bluuebunny/crossref_metadata_2025 huggingface dataset:
Drop attacks with Meniere's syndrome
Authors: Baloh R. W. , Jacobson K. , Winder T.
Published: January 2005

We report the clinical features of 12 patients with drop attacks associated with Meniere's syndrome. Each described a sensation of being pushed, thrown, or knocked to the ground or a sudden illusion of movement of the environment that led to a fall. These episodes were not accompanied by symptoms of their typical attacks of Meniere's syndrome. The drop attacks occurred early and late in the course of the disease; they were the initial manifestation in 1 patient. In the majority the episodes spontaneously remitted, although Meniere's syndrome continued to progress. These attacks probably result from a sudden mechanical deformation of the otolithic membrane of the utricle or saccule due to pressure gradients within the inner ear. They are important to recognize because their prognosis is relatively benign compared to other causes of drop attacks.
Recurrent seizures in children with Shigella‐associated convulsions
Authors: Lahat E. , Katz Y. , Bistritzer T. , Eshel G. , Aladjem M.
Published: January 2005

Fifty‐five children with Shigella‐associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow‐up period was between 6.9 and 14.1 years (9.7 ± 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella‐associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella‐related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions.
Peripheral neuropathy associated with eosinophilia‐myalgia syndrome
Authors: Heiman‐Patterson T. D. , Bird S. J. , Parry G. J. , Varga J. , Shy M. E. , Culligan N. W. , Edelsohn L. , Tatarian G. T. , Heyes M. P. , Garcia C. A. , Tahmoush A. J.
Published: January 2005

In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L‐tryptophan. We evaluated 3 patients with eosinophiliamyalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilatordependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L‐tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L‐tryptophan, its metabolic products, or contaminants within L‐tryptophan preparations.
Adult phosphorylase b kinase deficiency
Authors: Clemens Paula R. , Yamamoto Masahiko , Engel Andrew G.
Published: January 2005

Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.
Effect of digitals on clinical symptoms and conduction variables in patients with multiple sclerosis
Authors: Kaji Ryuji , Happel Leo , Sumner Austin J.
Published: January 2005

Digitalis has been shown to reverse conduction block in demyelinated nerve fibers in experimental animals. In the search for a symptomatic treatment of multiple sclerosis, digoxin (0.02 mg per kilogram of body weight) was given intravenously to 7 patients with probable or clinically definite multiple sclerosis. All of these patients had temperature‐dependent symptoms. In 3 patients, improvement of clinical deficits was observed concurrent with significant changes in evoked potential findings. Digitalis derivatives may be useful in ameliorating symptoms in selected patients with multiple sclerosis.
Noninvasive detection of occlusive disease of the carotid siphon and middle cerebral artery
Authors: Ley‐Pozo Juan , Bernd Ringelstein Erich
Published: January 2005

Recently, transcranial Doppler sonography has been introduced into clinical practice for noninvasive investigation of the large intracranial arteries. To determine its accuracy for detection of stenosing or occluding lesions, 133 consecutive patients were studied by both transcranial Doppler sonography and selective cerebral arteriography. Statistical analysis of findings was done separately for various arterial segments. High values for sensitivity and specificity were found for detecting obstruction of the carotid siphon and main stem of the middle cerebral artery. Diagnostic reliability of transcranial Doppler sonography was also confirmed by the calculation of a chance‐corrected measure of agreement (kappa), which was close to + 1 in all subanalyses. Transcranial Doppler sonography seems to be a valuable tool for noninvasive detection of intracranial lesions of the middle cerebral artery and carotid siphon.
Mild senile dementia of the Alzheimer type: 3. Longitudinal and cross‐sectional assessment
Authors: Berg Leonared , Smith Deborah S. , Morris John C. , Philip Miller J. , Rubin Eugene H. , Storandt Martha , Coben Lawrence A.
Published: January 2005

Sixty‐six subjects diagnosed by validated criteria as having senile dementia of the Alzheimer type (SDAT) were assessed with clinical measures commonly used to study dementia. The severity of the SDAT was mild in 24, moderate in 24, and severe in 18. The data from these three groups in a cross‐sectional study were compared with results in our earlier study of 43 subjects enrolled with mild SDAT and followed longitudinally. We concluded that the cross‐sectional method underestimates the severity of progression as indicated by some of the clinical measures. Additionally, the 24 new subjects with mild SDAT were assessed longitudinally. This replication study confirmed our earlier conclusions that four of six clinical measures showed similar patterns over time and were useful throughout the study, global measures being more informative than brief individual measures with ceiling or floor effects.
Absence of immunoreactive enzyme protewin in short‐chain acylcoenzyme a dehydrogenase deficiency
Authors: Farnsworth L. , Shepherd I. M. , Johnson M. A. , Bindoff L. A. , Turnbull D. M.
Published: January 2005

Defects of short‐chain acylcoenzyme A dehydrogenase (SCAD) may cause a severe metabolic illness in children or a lipid storage myopathy in adults. The childhood form is associated with low enzyme activity, but the synthesis of a normal‐size enzyme protein in cultured skin fibroblasts. We report further biochemical studies on the original patient described with myopathic SCAD deficiency. We show an absence of enzyme protein in skeletal muscle, which both confirms the original diagnosis and suggests that the two forms of SCAD deficiency have a different molecular basis.
The glucose transporter and blood‐brain barrier of human brain tumors
Authors: Guerin Christopher , Laterra John , Hruban Ralph H. , Brem Henry , Drewes Lester R. , Goldstein Gary W.
Published: January 2005

The glucose transporter of the human brain has been localized to endothelial cells expressing the blood‐brain barrier, but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability. We investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques. Vessels in 9 of 10 low‐grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter. Glioblastoma vessels were transporter‐positive in only 2 of 10 specimens. Vessels in all three metastatic tumors were negative for the glucose transporter. The decrease in transporter expression observed in higher‐grade tumors occurred independently of increases in vascular permeability. In low‐grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related, but vessels in 6 of 9 anaplastic astrocytomas were transporter‐positive despite contrast enhancement. These findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood‐brain barrier. They also have potential implications for the therapy and prognosis of astroglial neoplasms.
Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa
Authors: Packer Roger J.
Published: January 2005

Chemotherapy has only marginal efficacy in adult malignant brain tumors. In contrast, drug therapy is considerably more effective in medulloblastoma/primitive neuroectodermal tumors (MB/PNET) of the posterior fossa, the most common childhood primary central nervous system tumor. At the time of disease recurrence, a variety of different single agents and drug combinations result in tumor shrinkage and increased survival. The addition of chemotherapy to standard radiotherapy improves the rate and length of disease‐free survival for those children with MB/PNET who have the most extensive tumors at diagnosis. It remains to be determined which drug or drug combinations are the most effective in MB/PNET, and which patients are most likely to benefit from chemotherapy. Chemotherapy may be useful to reduce or, in selected cases, obviate the need for radiotherapy and reduce treatment‐related sequelae.
Elevated alpha–tumor necrosis factor levels in spinal fluid from HIV‐1–infected patients with central nervous system involvement
Authors: Grimaldi L. M. E. , Martino G. V. , Franciotta D. M. , Brustia R. , Castagna A. , Pristerà R. , Lazzarin A.
Published: January 2005

To assess the role of alpha–tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha–tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C‐1 (20) of the Centers of Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha–tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p < 0.05) and 22 of 30 cerebrospinal fluid (p < 0.0002) samples from clinically more advanced patients (group IV B and group IV C‐1). Alpha–tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C‐1 patients. In 15 of 19 (79%) patients with human immunodeficiency virus type 1 encephalopathy (group IV B, 9 of 10 patients) and with opportunistic infections of the central nervous system (groupIV C‐1, 6 of 9 patients), alpha–tumor necrosis factor levels were more elevated in cerebrospinal fluid (mean value, 42 pg/ml) than in serum (mean value,20.7 pg/ml), whereas the opposite (p < 0.002) was found in 6 of 7 (86%) patients with systemic opportunistic infections not involving the central nervous system (serum mean value, 38.9 pg/ml vs. cerebrospinal fluid mean value, 15.0 pg/ml). No correlation was found between elevated alpha–tumor necrosis factor levels and clinical evidence of dementia or central nervous system demyelination. We conclude that intrathecal production of alpha–tumor necrosis factor occurs during central nervous system localization of human immunodeficiency virus type 1 infection. Alpha–tumor necrosis factor elevation seems to be related to active infection/inflammation. Measurement of cerebrospinal fluid alpha–tumor necrosis factor levels may thus represent a useful marker for ongoing central nervous system localization of human immunodeficiency virus type 1 infection.
Neuroanatomy of fragile X syndrome: The posterior fossa
Authors: Reiss Allan L. , Aylward Elizabeth , Freund Lisa S. , Joshi Paramjit K. , Bryan R. Nick
Published: January 2005

The occurrence and specificity of posterior fossa abnormalities as measured from magnetic resonance images of the brain were investigated in a group of 14 males with fragile X syndrome and comparison groups consisting of 17 males with other causes of developmental disability and 18 males with normal IQs. The size of the posterior cerebellar vermis was significantly decreased and the fourth ventricle significantly increased in the group of males with fragile X syndrome compared with males in both comparison groups. These neuroanatomical abnormalities appeared to be secondary to hypoplasia rather than atrophy.
Local cerebral glucose utilization in rats with petit mal–like seizures
Authors: Nehlig Astrid , Vergnes Marguerite , Marescaux Christian , Boyet Sylvette , Lannes Beatrice
Published: January 2005

The quantitative 2‐[14C]deoxyglucose autoradiographic method was applied to the measurement of local cerebral metabolic rates for glucose in a model of genetic petit mal–like seizures in a strain of Wistar rats. During the experimental period, epileptic rats exhibited synchronous spike‐and‐wave discharges recorded from the cerebral cortex, whereas the electroencephalographic pattern of control animals was normal. An overall consistent increase in local cerebral metabolic rates for glucose was observed in epileptic rats as compared to nonepileptic control rats. This increase was statistically significant in 52 of the 59 cerebral structures studied and concerned all cerebral functional systems. These results are in accordance with positron emission tomography measurements in humans with typical childhood absence epilepsy. There is a lack of anatomical correlation between areas demonstrating hypermetabolism and areas where spike‐and‐wave discharges are recorded. Thus, the diffuse increase in cerebral energy metabolism in epileptic rats as compared to controls is not directly related to the occurrence of spike and wave discharges.
Tests of EEG localization accuracy using implanted sources in the human brain
Authors: Cuffin B. Neil , Cohen David , Yunokuchi Kazutomo , Maniewski Roman , Purcell Christopher , Cosgrove G. Rees , Ives John , Kennedy John , Schomer Donald
Published: January 2005

The accuracy with which electrical sources in the brain can be localized by using electroencephalograms measured on the scalp is not well known. In this study, tests of localization accuracy were performed by using implanted dipolar sources in the human brain. These dipoles are created by passing a weak (subthreshold) current through intracerebral electrodes implanted in the brains of epileptic patients for seizure monitoring. The locations of these dipoles are accurately known from roentgenographs. First, 16 electroencephalograms produced by these dipoles were recorded, then inverse solutions were calculated for the apparent sources of these electroencephalograms. Finally, the locations of the apparent sources were compared with the known locations of the implanted dipoles to determine localization error. The average localization error for a total of 28 dipoles in 3 subjects was 1.1 cm. These results indicate that good localization accuracy for focal sources in the brain can be provided by scalp electroencephalograms.
Cortical dysplasia in temporal lobe epilepsy: Magnetic resonance imaging correlations
Authors: Kuzniecky Ruben , Garcia Julio H. , Faught Edward , Morawetz Richard B.
Published: January 2005

Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical‐white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy.
Adult polyglucosan body disease: The diagnostic value of axilla skin biopsy
Authors: Busard H. L. S. M. , Gabreëls‐Festen A. A. W. M. , Renier W. O. , Gabreëls F. J. M. , Joosten E. M. G. , van't Hof M. A. , Rensing J. B. M.
Published: January 2005

The diagnostic value of axilla skin biopsy has been investigated in a patient with adult polyglucosan body disease. The biopsy data have been compared with those of control subjects and with those from previously reported patients with Lafora's disease. In a patient with adult polyglucosan body disease and in patients with Lafora's disease, an abundance of polyglucosan bodies was found in the myoepithelial cells of the axillary apocrine glands. In the control group of subjects, polyglucosan bodies were only sporadically seen. Axilla skin biopsy is, therefore, an easy and reliable method for confirming the diagnosis of adult polyglucosan body disease.
Cranial neuropathy associated with primary amyloidosis
Authors: Traynor Ann E. , Gertz Morie A. , Kyle Robert A.
Published: January 2005

We report 6 patients for whom cranial neuropathy was a major manifestation of primary amyloidosis. In 3 of the 6, multiple cranial nerves were involved. All had tissue biopsy documentation of amyloidosis. In 2, nerve biopsy also confirmed amyloidosis. All had renal involvement manifested by proteinuria. Primary systemic amyloidosis must be considered in the differential diagnosis of cranial neuropathy, especially when proteinuria is present.
Acetylcholine receptor—specific T‐Lymphocyte clones in the normal human immune repertoire: Target epitopes, hla restriction, and membrane phenotypes
Authors: Salvetti Marco , Jung Stefan , Chang Shau‐Feng , Will Hans , Schalke Berthold C. G. , Wekerle Hartmut
Published: January 2005

Potentially autoimmune T‐lymphocyte lines specific for the nicotinic acetylcholine receptor of the neuromuscular junction have been isolated previously from patients with myasthenia gravis. We report on the isolation and expansion of T cells specific for the acetylcholine receptor of Torpedo californica or for a recombinant mammalian acetylcholine receptor alpha chain peptide (X4), from the peripheral blood of 11 healthy donors. Two major T‐cell epitopes, located between amino acid positions 44‐104 and 141‐172, were identified using a panel of overlapping mammalian alpha chain fusion proteins. Most T lines recognized the acetylcholine receptor epitopes in the molecular context of HLA‐DR molecules. Unexpectedly, all the T. californica acetylcholine receptor‐specific T lines obtained from one DR4 (DRw53), DQw3 donor and two DR4, w8 (DRw53), DQw3 donors were restricted by DRw53 product(s). Using DR gene‐transfected L cells as antigen presenters, in 4 lines, a close relationship between the recognized epitope and the restricting DR element was revealed. The membrane phenotype of the T. californica acetylcholine receptor‐and X4‐specific T lines was predominantly CD4+CD8−, with some CD4+CD8+ components. It did not significantly differ from that of control, tuberculin purified protein derivate‐specific T lines raised from the same donors. These findings are in harmony with previous ones demonstrating the presence of potentially autoimmune T‐lymphocyte clones within normal immune repertoires.
Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease
Authors: Olanow C. W. , Gauger L. L. , Cedarbaum J. M.
Published: January 2005

We studied the pharmacokinetics of levodopa and its metabolites in plasma and ventricular cerebrospinal fluid in 4 parkinsonian patients with indwelling Ommaya reservoirs placed at the time of previous adrenalmedullary to caudate nucleus transplantation. Cerebrospinal fluid levodopa levels were 11.9% of those in plasma. Motor performance and dyskinesia correlated more closely with the time course of the appearance of levodopa in the ventricular cerebrospinal fluid than with the plasma levodopa concentration and did not correlate with plasma 3‐O‐methyldopa or cerebrospinal fluid 3‐O‐methyldopa or homovanillic acid. Our data confirm that the wearing off of the levodopa effect in patients with advanced Parkinson's disease is a function of drug concentration in the central nervous system.
Deletion of mitochondrial DNA in patients with combined features of kearns‐sayre and MELAS syndromes
Authors: Zupanc Mary L. , Moraes Carlos T. , Shanske Sara , Langman Craig B. , Ciafaloni Emma , DiMauro Salvatore
Published: January 2005

A 9‐year‐old girl and an 11‐year‐old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged‐red fibers and Southern analysis demonstrated a distinct heteropolasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) generecently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS). These 2 children had combined features of Kearns‐Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression.
Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis: A positron emission tomographic study
Authors: Brooks D. J. , Ibanez V. , Playford E. D. , Sawle G. V. , Leigh P. N. , Kocen R. S. , Harding A. E. , Marchsden C. D.
Published: January 2005

Using [18F]dopa, [11C]raclopride, C15O2, and positron emission tomography, we have assessed striatal dopamine storage capacity, dopamine D2‐receptor integrity, and regional cerebral blood flow, respectively, of 6 patients with neuroacanthocytosis. The patients with neuroacanthocytosis all had chorea and variable combinations of seizures, dementia, axonal neuropathy, and orolingual self‐mutilation. [18F]dopa positron emission tomographic findings were compared with 30 normal controls and 16 patients with sporadic, L‐dopa‐responsive, Parkinson's disease. Caudate and anterior putamen [18F]dopa uptake were normal in patients with neuroacanthocytosis, but mean posterior putamen [18F]dopa uptake was reduced to 42% of normal, similar to that in patients with Parkinson's disease. In patients with neuroacanthocytosis, mean equilibrium caudate: cerebellum and putamen: cerebellum [11C]raclopride uptake ratios were reduced to 54% and 62% of normal, compatible with a 65% and 53% loss of caudate and putamen D2‐receptor‐binding sites, respectively. Striatal and frontal blood flow was also depressed. The severe loss of D2‐receptor‐bearing striatal neurons, with concomitant loss of dopaminergic projections from the nigra to the posterior putamen, is consistent with both chorea and extrapyramidal rigidity being features of patients with neuroacanthocytosis.
Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic parkinson's disease
Authors: Goto Satoshi , Hirano Asao
Published: January 2005

The parabrachial nucleus is believed to play a role in autonomic regulation. We have used the Fontana‐Masson ammoniacal silver nitrate method and a tyrosine hydroxylase–immunostaining technique to demonstrate the presence of neuromelanin‐containing catecholaminergic neurons in the parabrachial nucleus of normal individuals. In addition, we also show that there is a significant reduction of these catecholaminergic neurons and presence of Lewy bodies in the parabrachial nucleus of patients with idiopathic Parkinson's disease. These findings may be related to the several autonomic disturbances that may occur in idiopathic Parkinson's disease.
Comparison of bitemporal and unitemporal epilepsy defined by depth electroencephalography
Authors: Hirsch Lawrence J. , Spencer Susan S. , Williamson Peter D. , Spencer Dennis D. , Mattson Richard H.
Published: January 2005

Of 166 consecutive patients studied with depth electroencephalography (EEG), 87 had seizures arising from one temporal lobe and 23 had seizures arising independently from each temporal lobe. We retrospectively reviewed and compared those patients with unitemporal and those with bitemporal seizures. There were no statistically significant differences between the two groups in terms of age at onset of seizures, duration of epilepsy, localization of scalp EEG abnormalities, surgical results, or pathological findings. The bitemporal group, however, had significantly fewer patients with a history of febrile seizures (p $$ 0.025). Two patients with bitemporal seizures were later found to have extratemporal lesions, and one an extrahippocampal temporal lesion, on magnetic resonance scans; one patient's extratemporal lesion was resected and all habitual seizures stopped. These findings suggest that a single pathophysiological process accounts for unitemporal and some bitemporal epilepsy, but that independent onset of seizures from each temporal lobe detected by depth EEG may also indicate extratemporal foci.
Temporal lobectomy in patients with bitemporal epilepsy defined by depth electroencephalography
Authors: Hirsch Lawrence J. , Spencer Susan S. , Spencer Dennis D. , Williamson Peter D. , Mattson Richard H.
Published: January 2005

Patient selection for temporal lobectomy was reviewed for 23 patients with seizures that arose independently from each temporal lobe as detected by depth electroencephalography (EEG). Although neuropsychological testing, interictal EEG findings, imaging studies, and subclinical seizures were also considered, all patients offered temporal lobectomy had (1) at least 50% of the clinical seizures originating from the lobe to be resected, (2) adequate contralateral memory on testing with amobarbital, and (3) no clear evidence of an extratemporal focus. Eleven patients underwent temporal lobectomy. Pathological findings were considered positive in all nine specimens reviewed. Nine patients had no seizures, one had greater than 75% reduction in seizure frequency, and 1 had 50 to 75% reduction. Pathological features and clinical outcome were similar in the 6 patients with fewer than 80% and the 5 patients with at least 80% of seizures originating from the resected lobe. Thus, having fewer than 80% of seizures originate from one temporal lobe should not be an absolute contraindication for temporal lobectomy.
Postictal language assessment and lateralization of complex partial seizures
Authors: Privitera Michael D. , Morris George L. , Gilliam Frank
Published: January 2005

We performed a prospective study of ictal and postictal language function after 105 temporal lobe complex partial seizures in 26 patients. Seizure localization was verified by a greater than 90% reduction in seizure frequency after temporal lobectomy. At the time of the seizure, the patient was asked to read a test phrase aloud until it was read correctly and clearly. In all 62 seizures originating from the left temporal lobe, the patient took more than 68 seconds to read the test phrase correctly (mean, 321.9 seconds); in 42 of 43 seizures from the right temporal lobe, the patient read the test phrase in less than 54 seconds (mean, 19.7 seconds). Postictal paraphasias occurred in 46 of 62 seizures from the left temporal lobe (11 of 14 patients). In this study, quantifying the time delay in reading a test phrase lateralized seizure onset in all 26 patients tested, proving significantly more accurate than any other single noninvasive presurgical test.
Focal neuronal migration disorders and intractable partial epilepsy: Results of surgical treatment
Authors: Palmini André , Andermann Frederick , Olivier André , Tampieri Donatella , Robitaille Yvon
Published: January 2005

Twenty‐six patients with focal or lateralized neuronal migration disorders and intractable partial epilepsy were treated surgically. Twenty‐four had reliable follow‐up ranging from 1 to 15 years (mean, 5.0). Pathologically, they fell into two categories: focal cortical dysplasia (12 patients) and forme fruste of tuberous sclerosis (8 patients). In the remaining 4 patients, the material was inadequate for histological analysis. Outcome regarding seizure control was assessed according to a classification most sensitive to variations in frequency of major attacks. Ten (42°) of the 24 patients achieved good or excellent outcome, 6(25°) had a worthwhile decrease in seizure frequency, and 8 (33°) had only discrete improvement. The variable most strongly correlated with surgical outcome was the amount of lesion removed. Seventy‐seven percent of patients in whom a complete excision or excision of 50° or more of the lesion was accomplished achieved excellent or good surgical outcome. Conversely, no patient with less than 50° of the lesion removed attained the same result. There was no correlation between other clinical, radiological, or electrographic variables and outcome regarding seizure control. Specifically there was no significant correlation between the amount of excision of the epileptogenic area as judged by scalp electroencephalography and electrocorticography studies, and surgical outcome. In patients with neuronal migration disorders and intractable partial epilepsy, removal of the structural abnormality takes precedence over removal of epileptogenic tissue as the main surgical strategy to achieve seizure control.
Excitotoxicity in the embryonic chick spinal cord
Authors: Stewart Gregory R. , Olney John W. , Pathikonda Maya , Snider William D.
Published: January 2005

Recent evidence implicates excitatory amino acids (EAAs), acting as excitotoxic agents, in the pathogenesis of neurological disorders involving the spinal cord. In this study, we used the chick embryo spinal cord as an vitro model for studying the sensitivity of spinal neurons to the excitotoxic effects of EAA agonists. Compounds tested include the prototypic receptor‐specific agonists, N‐methyl‐D‐aspartate (NMDA), quisqualic acid (Quis), and Kainic acid (KA), and the plant‐derived excitotoxic food poisons, β‐N‐oxalylamino‐L‐alanine, β‐N‐menthylamino‐L‐alanine, and domoic acid. Each agonist induced concentration‐dependent acute degeneration of neurons distributed throughout the spinal cord. These cytopathological changes consisted of acute edematous degeneration of dendrosomal structures in the dorsal horn and intermediate zone, and dark cell changes with intracytoplasmic vacuolization of motor neurons; this damage is identical to that induced by excitotoxin agonists in other regions of the central nervous system. The NMDA receptor‐specific antagonist MK‐801 completely blocked toxicity of NMDA, and the nonNMDA antagonist CNQX preferentially blocked the toxicity of Quis‐ and KA‐type agonists in the spinal cord. Our findings suggest that (1) the majority of spinal neurons have all three subtypes of EAA receptors, making them acutely vulnerable to excitotoxin exposure; and (2) EAA antagonists are effective in preventing excitotoxin‐induced damage of the spinal cord.
Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease
Authors: Harris Gordon J. , Pearlson Godfrey D. , Peyser Carol E. , Aylward Elizabeth H. , Roberts Joy , Barta Patrick E. , Chase Gary A. , Folstein Susan E.
Published: January 2005

The characteristic pathological features of Huntington's disease (HD) are neostriatal atrophy and neuronal loss. Although neuroradiological studies often show caudate atrophy in patients with moderate HD, frequently no caudate atrophy is found early in the illness. There have been no quantitative reports to date on in vivo putamen volume measures in mild HD, although the structure is known to be neuropathologically involved in the illness. We measured volumes of caudate nucleus and putamen and bicaudate ratios (BCR) from magnetic resonance images, blind to diagnosis, in 15 patients with mild HD and 19 age‐ and sex‐matched control subjects using a computerized image analysis system. The region showing greatest atrophy was the putamen, which was reduced 50.1% in mean volume in HD patients compared with control subjects (p<0.000001). In contrast, caudate volume was reduced 27.7% (p = 0.004). BCR was increased 28.5% in HD patients (p = 0.0002). Discriminant function analysis was 94% effective in identifying the diagnostic group based on putamen volume alone, whereas caudate measures had considerable overlap. Correction of putamen volume for head size led to 100% separation by group. Putamen measures and BCR correlated with neurological examination scores but caudate volume did not. Volumetric measurement of putamen is a more sensitive indicator of brain abnormalities in mild HD than measures of caudate atrophy.
Nerve growth factor prevents experimental cisplatin neuropathy
Authors: Apfel Stuart C. , Arezzo Joseph C. , Lipson Leeanne , Kessler John A.
Published: January 2005

Cisplatin is a widely used antitumor agent, the dose‐limiting toxicity of which is predominantly large‐fiber sensory neuropathy. Prevention of such a neuropathy would extend the usefulness of this agent, allowing higher doses and longer periods of treatment. We report here that we have successfully established cisplatin neuropathy in mice measured by using behavioral, biochemical, and electrophysiological techniques, and that subcutaneous administration of human recombinant nerve growth factor (NGF) prevents or delays the neuropathy. Cisplatin administration reduced sensory ganglion levels of the peptide transmitter, calcitonin gene–related peptide, slowed nerve conduction in the tail and impaired proprioception as measured by the ability to balance on a rotating dowel. NGF coadministration appeared to prevent all these abnormalities. Treatment of the human toxic neuropathy with its well‐established time of onset, simple clinical course, and the accessibility of nerve to NGF administered systemically may provide the best clinical setting for the first human trials of NGF.
Proton magnetic resonance spectroscopic imaging for metabolic characterization of demyelinating plaques
Authors: Arnold Douglas L. , Matthews Paul M. , Francis Gordon S. , O'Connor John , Antel Jack P.
Published: January 2005

We used proton magnetic resonance (MR) spectroscopic imaging to determine the serial changes in MR signals from choline, creatine, lactate, and N‐acetylaspartate in and around a large demyelinating lesion followed over a period of 8 months. Elevated lactate and choline signals were observed at the first examination 3 days after the onset of symptoms. Reduced N‐acetylaspartate signals were observed a few days afterward. The abnormals metabolite signals varied in different regions of the lesions and extended beyound the borders of abnormal signal intensity seen on conventional MR imaging (MRI). On the last examination at 8 months when the lesion appeared much smaller on MRI, choline signals from the center of the lesions were still high, but were falling. Choline signals outside the lesions on MRI had returned to normal as had lactate signals everywhere. Importantly, there was no recovery of N‐acetylasparatate signals in or adjaccent to the lesion on MRI. This serial study demonstrates the potential of MR spectroscopic imaging for characterizing the chemical pathological evolution of demyelinating lesions in ways that conventional MRI cannot. We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N‐acetylaspartate can provide an index of irreversible damage in the nervous system.
In vivo imaging of glucose consumption and lactate concentration in human gliomas
Authors: Herholz K. , Heindel W. , Luyten P. R. , denHollander J. A. , Pietrzyk U. , Voges J. , Kugel H. , Friedmann G. , Heiss W.‐D.
Published: January 2005

Twenty patients with histologically confirmed gliomas were studied with positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H‐MRS). PET with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) provided tomograms of the metabolic rate of glucose. MRS images were obtained by combining volume‐selective excitation with phase‐encoded acquisition. With 32 × 32 gradient phase‐encoding steps, an in‐plane resolution of 7 × 7 mm was achieved. From this set of spectra, lactate maps were created and compared with PET maps of glucose metabolism. Maximum glucose metabolic rates within tumors (relative to metabolic rates of glucose in contralateral regions of the brain) were correlated significantly with maximum lactate concentrations (relative to N‐acetyl aspartate peaks in the contralateral part of the brain). In 8 tumors, no lactate was detected, and in 7 of these the maximum glucose metabolic rate was below the median value. The tumor with the highest lactate concentration also had the highest glucose metabolic rate. The topographic relation between glucose metabolic rate and lactate concentration could be analyzed in 9 patients by three‐dimensional alignment of the PET and MRS images. In that analysis, maximum lactate concentrations were often not found in the same location as maximum glucose metabolism, but lactate tended to accumulate in tumor cysts, necrotic areas, and the vicinity of the lateral ventricles. The combination of FDG PET and 1H‐MRS imaging demonstrates details of the spatial relation between the two poles of nonoxidative glycolysis, glucose uptake and lactate deposition. Both methods can be used as diagnostic tools to study an abnormality of energy metabolism that may be an indicator of dedifferentiation and malignancy.
Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy
Authors: Tornatore Carlo , Berger Joseph R. , Houff Sidney A. , Curfman Blanche , Meyers Karen , Winfield David , Major Eugene O.
Published: January 2005

Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central vervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circula‐tion. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy–proven PML for the JCV genome. Two non‐PML control groups, consisting of 26 patients seropositive for human immunodeficiency virus type 1 (HIV‐1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was exmimined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV‐1–seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD‐1 strain of JCV in one patient with PML, a MAD‐4 strain in a second patient with PML, and a slightly modified MAD‐4 strain in an HIV‐1–positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system. We also identified the JCV genome in the lymphocytes of a group of HIV‐1–seropositive patients with no clinical evidence of PML, suggesting that they may be at risk for development of PML and can be identified in a presymptomatic state.
Functional reorganization of the brain in recovery from striatocapsular infarction in man
Authors: Weiller Cornelius , Chollet François , Friston Karl J. , Wise Richard J. S. , Frackowiak Richard S. J.
Published: January 2005

We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex.
Idiopathic childhood stroke is associated with human leukocyte antigen (HLA)–B51
Authors: Mintz Mark , Epstein Leon G. , Koenigsberger M. Richard
Published: January 2005

We report four children with idiopathic stroke syndromes who were assayed for human leukocyte antigen (HLA) class I markers and found to have HLA‐B51 in common. This finding suggests that may be a genetic predisposition for “idiopathic” childhood stroke, and host factors, possibly in concert with environmental factors or viruses, may play a major role in the mechanism of unexplained occlusion of the cerebral vasculature in children.
Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis–dutch type share a decrease in cerebrospinal fluid levels of amyloid β‐protein precursor
Authors: van Nostrand William E. , Wagner Steven L. , Haan Joost , Bakker Egbert , Roos Raymund A. C.
Published: January 2005

The amyloid β‐protein is a 39‐42 amino acid peptide that is deposited in senile plaques and in cerebral vessel walls in individuals with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHW A‐D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid β ‐protein precursor. Here we show that individuals with the HCHWA‐D mutation and clinically manifesting the disease have markedly decreased cerebrospinal fluid levels of soluble amyloid β‐protein precursor (0.7 ± 0.4 μg/ml) compared with age‐matched normal subjects (3.0 ± 0.2 μg/ml) as determined by quantitative immunoblotting and enzyme‐linked immunosorbent assays. Similarly, age‐matched patients diagnosed with probable Alzheimer's disease also have decreased cerebrospinal fluid levels of soluble amyloid β‐protein precursor (1.0 ± 0.3 μg/ml). These parallel findings suggest a common biochemical marker for these two diseases and further establish the pathogenic relatedness of HCHWA‐D and Alzheimer's disease.
Spectrum of human immunodeficiency virus–associated neocortical damage
Authors: Masliah Eliezer , Achim Cristian L. , Ge Nianfeng , DeTeresa Richard , Terry Robert D. , Wiley Clayton A.
Published: January 2005

A spectrum of neurocognitive defects, termed human immunodeficiency virus type 1 (HIV‐1)–associated cognitive/motor complex, has been described in patients with acquired immunodeficiency syndrome (AIDS). AIDS dementia complex (ADC) is a severe form of this disease seen in 20 to 30% of terminally ill patients. The etiology of this complex is distinct from commonly observed opportunistic infections seen in brains of patients with AIDS and has been attributed to HIV infection within the brain. At autopsy, the brains of patients with ADC contain numerous HIV‐infected macrophages/microglia with prominent subcortical damage, together termed HIV encephalitis. We retrospectively analyzed all 107 brains from a three‐year period (1988–1990) of AIDS autopsies using immunocytochemistry to detect HIV. Rather than breaking into distinct groups of HIV encephalitis versus non‐HIV encephalitis, the specimens revealed a spectrum of severity of HIV infection. Although only 16% of the brains showed the histological hallmarks of HIV encephalitis, more than 50% of the autopsies showed moderate to severe HIV infection. In a subset of 23 AIDS autopsies during which short postmortem times and absence of significant opportunistic infection permitted quantitative analysis of dendritic and synaptic complexities, we identified a strong correlation between neocortical dendritic and presynaptic damage and abundance of HIV envelope protein in the neocortical gray and deep white matter. This correlation suggests that the presence of HIV‐1 in the neocortex may be responsible by direct or indirect mechanisms for dendritic and synaptic damage.
Facilitation of responses to motor cortex stimulation: Effects of isometric voluntary contraction
Authors: De Noordhout A. Maertens , Pepin J. L. , Gerard P. , Delwaide P. J.
Published: January 2005

In 7 normal subjects we compared the facilitatory effect of isometric contraction of the tibialis anterior on the size of electromyographic responses evoked in this muscle by electric stimuli applied over the cervical column and by electric and magnetic percutaneous stimulation of the motor cortex. No significant difference was found between the degrees of facilitation of the responses to any of the stimuli. Using collision techniques, we also showed that the pyramidal fibers activated by spinal and cortical stimuli are the same. Facilitation induced by isometric contraction (20% maximum) was of similar or greater magnitude than that found with constant vibration of the tendon of the target muscle. In cases where vibration and contraction had equal facilitatory effects, there was no further facilitation of the responses when both conditions were applied together. These findings indicate that the facilitatory effect of isometric contraction of the target muscle essentially originates at a spinal level rather than in the motor cortex.