bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging in isolated noncompressive spinal cord syndromes
Authors: Miller D. H. , McDonald W. I. , Blumhardt L. D. , du Boulay G. H. , Halliday A. M. , Johnson G. , Kendall B. E. , Kingsley D. P. E. , MacManus D. G. , Moseley I. F. , Rudge P. , Sandercock P. A. G.
Published: January 2005

The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan. In chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory‐supported, definite multiple sclerosis as was the case in 28 patients in this series.
Kynurenate inhibition of cell excitation decreases stroke size and deficits
Authors: Germano Isabelle M. , Pitts Lawrence H. , Meldrum Brian S. , Bartkowski Henry M. , Simon Roger P.
Published: January 2005

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.
Transient global amnesia: The electroencephalogram at onset
Authors: Cole Andrew J. , Gloor Pierre , Kaplan Reed
Published: January 2005

A middle‐aged man experienced onset of transient global amnesia while undergoing an electroencephalogram. No important change in electroencephalographic activity occurred. This case provides evidence against the hypothesis that epileptic discharge is responsible for transient global amnesia.
Axonal transport in neurological disease
Authors: Griffin John W. , Watson Danny F.
Published: January 2005

The axonal transport systems have a wide variety of primary roles and secondary responses in neurological disease processes. Recent advances in understanding these roles have built on the increasingly detailed insights into the cell biology of the axon and its supporting cells. Fast transport is a microtubule‐based system of bidirectional movement of membranous organelles; the mechanism of translocation of these organelles involves novel proteins, including the recently described protein of fast anterograde transport, kinesin. Slow transport conveys the major cytoskeletal elements, microtubules, and neurofilaments. Several types of structural changes in diseased nerve fibers are understood in terms of underlying transport abnormalities. Altered slow transport of neurofilaments produces changes in axonal caliber (swelling or atrophy) and is involved in some types of perikaryal neurofibrillary abnormality. Secondary changes in slow axonal transport—for example, the reordered synthesis and delivery of cytoskeletal proteins after axotomy—also can produce changes in axonal caliber. Secondary demyelination can be a prominent late consequence of a sustained alteration of neurofilament transport. Impaired fast transport is found in experimental models of distal axonal degeneration (dying back). Retrograde axonal transport provides access to the central nervous system for agents such as polio virus and tetanus toxin, as well as access for known and hypothetical trophic factors. Correlative studies of axonal transport, axonal morphometry, cytoskeletal ultrastructure, and molecular biology of cytoskeletal proteins are providing extremely detailed reconstructions of the pathogenesis of experimental models of neurological disorders. A major challenge lies in the extension of these approaches to clinical studies.
The inheritance of alzheimer's disease: A new interpretation
Authors: Fitch Naomi , Becker Rubin , Heller Anita
Published: January 2005

Ninety‐one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty‐nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one‐third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.
Quantitative relations between hypertonia and stretch reflex threshold in spastic hemiparesis
Authors: Powers R. K. , Marder‐Meyer J. , Rymer W. Z.
Published: January 2005

The relative contributions of variations in stretch reflex threshold and total joint stiffness to changes in stretch‐evoked torque were assessed in the spastic elbow muscles of 14 hemiparetic spastic subjects. For a given subject, variations in torque, measured after a constant angular deflection, were mediated largely by changes in stretch reflex threshold, rather than by changes in reflex stiffness. Between‐subject comparisons were sensitive to stiffness differences between limbs, but reflex thresholds were still broadly correlated with torque magnitude, suggesting that reductions in stretch reflex threshold are uniformly present in spastic muscles. These findings, coupled with the apparent similarity of reflex stiffness estimates in voluntarily activated spastic and normal muscles, suggest that the central disturbance in spasticity is a reduction in the threshold of the stretch reflex, without a significant enhancement of reflex gain.
Focal spike‐induced cerebral dysfunction is related to the after‐coming slow wave
Authors: Shewmon D. Alan , Erwin Roland J.
Published: January 2005

By means of a computerized system of spike detection, presentation of visual stimuli, and registration of reaction times (RTs), we have shown previously that focal posterior interictal spikes cause transiently prolonged RT and increased nonperception and misperception of stimuli, especially contralateral to the spike. We report here the temporal profile of this phenomenon, ascertained by systematically increasing a delay between spike and stimulus‐flash, until the latter was well beyond the limits of the entire spike‐wave complex. In each of two subjects, the spike effect began just before the spike and ended with the termination of the after‐coming slow wave. For stimuli with identical delays following spikes, RTs were significantly prolonged if the end of the slow wave overlapped the stimulus, and not otherwise. In one subject, who had an amplitude dissociation between spikes and after‐coming slow waves, the prolongation of RT was associated with the larger waves, regardless of spike amplitude. These findings suggest that the after‐coming slow wave (surround hyperpolarization) transiently disrupts aspects of cortical functioning, in addition to whatever effect the spike itself may have. Focal spike‐wave‐induced cortical dysfunction may be relevant to a variety of interictal cognitive disorders.
Monoclonal antibody analysis of mononuclear cells in myopathies. IV: Cell‐mediated cytotoxicity and muscle fiber necrosis
Authors: Arahata Kiichi , Engel Andrew G.
Published: January 2005

Cell‐mediated muscle fiber injury occurs in inclusion body myositis (IBM), polymyositis (PM), and even in Duchenne dystrophy (DD). Most of the autoaggressive cells are T cells and macrophages, but some are killer/natural killer (K/NK) cells. We here compare the frequencies per 1,000 muscle fibers of endomysial K/NK cells of varying cytotoxicity with those of T cells and macrophages in 8 cases each of IBM, PM, and DD. Two‐micrometer serial cryostat sections were analyzed. The Leu‐4 marker, present on all T cells and some K/NK cells, and the Leu‐7 and Leu‐11 markers, present on K/NK cells, were localized by paired immunofluorescence. Macrophages were demonstrated by the acid phosphatase reaction. In IBM, PM and DD, the respective average cell counts per 1,000 muscle fibers were: Leu‐4+7− cells (T cells not expressing a K/NK marker)—710, 530, and 59; Leu‐4+7+ cells (K/NK cells of low K/NK cytotoxicity)—294, 163, and 13; Leu‐4−7+ cells (K/NK cells of intermediate cytotoxicity)—32, 10, and 2; and macrophages—292, 251, and 38. Leu 11+ K/NK cells that have the highest killing activity were virtually absent in all cases. The data suggest a limited role for antigen and major histocompatibility complex unrestricted K/NK cells, as compared with antigen‐specific and major histocompatibility complex‐restricted T cells, in IBM and PM. Further, the findings cast doubt on the significance of either T cells or K/NK cells in mature muscle in DD. We also determined the frequencies of nonnecrotic muscle fibers invaded by mononuclear cells (i.e., fibers affected by cell‐mediated cytotoxicity) and of necrotic fibers, for these frequencies are indicators of two major mechanisms of muscle fiber injury in myopathies. Nonnecrotic invaded fibers were 5.5 times more frequent than necrotic fibers in IBM; the converse was true in DD; and the two mechanisms were equally frequent in PM.
Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigens
Authors: Schmidt M. L. , Gur R. E. , Gur R. C. , Trojanowski J. Q.
Published: January 2005

We examined the possibility that neurofibrillary tangles (NFTs) were heterogeneous in postmortem hippocampus from 22 patients with or without senile dementia of the Alzheimer type. Intraneuronal NFTs and extracellular, or “ghost”, NFTs were recognized in situ by only one or the other of two monoclonal antibodies. The first monoclonal antibody, RMO87, stained only intraneuronal NFTs and is specific for phosphate‐dependent epitopes in tau and the two high molecular weight neurofilament proteins. The second monoclonal antibody, 2.2B10, is specific for glial fibrillary acidic protein, and it stained only the RMO87‐negative extracellular NFTs. Treatment of sections with alkaline phosphatase or sodium dodecyl sulfate, and the isolation of NFTs from hippocampus, did not expose RMO87 binding sites in extracellular NFTs. These observations indicate that neurofilament‐like and tau‐like epitopes can be lost from NFTs in situ, and that at least two populations of morphologically and immunochemically distinct NFTs exist.
Two distinct deficits of visual tracking caused by unilateral lesions of cerebral cortex in humans
Authors: Thurston Stephen E. , Leigh R. John , Crawford Trevor , Thompson Alan , Kennard Christopher
Published: January 2005

We studied horizontal visual tracking in 20 patients with unilateral cerebral lesions and in 10 age‐matched control subjects. Five patients, all with posterior lesions, showed impaired smooth pursuit of predictable targets moving toward the side of the cerebral lesion. Using nonpredictable step‐ramp stimuli, we identified two distinct deficits of visual tracking. The first was a unidirectional deficit of smooth pursuit, for targets moving toward the side of the lesion, in response to stimuli presented into either visual hemifield. The second deficit, identified in a sixth patient who did not show pursuit asymmetry to predictable targets, was a bidirectional inability to estimate the speed of a moving target in the visual hemifield contralateral to the side of the lesion; this caused inaccurate saccades to moving (but not stationary) targets and impaired smooth pursuit initiation. These visual tracking deficits were independent of homonymous hemianopia or hemispatial neglect. These two tracking deficits are similar to those described in rhesus monkeys with lesions of the medial superior temporal and middle temporal visual areas.
Clinical and electrophysiological studies of human immunodeficiency virus—seropositive men without AIDS
Authors: Smith T. , Jakobsen J. , Gaub J. , Helweg‐Larsen S. , Trojaborg W.
Published: January 2005

Motor weakness and ataxia of lower limbs and abnormalities of somatosensory evoked potentials occur in many patients with the acquired immunodeficiency syndrome (AIDS). We studied 15 human immunodeficiency virus‐seropositive subjects without AIDS and found no clinical neurological abnormalities. The mean latency of the brainstem auditory evoked potential (peak V) was increased, suggesting a central defect. Despite normal peripheral nerve conduction along the tibial nerve, the mean latency of the spinal cord potential of the twelfth thoracic vertebra was increased compared with normal, possibly indicating an incipient conduction defect at or near the spinal root ganglion or lumbar spinal cord.
Stimulation of lipolytic enzymes in alzheimer's disease
Authors: Farooqui Akhlaq A. , Liss Leopold , Horrocks Lloyd A.
Published: January 2005

The activities of monoacylglycerol and diacylglycerol lipases were 6 to 8 times higher in plasma membrane and synaptosomal plasma membrane fractions of nucleus basalis from patients with Alzheimer's disease than in those membranes from normal human brains. Membranes from the hippocampus region of Alzheimer‐affected brains also showed consistently higher activities of monoacylglycerol and diacylglycerol lipases than those from control brains. These results indicate a stimulation of lipolytic enzymes in nucleus basalis and hippocampus regions in patients with Alzheimer's disease.
Motor conduction studies in guillain‐barré syndrome: Description and prognostic value
Authors: Cornblath David R. , Mellits E. David , Griffin John W. , McKhann Guy M. , Albers James W. , Miller Robert G. , Feasby Thomas E. , Quaskey Shirley A. ,   The Guillain‐Barré Syndrome Study Group
Published: January 2005

The North American study of plasmapheresis in Guillain‐Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 days of illness. For each parameter of motor conduction data, means were computed based on institutional normal data. Mean distal motor and F wave latencies commonly were abnormal in these early studies. In univariate analysis, mean compound muscle action potential (CMAP) amplitude from distal and proximal stimulation and mean motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction parameters, mean distal CMAP amplitude was the single best predictor of prognosis; other measures did not add to its predictive value. In further multivariate analysis of all factors relating to outcome, mean distal CMAP amplitude was determined to be the most powerful predictor of outcome, followed by plasmapheresis. These two factors were always statistically significant over and above all other variables. Our results indicate that prognostic information can be obtained from motor conduction studies even when performed early in the course of GBS; a mean distal CMAP amplitude of 0 to 20% of the lower limit of normal is associated with a markedly increased probability of a poor outcome. Nevertheless, even in patients with a low mean distal CMAP amplitude, the predicted outcome is improved with plasmapheresis therapy.
Clinical and neuropathological findings in systemic lupus erythematosus: The role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura
Authors: Devinsky Orrin , Petito Carol K. , Alonso Daniel R.
Published: January 2005

We reviewed the medical records and autopsy reports of 50 patients with systemic lupus erythematosus to determine the clinical and neuropathological features of this disease. Neuropsychiatric disturbances were found in the majority (74%) of the patients, occurring as psychiatric illness only (5 patients), neurological idsorders only (15 patients), and both together (17 patients). Central nervous system (CNS) lesions were present in half the patients; embolic brain infarcts (10 patients) and CNS infections (8 patients) were the most common. Cardiac sources of emboli were Libman‐Sacks endocarditis (5 patients), chronic valvulitis (2 patients), and left side of heart mural thrombus (2 patients). There was no evidence of active CNS vasculitis. Clinical features of thrombotic thrombocytopenic purpura (TTP) developed during the terminal illness in 14 patients, 7 of whom also had pathological evidence of TTP. Correlation between neuropsychiatric disorders and brain lesions could be made in approximately half the patients. This study indicates that cardiac emboli from Libman‐Sacks endocarditis and TTP are common pathogenetic factors of CNS disease in systemic lupus erythematosus, whereas CNS vasculitis is rare.
Prolonged deterioration of ischemic brain energy metabolism and acidosis associated with hyperglycemia: Human cerebral infarction studied by serial 31P NMR spectroscopy
Authors: Levine Steven R. , Welch K. M. A. , Helpern J. A. , Chopp Michael , Bruce Randal , Selwa James , Smith Michael B.
Published: January 2005

We report on a patient with a large ischemic hemispherical stroke studied serially by 31P nuclear magnetic resonance spectroscopy. Persistent hyperglycemia was associated with prolonged acidosis in ischemic brain and failure of high‐energy phosphate metabolism to recover. These in vivo human data support the concept that hyperglycemia adversely affects ischemic brain metabolism, pH, and clinical outcome.
Subcortical neglect: Neuropsychological, SPECT, and neuropathological correlations with anterior choroidal artery territory infarction
Authors: Bogousslavsky Julien , Miklossy Judit , Regli Franco , Deruaz Jean‐Pierre , Assal Gil , Delaloye Bernard
Published: January 2005

In 2 patients with infarction in the territory of the right anterior choroidal artery, hemiparesis, hemihypesthesia (in 1), and hemianopia or superior quadrantanopia were associated with severe multimodal hemineglect, without anosognosia, disorientation, or asomatognosia. Single‐photon emission tomography showed that marked hypoperfusion was not limited to the right posterior capsular region, but also involved the overlying parietal cortex, and to a lesser extent the frontal cortex. At autopsy in 1 patient, the infarct was nearly limited to the deep white matter of the temporal isthmus and the retrolenticular part of the internal capsule; only minute lesions were present in the globus pallidus, body of caudate, and amygdala. These findings are consistent with a disconnection phenomenon as the basis for subcortical neglect with ipsilateral deactivation of the parietofrontal cortex.
Peripheral neuropathy in myotonic dystrophy: A nerve biopsy study
Authors: Cros Didier , Harnden Patricia , Pouget Jean , Pellissier Jean Françlois , Gastaut Jean Louis , Serratrice Georges
Published: January 2005

Sural nerve biopsies from 13 unselected myotonic dystrophy patients and 6 normal controls were studied morphometrically. The myelinated fiber density was reduced in 11 of the 13 myotonic dystrophy patients, with preferential loss of large myelinated fibers. Unmyelinated fiber densities and diameters were normal. Teased fiber studies commonly revealed focal areas of remyelination and abnormal wrinkling of the myelin sheath. Measurement of internodal length disclosed features of both axonal regeneration and focal demyelination‐remyelination. These findings are consistent with a chronic axonopathy of moderate severity, possibly due to axonal atrophy.
Mild senile dementia of the alzheimer type: 2. Longitudinal assessment
Authors: Berg Leonard , Miller J. Philip , Storandt Martha , Duchek Janet , Morris John C. , Rubin Eugene H. , Burke William J. , Coben Lawrence A.
Published: January 2005

Forty‐three subjects with mild senile dementia of the Alzheimer type (SDAT, so‐called probable Alzheimer's disease) were studied longitudinally by serial administration of several tests to rate dementia. Comparison was made with 58 healthy elderly controls. The clinical diagnosis was confirmed in all 16 autopsies. At 5 years after entry into the study, the cumulative rate of nursing home placement was 73%, and of death, 30%, rising at 7 years to 84% and 44%, respectively. Four of six clinical measures of dementia were found to correlate with the natural history of SDAT. Several measures are better than a single one in carrying out longitudinal studies of the disorder.
Antimigraine drug interactions with serotonin receptor subtypes in human brain
Authors: Peroutka Stephen J.
Published: January 2005

The interactions of antimigraine agents with serotonin (5‐hydroxytryptamine, 5‐HT) receptor subtypes were analyzed in human frontal cortex membranes. The drugs studied included 5‐HT antagonists, beta‐adrenergic antagonists, and calcium channel blockers. At 5‐HT1A sites labeled by 3H‐8‐hydroxy‐2‐(N, N‐dipropylamino)‐tetralin, (–)pindolol, alprenolol, (–)propranolol, methysergide, cyproheptadine, and pizotifen are similar in that they display affinities of approximately 100 nM for this receptor. By contrast, only methysergide displays relatively high affinity (120 ± 60 nM), whereas all other drugs have affinities greater than 1,000 nM for non‐5‐HT1A sites labeled by 3H‐5‐HT in human cortex. Finally, at 5‐HT2 receptors labeled by 3H‐spiperone, cyproheptadine, methysergide, and pizotifen are extremely potent agents (affinity constants of 1 to 10 nM), whereas amitriptyline (23 ± 4 nM), verapamil (140 ± 50 nM), and nifedipine (320 ± 80 nM) are moderately potent. All other drugs are inactive at concentrations below 1,000 nM. These data demonstrate that most antimigraine drugs display high affinity for the 5‐HT1A and/or 5‐HT2 receptor subtypes in human brain. However, antimigraine efficacy cannot be explained by drug interactions with a single 5‐HT receptor subtype.
Motor neuron syndrome and monoclonal IgM with antibody activity against gangliosides GM1 and GD1b
Authors: Nardelli Ettore , Steck Andreas J. , Barkas Thomas , Schluep Myriam , Jerusalem Felix
Published: January 2005

We demonstrated that an IgM M‐protein from a patient with motor neuron syndrome had antibody activity against gangliosides GM1, GD1b, and asialo GM1. Studies with a sugar‐binding lectin suggested that the epitope in the patient's M‐IgM involved the Gal(β1‐3) GalNAc moiety. Immunohistological techniques demonstrated staining of axons in the lumbar roots, granular cells, and white matter in the cerebellum by the patient's M‐IgM. We propose that, in this case, an autoimmune mechanism of motor neuron syndrome associated with a monoclonal protein is most likely.
Positron emission tomographic scan investigations of Huntington's disease: Cerebral metabolic correlates of cognitive function
Authors: Berent Stanley , Giordani Bruno , Lehtinen Shirley , Markel Dorene , Penney John B. , Buchtel H. A. , Starosta‐Rubinstein Simon , Hichwa Richard , Young Anne B.
Published: January 2005

Fifteen drug‐free patients with early to mid‐stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18F‐2‐fluro‐2‐deoxy‐D‐glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p < 0.001) and putamen (p < 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual‐spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain‐behaviour relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.
Thalamic astasia: Inability to stand after unilateral thalamic lesions
Authors: Masdeu Joseph C. , Gorelick Philip B.
Published: January 2005

Inability to stand in the absence of motor weakness or marked sensory loss is usually considered to reflect midline cerebellar disease. However, the 15 patients reported here had astasia related to unilateral thalamic lesions, documented by autopsy and computed tomography in 2 patients and by computed tomography in 13. The lesions, including infarction (6), hemorrhage (7), and tumor (2), involved primarily the superoposterolateral portion of the thalamus, but spread the rubral region. Alert, with normal or near‐normal strength on isometric muscle testing and a variable degree of sensory loss, the patients could not stand and 7 of them could not sit up unassisted. They fell backwards or toward the side contralateral to the lesion. They appeared to have a deficit of overlearned motor activity of an axial and postural nature. In the vascular cases, the deficit improved in a few days or weeks. However, these patients had a tendency to sustain falls during the rehabilitation period.
Possible neurotransmitter basis of behavioral changes in alzheimer's disease
Authors: Palmer Alan M. , Stratmann Gary C. , Procter Andrew W. , Bowen David M.
Published: January 2005

Serotonin, 5‐hydroxyindoleacetic acid, and homovanillic acid concentrations have been determined in 10 areas of the cerebral cortex from 17 subjects with Alzheimer's disease and 18 control subjects. The dopamine metabolite was not reduced in any area, whereas both indoleamines were reduced in the superior frontal, inferior temporal, and fusiform gyri, and the temporal pole. These areas and areas of the parietal cortex, where there were no changes in concentration, have not previously been reported on. We argue that the large loss of indoleamines from the frontal lobe (to 50–63% of control values) is rather unexpected based on other biochemical measurements and may relate to behavioral changes.
A potential role for excitotoxins in the pathophysiology of spinal cord injury
Authors: Faden Alan I. , Simon Roger P.
Published: January 2005

It has been proposed that endogenously released excitatory amino acids may contribute to injury of the central nervous system in a variety of disorders including certain neurodegenerative diseases, epilepsy, and cerebral ischemia. In the present studies we evaluated the hypothesis that excitatory amino acids, acting at the N‐methyl‐D‐aspartate (NMDA) receptor, contribute to secondary tissue damage following traumatic spinal cord injury. Administration of NMDA, adjacent to the trauma site, significantly worsened the outcome after thoracic cord injury in rats, whereas its stereoisomer, N‐methyl‐L‐aspartate (NMLA), was without effect. Systemic treatment with MK‐801—a selective, centrally active, NMDA antagonist—significantly improved neurological outcome after trauma. These findings extend the excitotoxin concept to central nervous system trauma and indicate that NMDA antagonists may be beneficial in the treatment of traumatic spinal cord injury.
Reduction of monocyte 5′nucleotidase activity by γ‐interferon in multiple sclerosis and autoimmune diseases
Authors: Armstrong Marilyn A. , Shah Soraya , Hawkins Stanley A. , Bell Aubrey L. , Roberts Stanley D.
Published: January 2005

Ecto‐5′nucleotidase (5′NT) activity in the plasma membrane of peripheral blood monocytes from patients with multiple sclerosis (MS), rheumatoid arthritis (RA), myasthenia gravis (MG), motor neuron disease (MND), and from normal control subjects of similar age was determined by radioisotopic assay. The activity in unstimulated monocytes cultured for 24 and 48 hours was found to be higher than normal in 56% of patients with active relapsing MS, 29% of patients with RA, and 7% of patients in the MG/MND group. While the enzyme activity was reduced after cultivation of the cells with recombinant interferonrγ(γ‐IFN) in all of the groups studied, the percentage reduction was significantly greater in monocytes from patients with active relapsing MS who were in relapse at the time of sampling (p= 0.03). HLA‐DR expression was monitored using immunofluorescence staining with monoclonal antibody and showed that similar numbers of monocytes in all patient and control groups expressed this antigen. Thus, while high monocyte 5′NT activity was found principally in patients with active relapsing MS and in some patients with RA, the monocytes from patients with MS were, in addition, exquisitely sensitive to stimulation withγ‐IFN.
Functional hemispherectomy for treatment of epilepsy associated with hemiplegia: Rationale, indications, results, and comparison with callosotomy
Authors: Tinuper Paolo , Andermann Frederick , Villemure Jean‐Guy , Rasmussen Theodore B. , Quesney Luis Felipe
Published: January 2005

Hemispherectomy is effective in arresting seizures associated with maximal or near maximal hemiparesis. This procedure, however, carries an unacceptable 33% risk of late complications due to cerebral hemosiderosis. Anatomically partial but functionally complete hemispherectomy was devised to avoid these complications. The frontal or occipital lobes, or both, were left in place with the blood supply intact but with connections to commissures and brainstem divided. The central strip and parietal and temporal lobes were removed. Twenty patients were so treated with a follow‐up of 4 to 13 years (average, 7.3 years) in 14. Ten of these are seizure free, 1 had a single nOctoberurnal seizure, 1 had occasional focal twitching, and 2 had a worthwhile but lesser reduction in the seizure tendency. None has developed cerebral hemosiderosis, to date. In appropriately selected patients, functional hemispherectomy is an effective procedure preferable to callosotomy or to partial hemispherectomy. When there is no independent ictal discharge from the opposite hemisphere, arrest of seizures may be expected, leading to improvement in cognitive functioning (mean increase, 10 IQ points), social behavior, and a reduction in or discontinuation of anticonvulsant medication. In these patients, gait and hand use remain unchanged.
Asymbolia for pain: A sensory‐limbic disconnection syndrome
Authors: Berthier Marchcelo , Starkstein Sergio , Leiguarda Ramon
Published: January 2005

We describe the behavioral and neuroanatomical features of asymbolia for pain occurring in 6 patients following unilateral hemispheric damage secondary to ischemic lesions in 5 and traumatic hematoma in 1. In the absence of priMarchy sensory deficits, these 6 patients showed a lack of withdrawal and absent or inadequate emotional responses to painful stimuli applied over the entire body, as well as to threatening gestures. Five patients also failed to react to verbal menaces. Patients appeared unconcerned about the defect and seemed unable to learn appropriate escape or protective responses. Common associated abnormalities were rapidly resolving hemiparesis, cortical‐type sensory loss, unilateral neglect, and body‐schema disorders. Neuroradiological examination disclosed left hemispheric lesions in 4 patients and right hemispheric involvement in 2. Although lesion extension differed, the insular cortex was invariably damaged in all 6 patients. These findings suggest that insular damage may play a critical role in the development of the syndrome by interrupting connections between sensory cortices and the limbic system.
Clinically diagnosed Alzheimer's disease: Autopsy results in 150 cases
Authors: Joachim C. L. , Morris J. H. , Selkoe D. J.
Published: January 2005

One hundred fifty autopsy brains from patients with clinically diagnosed Alzheimer's disease (AD) were examined pathologically. The brains were received consecutively over a 3‐year period from numerous sources as part of research program in which one brain half was frozen for biochemical studies and the other half was fixed in formalin One hundred thirty‐one (87%) of the 150 cases fulfilled histological criteria for AD, with or without additional findings, such as Parkinson's disease or stroke. At least a minimal degree of amyloid angiopathy was found in every brain showing histopathological abnormalities of AD. Twenty‐three (18%) of the 131 AD brains had Lewy bodies in neurons of the substantia nigra. Thirteen of the 19 non‐AD cases were diagnosed as other neurodegenerative disorders. In only 2 cases was no histological correlate for the patient's dementia found. We conclude that (1) the many physicians who diagnosed these cases did so highly accurately; (2) degenerative changes in the substantia nigra were more common in patients with AD than has been reported for the general aged population; (3) amyloid angiopathy was a constant accompaniment of AD, although its severity varied widely; (4) vascular dementia was rarely clinically misdiagnosed as AD; (5) neuropathological findings were insufficient to account for the clinical syndrome of dementia in less than 2% of cases; (6) the histological criteria established by the National Institutes of Health/American Association of Retired Persons Research Workshop on the Diagnosis of Alzheimer's Disease worked well in assessing this large series.
A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside
Authors: Pestronk A. , Cornblath D. R. , Ilyas A. A. , Baba H. , Quarles R. H. , Griffin J. W. , Alderson K. , Adams R. N.
Published: January 2005

We report 2 patients with a treatable, immune‐mediated motor polyneuropathy associated with antibodies to defined neural antigens. In these patients asymmetrical weakness developed in one arm and progressed over 2 to 3 years to involve the other arm, legs, and trunk. Both patients were initially diagnosed as having lower motor neuron forms of amyotrophic lateral sclerosis. However, repeated electrophysiological testing eventually showed multifocal conduction blocks in motor but not sensory fibers compatible with patchy selective demyelination. Serum testing by thin‐layer chromatography and enzyme‐linked immunosorbent assay revealed that both patients had high titers of antibody directed against GM1 and other gangliosides. Initial therapeutic trials of prednisone (100 mg daily for 4 to 6 months) and plasmapheresis were unsuccessful. Treatment with cyclophosphamide, however, was followed by Marchked improvement in strength in both patients.
Multiple sclerosis: Involvement of interferons in lesion pathogenesis
Authors: Traugott Ute , Lebon Pierre
Published: January 2005

To investigate a possible role of interferons (IFNs) in lesion pathogenesis, central nervous system tissue from multiple sclerosis patients and control subjects was stained by immunocytochemical techniques in combination with monoclonal antibodies or polyclonal antisera for the demonstration of IFN‐α, IFN‐β, and IFN‐γ. The results were correlated to lesion activity, to the presence of class I and class II major histocompatibility antigen‐positive astrocytes, and to the composition of cellular infiltrates. IFNs were detectable in active but not in inactive chronic multiple sclerosis lesions. In acute multiple sclerosis plaques, all three types of IFN were widely distributed on glial elements and infiltrating cells. In active chronic multiple sclerosis, labeling of cells for IFN‐α, IFN‐β, and IFN‐γ was most pronounced at the lesion edge and displayed distinct distribution patterns. Overall, IFN‐γ was more common than IFN‐α, IFN‐β, and was predominantly found on astrocytes. IFN‐α, was detectable mainly on macrophages. Distribution of IFN‐β, partially overlapped with that of IFN‐γ and IFN‐β, in that it was present on some astrocytes and on some macrophages. IFNs were rare in normal white matter remote from lesions and in the gliotic lesion center. La antigen and human leukocyte antigen ABC on astrocytes were distributed similarly to IFN‐γ and IFN‐β, respectively. These findings indicate that IFN‐γ may play a role in active lesion growth in multiple sclerosis, whereas IFN‐α and IFN‐β may exert some local immunosuppressive effect. IFNs were also detectable in central nervous system tissue from patients with some other neurological diseases but were virtually absent from tissue from normal control subjects.
Inflammatory lesions of peripheral nerve in a patient with human T‐lymphotropic virus type I‐associated myelopathy
Authors: Said Gérard , Goulon‐Goeau Catherine , Lacroix Catherine , Fève Anaic , Descamps Hélène , Fouchard Marchie
Published: January 2005

In a patient with tropical spastic paraparesis associated with a positive titer for human T‐lymphotropic virus type I, electrophysiological study detected a mixed, axonal and demyelinating, multifocal neuropathy. Perineural and perivascular infiltrates, moderate axon loss, wallerian degeneration, and demyelinating lesions of isolated fibers were present in the nerve biopsy specimen. These inflammatory lesions resembled those found in the central nervous system of patients with tropical spastic paraparesis.
Oligoclonai IgG bands in cerebrospinal fluid and serum during asymptomatic human immunodeficiency virus infection
Authors: Grimaldi L. M. E. , Castagna A. , Lazzarin A. , Pristerá R. , Bianchi G. , Moroni M. , Roos R. P.
Published: January 2005

Serum and cerebrospinal fluid (CSF) samples from asymptomatic patients seropositive for human immunodeficiency virus (HIV) showed frequent evidence of intrathecal IgG synthesis and oligoclonai IgG bands, with different isoelectric focusing patterns in serum and CSF; 2 of 7 had a CSF pleocytosis. The results suggest frequent, early, chronic central nervous system infection following HIV infection.
Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, Part I
Authors: Fabbnni G. , Mouradian M. M. , Junecos J. L. , Schlegel J. , Mohr E. , Chase T. N.
Published: January 2005

The duration of the antiparkinsonian action of levodopa was studied in 48 patients with various response patterns to the oral administration of the dopamine precursor. Deterioration in motor scores after abrupt cessation of a steady‐state intravenous levodopa infusion occurred at two successive rates: an initial rapid phase followed by a terminal slower phase. Efficacy half‐time Decemberreased and initial efficacy Decemberay slope increased with progression of levodopa response groups from never treated to stable responders, and then to fluctuating responders of the wearing‐off type and finally of the on‐off type. Efficacy half‐time exceeded plasma levodopa half‐life in the 2 nonfluctuating groups, approximated it in those patients with wearing‐off responses, and was significantly shorter in patients with fluctuations of the on‐off type. The half‐times for the Decemberline in antiparkinsonian efficacy and dyskinesia severity differed significantly, suggesting different pharmacological mechanisms. Motor fluctuation severity correlated best with initial efficacy Decemberay slope, and both were best predicted by parkinsonian symptom severity. The dyskinesia Decemberay rate correlated most closely with levodopa dose. These results support the view that progressive dopamine neuron degeneration reduces the brain's ability to buffer shifts in levodopa availability attending its periodic oral administration; the clinical result is wearing‐off phenomenon. The on‐off phenomenon as well as dyskinesia apparently reflects additional secondary changes related to levodopa therapy and occurring postsynaptically.
Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II
Authors: Mouradian M. M. , Junecos J. L. , Fabbrini G. , Schlegel J. , Bartko J. J. , Chase T. N.
Published: January 2005

The contribution of central pharmacodynamic mechanisms to the pathogenesis of motor fluctuations in advanced Parkinson's disease was studied in 29 patients by evaluating their acute response to intravenously injected. levodopa. While the threshold dose for an antiparkinsonian effect did not change, that for induction of dyskinesia showed a progressive reduction in 4 groups: (1) levodopa‐naive patients, (2) those with a stable response to oral administration, and (3) those with wearing‐off or (4) on‐off fluctuations. Concomitantly, the therapeutic window for levodopa narrowed and the levodopa dose—antiparkinsonian response slope increased. The antiparkinsonian threshold dose correlated best with duration of symptoms; the dyskinesia threshold dose, therapeutic window, and dose‐response slope related most closely with the duration of levodopa treatment. The differing dose‐response profiles for the antiparkinosonian and dyskinetic effects suggest involvement of Septemberarate pharmacological mechanisms. The present results, taken together with previous observations that the wearing‐off phenomenon responds promptly to plasma levodopa stabilization while on‐off fluctuations tend to diminish over several days, suggest that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and motor fluctuations, especially of the on‐off type, which complicate levodopa therapy of patients with advance Parkinson's disease.
In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion
Authors: Uematsu Daisuke , Greenberg Joel H. , Reivich Marchtin , Karp Andrea
Published: January 2005

An increase in cytosolic free calcium concentration ([Ca2 +]i) may trigger irreversible cell injury following cerebral ischemia. We have measured changes in [Ca2 +]i in cat cortex in vivo during ischemia produced by 1 hour of middle cerebral artery occlusion and during 30 minutes of reperfusion. Indo‐1, a fluorescent Ca2+ indicator, was loaded into the exposed cortex by superfusion, and changes in the [Ca2+]i signal (400/506 nm ratio)were measured microfluorometrically during ultraviolet excitation (340 nm). The nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) redox state and hemodynamic changes were measured simultaneously. The animals showing severe deterioration in their electroencephalograms (EEG) showed a progressive increase in the [Ca2+]i signal during ischemia (baseline: 1.46 0.05; 60 minutes after occlusion: 2.99 0.37; n = 7). At 30 minutes following reperfusion, the animals showing little recovery in their EEG exhibited a further increase in [Ca2+}i (4.71 0.87,n = 3), whereas animals showing significant recovery in their EEG also showed recovery of {Ca2+]i(1.55 0.09, n = 4). By contrast, the moderate or mild stroke animals with less deterioration in their EEGs showed no increase in [Ca2+]i during either ischemia or reperfusion. These data suggest that the increase in [Ca2+]i might be closely related not only to deterioration of brain function during ischemia but also to poor recovery during the reperfusion period.
Recording of movement‐related potentials from the human cortex
Authors: Neshige Ryuji , Lüders Hans , Friedman Lee , Shibasaki Hiroshi
Published: January 2005

A patient with intractable epilepsy secondary to a brain tumor was evaluated with a chronically implanted array of 64 stainless‐steel subdural electrodes covering the perirolandic area. Cortical potentials associated with voluntary, selfpaced middle‐finger extension were recorded simultaneously from subdural and scalp electrodes using a computerassisted method for averaging movement‐related potential (MRP) in relation to electromyographic (EMG) onset. A high‐amplitude negative potential, Bereitschaftspotential/negative slope (BP/NS′), preceding the onset of the EMG activity by more than 1 sec was recorded in an extremely localized fashion exclusively from electrodes placed in the precentral hand motor area as well as in the more medial part of the somatosensory hand area. These results suggest that the hand motor and sensory areas have an essential participation in the generation of MRPs and, therefore, also in the preparation of voluntary finger movements.
A double‐blind randomized crossover trial of bromocriptine and placebo in restless legs syndrome
Authors: Walters Arthur S. , Hening Wayne A. , Kavey Neil , Chokroverty Sudhansu , Gidro‐Frank Steve
Published: January 2005

A double‐blind randomized crossover study of 7.5 mg bromocriptine at bedtime versus placebo was conducted in 30‐day phases (with a 2‐week washout period between phases) in 6 patients with idiopathic restless legs syndrome. Five patients experienced partial subjective improvement in restlessness and paresthesias on bromocriptine as opposed to placebo and expressed a desire to continue on the medication. On bromocriptine, the patients showed polysomnographically a mean Decemberrease of 43% from control and a mean Decemberrease of 57% from placebo in the number of periodic movements of sleep per hour of sleep (p < 0.025). Two of 3 patients with abnormally Decemberreased total sleep time and sleep efficiency showed an improvement in these measures on therapy. The dopamine agonist bromocriptine may be a useful therapy in some patients with restless legs syndrome.
Leukoencephalopathy among native indian infants in northern Quebec and Manitoba
Authors: Black Deborah N. , Booth Fran , Watters Gordon V. , Andermann Eva , Dumont Charles , Halliday William C. , Hoogstraten J. , Kabay Michel E. , Kaplan Paige , Meagher‐Villemure Kathleen , Michaud Jean , O'gorman Gus
Published: January 2005

We report 14 cases of a severe familial leukoencephalopathy among native North American Indian infants in northern Quebec and Manitoba. Affected infants have hypotonia and mild motor delay, followed by seizures, hypotonia or spasticity, eye deviation, and abnormal posture during a Februaryrile illness around 6 months of age. Death follows a rigid, vegetative state that manifests days to months after disease onset and is Marchked in some cases by prominent autonomic disturbances, blindness, and cessation of head growth. Symmetrical hemispheric white matter lucencies and diffuse hypomyelination of the cerebral hemispheres and brainstem are the radiological and pathological hallMarchks. This disease differs from the known diseases of cerebral myelin. An autosomal recessive pattern of inheritance awaits statistical confirmation. The proposed cause is a delay in development or abnormal turNovemberer of central nervous system myelin.