosed AD accounted for 65% of the subjects with dementia. These findings indicate that the prevalence of dementia in Shanghai is very much higher than figures published earlier for China and Japan, and at the lower part of the range of values reported for community residents in the United States and other Western countries, but less than half of that reported in the recently published survey of the elderly in East Boston. Increasing age, gender (female), and low education are each highly significant and independent risk factors for dementia. One hypothesis to explain the increased prevalence in elderly women who had received no formal education invokes the possibility of an effect of early deprivation, perhaps lowering brain %reserve,% allowing the symptoms of dementia to appear at an earlier date during disease progression.
Normocalcemic tetany abolished by calcium infusion
Authors: Day John West , Parry Gareth J.
Published: January 2005

Tetany is a disorder of increased neuronal excitability usually associated with hypocalcemia. We studied a patient with typical tetanic cramps that responded to intravenous infusion of calcium despite normal serum concentrations of total and ionized calcium. Three generations were affected by similar symptoms, suggesting that this is a dominantly inherited disorder of neuronal hyperirritability.
Intracranial hypertension associated with unruptured cerebral arteriovenous malformations
Authors: Chimowitz Marc I. , Little John R. , Awad Issam A. , Sila Cathy A. , Kosmorsky G. , Furlan Anthony J.
Published: January 2005

Only 6 patients with intracranial hypertension associated with unruptured cerebral arteriovenous malformations have been reported. We report 6 additional patients seen at the Cleveland Clinic during the past 10 years. The average age was 28 years (range, 19–44 years); 4 were women. Symptoms and signs included papilledema (6 patients), headache (6), transient nonepileptic focal symptoms (4), visual obscurations (3), ipsilateral carotid or ocular bruits (3), abnormal visual fields (3), focal seizures (2), and progressive visual loss (1). Enhanced computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated the malformations in all 6 patients. The malformations were large, supplied by the branches of the middle and anterior cerebral arteries, with the posterior cerebral artery contributing in 3 patients, and all drained into the superior sagittal sinus. Associated venous obstruction was seen in 2 patients. Four patients underwent excision of the arteriovenous malformation, with resolution of papilledema in all 4. Measurements of cortical arterial and venous pressures during surgery in 3 patients showed decreased feeding artery pressures and elevated draining vein pressures, which normalized after removal of the malformation. Treatment in the 2 remaining patients consisted of medical therapy (acetazolamide, furosemide, steroids) alone in 1 patient, and in conjunction with proton beam radiation in the other. Papilledema resolved in the former patient, but the patient receiving proton beam radiation still had papilledema 2 years later. Intracranial hypertension associated with unruptured cerebral arteriovenous malformations occurs in young patients with high flow malformations that drain into the superior sagittal sinus, and is likely the result of increased cortical venous and superior sagittal sinus pressure. Excision of the malformation effectively reduces the intracranial pressure.
Mechanism of muscle wasting in myotonic dystrophy
Authors: Griggs Robert C. , Jozefowicz Ralph , Kingston William , Nair K. Sreekumaran , Herr Barbara E. , Halliday David
Published: January 2005

Myotonic dystrophy is associated with progressive muscular atrophy. In order to determine the mechanism of muscle wasting in this condition, we measured fractional mixed skeletal muscle protein synthesis in the postabsorptive state in 8 patients with myotonic dystrophy, and compared the results with those of 10 normal subjects. Fractional muscle protein synthesis was determined by measuring the increment of 13C leucine in mixed skeletal muscle protein obtained by needle biopsy from the quadriceps muscle during a primed‐continuous infusion of L‐(1‐13C) leucine. We used plasma 13C α‐ketoisocaproate (representing intracellular leucine labeling) as the precursor pool for the calculation of fractional muscle protein synthesis and leucine kinetics. Fractional muscle protein synthesis was depressed in the patients with myotonic dystrophy (28% decrease, p < 0.02). Leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux were not different between the patients with myotonic dystrophy and the normal control subjects. Muscle atrophy in myotonic dystrophy reflects a selective decrease in muscle protein synthesis without any similar decrease in nonmuscle protein synthesis. This decrease may result from an impaired end‐organ response to anabolic hormones or substrates.
Antibody response to rubella virus structural proteins in multiple sclerosis
Authors: Nath Avindra , Wolinsky Jerry S.
Published: January 2005

The antibody response to the structural proteins of rubella virus was studied in patients with multiple sclerosis (MS). Irrespective of the antibody titer to whole rubella virus, the relative proportion of the IgG response to the surface glycoprotein E1 was diminished, and that to the surface glycoprotein E2 was elevated in MS patients when compared to a matched control population of normal healthy individuals or a group of patients with systemic lupus erythematosus and other collagen vascular diseases. No difference was observed in the response to the core protein of rubella virus on comparing the MS and normal control groups. This divergence in the relative antibody response to the viral surface proteins suggests that the vigorous antibody response to rubella virus reported in MS is not simply an expression of a nonspecific polyvalent B‐cell response.
Detection of the anti‐Hu antibody in the serum of patients with small cell lung cancer—A quantitative western blot analysis
Authors: Dalmau Josep , Furneaux Henry M. , Gralla Richard J. , Kris Mark G. , Posner Jerome B.
Published: January 2005

We looked for the presence of the anti‐Hu antibody in the sera from 50 normal subjects; 44 patients with small cell lung cancer, not associated with paraneoplastic disease; and 25 patients with small cell lung cancer associated with paraneoplastic sensory neuropathy, encephalomyelitis, or both. Using the avidin‐biotin immunoperoxidase method and a highly sensitive quantitative Western blot analysis, the anti‐Hu antibody was not detected in the 50 normal human sera. Seven of the 44 patients with small cell lung cancer but no paraneoplastic syndrome had detectable levels (average titer, 76 U/ml) of anti‐Hu antibody on Western blot. These levels are significantly lower than the average titer of the 25 patients who had small cell lung cancer and paraneoplastic sensory neuropathy or encephalomyelitis (average titer, 4,592 U/ml). In the group with nonparaneoplastic small cell lung cancer (low anti‐Hu titer) there was a predominance of women (5 women: 2 men), and all patients had “limited” disease when diagnosed. In the antibody‐negative group the sex ratio was 16 women to 21 men and 51% of the patients had “extensive” disease. None of the 7 patients with a low‐titer anti‐Hu antibody developed a paraneoplastic syndrome by the time of writing. The anti‐Hu antibody appears, when present, to be a good marker for small cell lung cancer and, when present at high titer, for small cell lung cancer associated with a paraneoplastic syndrome.
Increase in differentiated type of T lineage cells in the myasthenic thymus: Two‐color fluorocytometric analysis
Authors: Fujii Naoki , Itoyama Yasuto , Goto Ikuo
Published: January 2005

We made use of two‐color flow cytometry to examine thymic lymphoid cells from patients with myasthenia gravis. The CD4+CD8− cells and the CD4−CD8+ cells were significantly increased in the thymus from the patients, compared with findings in the control samples. Conversely, the CD4+CD8+ cells were significantly decreased, Significant increases in CD1−CD3+ cells and significant decreases in CD1+CD3− cells were noted. The percentage of CD45R+ cells also increased. There were no increases in activated T lymphocytes, defined as CD4+DR+ cells, CD8+DR+ cells, or IL2R+ cells. We conclude that the proportion of T lineage lymphocytes that are differentiated is increased in the thymus of patients with myasthenia gravis, and could reflect accelerated differentiation.
Increased ratio of quinolinic acid to kynurenic acid in cerebrospinal fluid of D retrovirus—infected rhesus macaques: Relationship to clinical and viral status
Authors: Heyes Melvyn P. , Mefford Ivan N. , Quearry Bonnie J. , Dedhia Manish , Lackner Andrew
Published: January 2005

Increased concentrations of excitotoxin quinolinic acid in cerebrospinal fluid (CSF) are associated with infection with the human immunodeficiency virus (HIV‐1) and have been implicated in the pathogenesis of the acquired immune deficiency syndrome (AIDS) dementia complex. In the present study, inoculation of macaques with D/1/California, an immunosuppressive serotype 1 type D retrovirus, was associated with acute and chronic increases in CSF and serum quinolinic acid concentrations in macaques that had developed SAIDS, a simian disease analogous to AIDS in humans–particularly macaques with demonstrable opportunistic infections. Kynurenic acid, an antagonist of excitatory amino acid receptors as well as the excitotoxic effects of quinolinic acid, was also increased in the CSF of SAIDS macaques, but to a significantly lesser degree than was quinolinic acid (kynurenic acid, 1.8‐fold; quinolinic acid, 15.6‐fold). CSF quinolinic acid, but not kynurenic acid, was also increased in viremic macaques with SAIDS‐related complex (2.4‐fold) and asymptomatic virus positive carriers (3.4‐fold). Macaques that had recovered from D/1/California infection and were antibody positive and virus negative had normal CSF quinolinic acid and kynurenic acid concentrations. Increased activity of indoleamine‐2,3‐dioxygenase, the first enzyme of the kynurenine pathway, was indicated in the macaques with SAIDS by reduced serum L‐tryptophan and elevated serum L‐kynurenine concentrations. Macaques infected with D/1/California may provide a primate model for investigation of the mechanisms involved in increases in CSF quinolinic acid in retrovirus and other infectious diseases, including HIV‐1. It remains to be determined whether the increased CSF quinolinic acid concentrations and the increased ratio of quinolinic acid to kynurenic acid have neurological significance or are a useful “marker” of infection.
Cerebrospinal fluid choline levels are decreased in Parkinson's disease
Authors: Manyam Bala V. , Giacobini Ezio , Colliver Jerry A.
Published: January 2005

We examined acetylcholinesterase (AChE) activity and choline levels in cerebrospinal fluid (CSF) in 16 patients with idiopathic Parkinson's disease and 9 control subjects of corresponding age: 8 were untreated Parkinson's patients; 4 were treated with carbidopa‐levodopa (100/1,000 mg/day) for 20 ± 3 months; and 4 were treated with carbidopa‐levodopa (110/1,100 mg/day) for 28 ± 18 months plus amantadine (220 mg/day) for 16 ± 8 months. CSF choline levels (nmol/ml) were 2.97 ± 0.79 (control subjects); 1.31 ± 0.29 (untreated patients); 1.00 ± 0.29 (carbidopa‐levodopa treated); and 1.26 ± 0.19 (carbidopa‐levodopa/amantadine treated). Choline levels were significantly lower in untreated and treated patients compared to control subjects (p = 0.0001). AChE activity did not differ in Parkinson's disease patients as compared to control subjects. The reduced level of choline in CSF may reflect a deficit in choline transport into the brain or a decrease of choline‐phospholipid output from the brain.
Amyotrophic lateral sclerosis: Amino acid levels in plasma and cerebrospinal fluid
Authors: Perry Thomas L. , Krieger Charles , Hansen Shirley , Eisen Andrew
Published: January 2005

Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patiends with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients. Autopsy studies have shown glutamate contents to be significantly decreased in brain and spinal cord in ALS. These observations suggested that a systemic abnormality of glutamate metabolism might underlie the pathogenesis of ALS. We report here the findings of our studies of amino acid concentrations in patients with the sporadic form of ALS. Glutamate concentrations were normal in the fasting plasma of a great majority of the patients with ALS. Concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined. b̃‐N‐Methylamino‐L‐alanine, a plant neurotoxin possibly responsible for causing the Guamanian form of ALS, was not detectable in the plasma or CSF of any of our patients. Our findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids.
Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis
Authors: Rothstein Jeffrey D. , Tsai Guochuan , Kuncl Ralph W. , Clawson Lora , Cornblath David R. , Drachman Daniel B. , Pestronk Alan , Stauch Barbara L. , Coyle Joseph T.
Published: January 2005

Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p > 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N‐acetyl‐aspartyl glutamate and its metabolite, N‐acetyl‐aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N‐acetyl‐‐aspartyl glutamate and N‐acetyl‐aspartate was decreased by 60% (p > 0.05) and 40% (p > 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.
The role of plasmapheresis in childhood guillain‐barré syndrome
Authors: Epstein Mark A. , Sladky John T.
Published: January 2005

Plasmapheresis has been advocated in the treatment of childhood Guillain‐Barré syndrome under the assumption that the results of adult series can be extrapolated to children. To test this assumption, we retrospectively evaluated the medical charts of all children who were admitted to The Children's Hospital of Philadelphia between January 1984 and March 1989, with the diagnosis of Guillain‐Barré syndrome. Of the 30 patients identified, 7 were excluded because they had mild disease. Of the remaining 23, 9 underwent plasmapheresis and 14 served as historic control subjects. The two groups were similar with respect to age, presenting symptoms, finding on initial physical examination, and antecedent illnesses at the time of diagnosis. The mean time to recover to Grade 2 (independent ambulation) was significantly shorter in the plasmapheresis‐treated group, 24.0 ± 25.4 days, compared to 60.2 ± 43.6 days in control subjects (mean ± 1 SD). Our results indicate that plasmapheresis diminishes morbidity in childhood Guillain‐Barré syndrome by shortening the interval until recovery of independent ambulation.
Middle cerebral artery strokes causing homonymous hemianopia: Positron emission tomography
Authors: Kiyosawa Motohiro , Bosley Thomas M. , Kushner Michael , Jamieson Dara , Alavi Abass , Reivich Martin
Published: January 2005

Eight patients were evaluated with 18F‐fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuroimaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p < 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%;p < 0.01) and lateral occipital cortex (35%;p < 0.05).
Motor neuron disease in a patient with a monoclonal IgMk directed against GM1, GD1b, and high‐molecular‐weight neural‐specific glycoproteins
Authors: Nobile‐Orazio E. , Legname G. , Daverio R. , Carpo M. , Giuliani A. , Sonnino S. , Scarlato G.
Published: January 2005

In a patient with motor neuron disease and benign IgMk monoclonal gammopathy, the M rprotein reacted with the glycolipids GM1, GD1b, and asialo GM1 and, by immunoblot, with some high‐molecular‐weight neural‐specific glycoproteins. The main reactive bands had an approximate molecular weight of 250 and 400 kd, were most concentrated in the spinal cord, and were also bound by the lectin peanut agglutinin. The presence of the Gal(b̃1‐3) GalNAc epitope on these neural‐specific glycoproteins may help to explain the selective neurological impairment of the patient.
Auras and subclinical seizures: Characteristics and prognostic significance
Authors: Sperling Michael R. , O'Connor Michael J.
Published: January 2005

The characteristics and prognostic significance of subclinical seizures and independent auras were studied in 40 patients with partial epilepsy who had long‐term electroencephalographic (EEG) monitoring with intracranial electrodes. Focal, restricted subclincal seizures were noted in 23 patients, and 11 patients experienced auras that were accompanied by ictal EEG discharges. Auras and subclinical seizures usually were identical in EEG appearance, but were distributed differently among patients. The subclinical seizures and auras usually had the same origin as complex partial seizures, but did not always reliably indicate complex partial seizure origin. Subclinical seizures and auras were of favorable prognostic significance for patients undergoing temporal lobectomy. A majority (>80%) of individuals with subclinical seizures and auras were free of complex partial seizures after surgery, whereas a minority (29%) of patients without subclinical seizures and auras became free of complex parital seizures.
Increased MEPP frequency as an early sign of experimental immune‐mediated motoneuron disease
Authors: García Jesús , Engelhardt Jozsef I. , Appel Stanley H. , Stefani Enrico
Published: January 2005

Intracellular recordings of miniature end‐plate potentials were performed in extensor digitorum longus muscles from guinea pigs with experimental immune‐mediated motoneuron destruction. In the early stages of the disease, the miniature end‐plate potential frequency was elevated compared to that in control and normal animals. The amplitude and time course of the miniature end‐plate potentials as well as the resting potential of the muscle fibers were not altered, which implies integrity of the postjunctional membrane. The increase in frequency of miniature end‐plate potential reflects an increase of basal acetylcholine release and documents dysfunction of the presynaptic terminal of the neuromuscular junction. The increased frequency was associated with high levels of antimotoneuronal IgG in the blood and the presence of IgG at motor end‐plates. These data suggest that the presynaptic terminal of the neuromuscular junction may be involved in the immune attack in animal models of motoneuron degeneration.
Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis
Authors: Lampson Lois A. , Kushner Pinky D. , Sobel Raymond A.
Published: January 2005

Monoclonal antibody immunocytochemsitry was used to examine spinal cord and muscle in amyotrophic lateral sclerosis for changes that would indicate ongoing or potential immune activity. Increased expression of class I and II major histocompatibility complex (MHC) antigens was seen in the affected areas of spinal cord. New MHC expression was concentrated in phagocytes, particularly in degenerating white matter in which they were dispersed in the tissue and also packed around blood vessels. MHC antigen was not revealed in motor neurons or skeletal muscle fibers. An anti‐pan–T‐cell monoclonal revealed small numbers of T cells in degenerating white matter. Similar changes have been seen in other neurodegenerative disorders. They suggest a potential for (secondary) cell‐mediated activity in the affected areas rather than an ongoing MHC‐restricted T‐Cell response. Vessel‐associated phagocytes may be a source of antigen to peripheral lymphoid tissue, stimulating production of the autoantibodies that have been described.