bluuebunny/crossref_metadata_2025 huggingface dataset:
Disturbance of smooth pursuit caused by infarction of occipitoparietal cortex
Authors: Leigh R. John , Tusa Ronald J.
Published: January 2005

Two distinct deficits of ocular smooth pursuit could be demonstrated using two types of visual stimulus motion in a patient who had suffered bilateral occipitoparietal lobe infarction. First, in response to constant‐velocity (zero accleration) target motion, smooth pursuit gain (eye velocity/target velocity) was mildly impaired for tracking to the right but near normal for tracking to the left. For example, for a target moving at 28.5 degrees/sec, gain was 0.65 to the right but 0.85 to the left. Second, in response to high‐acceleration sinusoidal target motion, there was a deficit in maximum eye acceleration for targets moving right and left. The patient was unable to accelerate his eyes faster than 48 degrees/sec2 to the right and 95 degrees/sec2 to the left (normal is more than 300 degrees/sec2). It is suggested that smooth pursuit should be routinely tested using stimuli with a wide range of accelerations.
Regional perfusion in normal and ischemic rat sciatic nerves
Authors: Sladky John T. , Greenberg Joel H. , Brown Mark J.
Published: January 2005

We measured regional blood flow in rat sciatic‐posterior tibial nerve using an iodo‐[14C] antipyrine autoradiographic unique. Average flow was 12.1 ± 3.3 ml/100 gm/min, considerably less than that of both gray and white matter structures in the cerebral hemispheres. Perfusion was homogenous along the proximal‐distal extent of this nerve and along its radial axis. Acute occlusion of the femoral artery reduced regional sciatic blood flow. Flow was especially depressed within the endoneurial core of the proximal posterior tibial branch, which lies in a watershed zone between adjacent segmental arterial fields. The topography of the arterial supply to nerves and their abundant collateral circulation may explain the centrifascicular distribution of nerve infarcts, and in part can account for the apparent resistance of peripheral nerves to ischemia.
Herpes simplex virus type 2 encephalitis in two homosexual men with persistent lymphadenopathy
Authors: Dix Richard D. , Waitzman David M. , Follansbee Stephen , Pearson Brion S. , Mendelson Terri , Smith Peggy , Davis Richard L. , Mills John
Published: January 2005

Within a 5‐month period, 2 homosexual men with persistent lymphadenopathy developed clinical findings consistent with herpes simplex virus (HSV) encephalitis. These signs included abrupt change in mental status, seizures, cerebrospinal fluid pleocytosis, and localized electroencephalographic abnormalities showing temporal lobe involvement. Intial computed tomographic scans were unremarkable. Treatment with adenine arabinoside was instituted and temporal lobe biopsies were performed. Although virus‐specific antigens were detectable in only 1 patient, cultures of biopsy tissue from both patients yielded HSV type 2 organisms. Spiking fevers persisted and the patients failed to improve, prompting administration of acyclovir. Both patients recovered gradually after their second course of antiviral therapy and survived with severe neurological deficits. These patients should raise concerns about an increased incidence of type 2 encephalitic illness among homosexual men with persistent lymphadenopathy or acquired immune deficiency syndrome. In addition, the importance of using HSV type 2 antibody in the immunofluorescence test of brain biopsy tissue for rapid diagnosis of the disease is emphasized.
Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury
Authors: Faden Alan I. , Molioneaux Christopher J. , Rosenberger John G. , Jacobs Thomas P. , Cox Brain M.
Published: January 2005

It has been postulated that endogenous opioids play a pathophusiological role in spinal cord injury, based on the therapeutic effects of the opiate receptor antagonist naloxone in certain experimental models. The high doses of naloxone required to exert a therapeutic action suggest that naloxone's effects may be mediated by non‐μ opiate receptors, such as the κ receptor. This notion is supported by recent than naloxone in improving outcome after spinal cord injury. Moreover, dynorphin‐postulated to be the endogenous ligand for the κ receptor–is unique among opioids in producing hindlimn paralysis following intrathecal administration in the rat. In the present studies we have examined changes in endogenous opioid immunoreactivity following traumatic spinal cord injury in the rat. Dynorphin A was found to increase progressively with graded injury; changes were restricted to the injury segment and adjacent areas and were time dependent. Dynorphin A‐(1–8) showed no marked changes. Mehtionine and leucine enkephalin were either unaltered or reduced at the injury site; changes were not well localized and were not clearly related to the injury variables. These findings provide further support for a potential pathophysiological role of prodynorphin‐derived peptides in spinal cord injury.
An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain
Authors: Rex Sheu Kwan‐Fu , Kim Young‐Tai , Blass John P. , Weksler Marc E
Published: January 2005

The activity of the pyruvate dehydrogenase complex (PDHC; EC 1.2.4.1, EC 2.3.12, and EC 1.6.4.3) was reduced to about 30% of control values in histologically unaffected occipital cortex of the brains of patients with Alzheimer's disease, as well as in histologically affected frontal cortex. In contrast, activity of another mitochondrial enzyme, glutamate dehydrogenase, was normal. Neither age nor time untill postmortem study correlated significanctly with PDHC activity in either Alzheimer or control samples, and PDHC was not inactivated significantly on incubation with homogenates of either Alzheimer or control brain. Antibodies against the highly purified bovine PDHC inhibited Alzheimer and control PDHC equally per unit of enzyme activity. Immunoblots also indecated that the PDHC antigens were not different in normal and Alzheimer brain. This antibody, however, inhabited Alzheimer PDHC more effectively than it did control PDHC, based on milligrams of protien, suggesting a reduced amount of normal PDHC protien. Other data suggest that the PDHC deficiency is related to mitochondrial damege and to impaired calcium homeoestasis in Alzheimer nerve cells, which may then mediate a variety of other cellular impairments.
Hereditary motor sensory neuropathy type II with neurofilament accumulaion: New finding or new disorder?
Authors: Vogel P. , Gabriel M. , Goebel H. H. , Dyck P. J.
Published: January 2005

Peroneal muscular atrophy is now known to be heterogeneous and to be due to various underlying genetic mechanisms. Exploring this heterogeneity further, we report on a German kinship with the clinical, genetic, and nerve conduction features of hereditary motor and sensory neuropathy type II (HMSN type II) but whose sural nerves on biopsy were found to show infrequent axonal swellings with neurofilament accumulations not previously described. The dominant inheritance and absence of kinky hair set this disorder apart from giant axonal neuropathy. There was no history of toxic exposure to industrial chemicals. We conclude that the disorder either is a new type of HMSN or is HMSN type II with previously unencountered neurofilament accumulations. Neurofilament accumulation indicates that the axon could be a site for primary derangement and may implicate an abnormality of slow axonal flow. In addition, some of the patients exhibited features suggestive of a cardiomyopathy.
Experimental lead neuropathy: Inorganic lead inhibits proliferation but not diffrentiation of Schwann cells
Authors: Sobue Gen , Pleasure David
Published: January 2005

Schwann cells were prepared from the sciatic nerves of newborn rats and cultured in a monolayer. Addition of lead acetate at concentrations between 0.4 and 10.0 μmUg/ml, levels comparable to those occurring in neural tissues and physiological fluids of lead‐intoxicated rats, diminished both the baseline rate of proliferation of the Schwann cells and their response to the mitogens, axolemmal fragment, glial growth factor, and the adenosine 3′:5′‐cyclic monophosphate (cAMP) analogues 8‐bromo‐cAMP and dibutyryl‐cAMP. This demonstrates a direct toxic effect of inorganic lead on Schwann cell. Lead acetate in this concentration range did not, however, inhibit the cAMP analogue‐induced appearance of the “myelin marker” lipid galactocerebroside on the surfaces of the cultured Schwann cells.
Low cancer rates among patients with Parkinson's disease
Authors: Jansson Birger , Jankovic Joseph
Published: January 2005

Among 406 Patients with Parkinson's disease, the cancer rate (all sites combined) was about one‐third that for the general population. The risk of cancer increased during the treatment period but remained significantly low. Malignant and benign thyroid neoplasms were significantly more frequent than expected among patients with Parkinson's disease. We suggest that high level of total body potassium in patients with Parkinson's disease is the projective factor against cancer.
Mitochondrial myopathies
Authors: DiMauro Salvatore , Bonilla Eduardo , Zeviani Massimo , Nakagawa Masanori , DeVivo Darryl C.
Published: January 2005

Mitochondrial myopathies are clinically heterogeneous disorders that can affect multiple systems besides skeletal muscle (mitochondrial encephalomyopathies or cytopathies) and are usually defined by morphological abnormalities of muscle mitochondria. There are a few distinctive syndromes, such as the Kearns‐Sayre syndrome; myoclonus epilepsy with ragged‐red fibers; and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Biochemically, mitochondrial myopathies can be divided into defects of substrate utilization, oxidation‐phosphorylation coupling, and the respiratory chain. Because mitochondria have their own DNA and their own translation and transcription apparatuses, mitochondrial myopathies can be due to defects of either a nuclear or mitochondrial genome and can be transmitted by mendelian or maternal inheritance.
Human telencephalic angiogenis
Authors: Kuban Karl C. , Gilles Floyd H.
Published: January 2005

We provide new observations regardingthe histogenesis and regional development of the human telencephalic microvasculature during the last half of gestation. Endothelium‐lined trunks extending from pia to the subventricular plexus, evident early in gestation, persisit during the last half of gestation. The courses of these trunks are modified and become complex as the bulk of the telencephalon, straitum, and thalamus increases and as guri grow. New cerebral tissue is supplied by increasing numbers of shorter penetrating vessels. All extrastriatal vessels have many lateral right‐and acute‐angle branches that join nearby trunks and shorter vessels. Striatal vessel branches predominanatly have acute angles. Most extratriatal channels remain devoid of apparent muscular is until the final weeks of gestation. In gestation. In contrast, striatal arteries begin to muscularize at about 24 weeks of gestation. Muscularization appears to occur in a centripetal direction and is apparent in the caudate at approximately 30 weeks' gestation. We did not identify transventricular, paraventricular, or recurrent arteries ending in deep white matter.
Nucleus raphe dorsalis in Alzheimer's disease: Neurofibrillary tangles and loss of large neurons
Authors: Yamamoto Toru , Hirano Asao
Published: January 2005

Diffuse serotonergic fibers are presumed to project to the talencephalon from the nucleus raphe dorsalis (NRD) of the mid brain, in a manner similiar to the cholinergic projections from the nucleus basalis of Meynert (nbM) to the cerebral cortex. Neuropathological changes in both of these nuclei have been reported in Alzheimer's disease (AD). Although many morphometric studies of the nbM in AD have been documented, only one such study of the NRD has been documented, only one such study of the NRD has been conducted so far; it demonstrated a six fold increase in neurofibrillary tangles in AD but no statistically significant difference in the number of neurons in patients with AD and age‐matched controls. A study of the NRD utilizing different stains and wider anatomical boundaries is detailed in this report of 5 patients with AD and 7 age‐matched controls. In AD the NRD showed 39 times more neurofibrillary tangles and the number and cell density of large neurons were reduced to 23% and 28%, respectively, of those in the controls. A small number of senile plaques were found in the NRD in all patients with AD but none were found in the controls.
The clinical value of free phenytoin levels
Authors: Theodore William H. , Yu L. , Price Beth , Yonekawa Wayne , Porter R. J. , Kapetanovic I. , Moore Henry , Kupferberg Harvey
Published: January 2005

The relationship between total and free phenytoin levels and drug toxicity was studied in 80 patients. Twenty‐four were taking phenytoin alone. Drug toxicity was assessed by a “blind” rater using an eight‐point standardized scoring system. The mean free phenytoin fraction was 0.076 in patients taking phenytoin alone or phenytoin and carbamazepine and 0.11 in patients taking valproic acid (p < 0.001). The free fraction did not change with the total level over the range tested (6.7 to 39.9 μg/ml total phenytoin). There was a strong correlation between free and total levels (r = 0.84). Both free (r = 0.59) and total (r = 0.49) phenytoin levels were positively correlated with the toxicity score. Only total phenytoin levels showed a weak positive correlation with decreasing seizure frequency. Our results suggest that routine free phenytoin level monitoring is not necessary in most clinical situations.
Neuropathy and anti‐myelin‐associated glycoprotein IgM M proteins: T cell regulation of M protein secretion in vitro
Authors: Latov Norman , Godfrey Maurice , Thomas Yoland , Nobile‐Orazio Eduardo , Spatz Linda , Abraham Judith , Perman Gayle , Freddo Lorenza , Chess Leonard
Published: January 2005

In patients with plasma cell dyscrasia, individual clones of antibody‐producing cells proliferate abnormally and secrete monoclonal antibodies or M proteins in excess. The cause of the monoclonal proliferation of lymphocytes and M protein secretion is unknown and it is not known whether the M protein–secreting B cells are autonomous or capable of responding to regulatory T cells. We carried out experiments using lymphocytes from a patient with neuropathy and plasma cell dyscrasia whose IgM M protein bound to the myelin‐associated glycoprotein (MAG) to determine whether secretion of the M protein in vitro was responsive to T cell help or suppression. M protein secretion was measured by an enzyme‐linked immunosorbent assay system for measuring anti‐MAG IgM, and the number of M protein–secreting lymphocytes was enumerated by a reverse hemolytic plaque assay specific for the M protein idiotype. The patient's B cells were maximally stimulated by pokeweed mitogen–activated autologous OKT4+T‐helper cells and the helper effect was inhibited by OKT8+suppressor/cytotoxic T cells. Low levels of M protein secretion in the absence of T cells were also observed and there was partial stimulation of M protein secretion by T cells in the absence of pokeweed mitogen.
Left ear suppression on verbal dichotic tests in patients with multiple sclerosis
Authors: Rubens Alan B. , Froehling Brian , Slater Gerald , Anderson David
Published: January 2005

Verbal dichotic listening tests employing nonsense consonant‐vowel stimulus pairs were administered to 11 right‐handed patients with chronic multiple sclerosis and to 10 right‐handed normal controls. A highly significant reduction of left‐ear scores was found in the multiple sclerosis group. We propose that the basis for this finding is a disconnection of the auditory callosal pathway and that dichotic listening tests may be of value in detecting the presence of lesions of the deep white matter of the cerebral hemispheres in multiple sclerosis.
Preservation of hypothalamic dopaminergic neurons in Parkinson's disease
Authors: Matzuk Martin M. , Saper Clifford B.
Published: January 2005

The integrity of the hypothalamic neuroendocrine dopaminergic neurons in Parkinson's disease was assessed by comparing the numbers and distribution of melanin‐pigmented neurons in the arcuate and periventricular nuclei in 7 parkinsonian and 5 normal brains. No significant differences were observed. In contrast to theories suggesting that Parkinson's disease involves a universal degeneration of central catecholaminergic neurons, the hypothalamic neuroendocrine dopaminergic neurons do not appear to be involved by the disease.
Corticospinal tract conduction time in multiple sclerosis
Authors: Mills Kerry R. , Murray Nicholas M. F.
Published: January 2005

Anodal shocks of 400 to 700 V from a low‐output impedance stimulator applied percutaneously over the motor cortex evoke muscle action potentials in partially voluntarily activated contralateral muscles. Cathodal shocks from the same device applied to the cervical spinal cord produce maximal ipsilateral muscle action potentials in a relaxed limb. This technique was used to study the central motor pathway in 15 healthy subjects and 8 patients with clinically definite multiple sclerosis. As stimuli were applied in the axilla, over the C7 vertebral level, and over the arm area of the motor cortex, recordings were made of muscle action potentials of forearm flexor muscles. In controls, cord‐to‐axilla conduction time was 4.1 ± 0.61 ms, and cortex‐to‐cord time was 4.4 ± 0.75 ms. In patients, cord‐to‐axilla conduction times were normal, while central conduction times were either markedly prolonged (6.4 to 31 ms) or absent. This technique is a potentially powerful tool for the investigation of central motor pathways in healthy subjects and patients with neurological disease.
Postoperative neurological deficits may occur despite unchanged intraoperative somatosensory evoked potentials
Authors: Lesser R. P. , Raudzens P. , Lüders H. , Nuwer M. R. , Goldie W. D. , Morris H. H. , Dinner D. S. , Klem G. , Hahn J. F. , Shetter A. G. , Ginsburg H. H. , Gurd A. R.
Published: January 2005

We describe 6 patients who demonstrated postoperative neurological deficits despite unchanged somatosensory evoked potentials during intraoperative monitoring. Although there is both experimental and clinical evidence that somatosensory evoked potentials are sensitive to some types of intraoperative mishap, the technique should be empolyed with an awareness of its possible limitations.
α‐1 Adrenoceptors are decreased in human epileptic foci
Authors: Brière Richard , Sherwin Allan L. , Robitaille Yvon , Olivier André , Quesney Luis F. , Reader Tomas A.
Published: January 2005

Cortical α‐1 adrenoceptors were measured in tissues obtained from 10 patients immediately following temporal lobectomy for intractable partial epilepsy. At operation each patient exhibited spontaneous spiking restricted to either the anterior (n = 5) or posterior (n = 5) portion of the first two temporal gyri. Control samples were obtained from the nonspiking half of the same gyrus. Receptor‐binding assays were performed on isolated cortical membranes using [3H]prazosin. There was a reduction (p < 0.01) in the receptor density (βmax) of the sites in the epileptic foci without any change in affinity (mean ± SEM): spiking—βmax, 160.5 ± 11.3 fmol/mg protein; affinity, 0.17 ± 0.04 nM; nonspiking—βmax, 218.8 ± 15.6 fmol/mg protein; affinity 0.17 ± 0.04 nM. This relative decrease in α‐1 adrenoceptor density may be the substratum of a noradrenergic hyposensitivity that could contribute to a localized diminution in inhibitory mechanisms in epileptic foci.
Contingent negative variation in headache
Authors: de Nordhout Alain Maertens , Timsit‐Berthier Martine , Timsit Meyer , Schoenen Jean
Published: January 2005

Contingent negative variation (CNV), an event‐related slow cerebral potential, was analyzed in 79 consecutive headache patients. Compared to normal controls (n = 33), CNV did not differ in tension headache (n = 21) or in combined headaches with a predominant tension component (n = 13). The mean amplitude of CNV was significantly (p < 0.001) increased in migraine (n = 29) as well as in combined headache with predominant migraine (n = 16). All migraineurs were studied between attacks and without prophylactic treatment. CNV may be a useful diagnostic test in headache. Its increased amplitude in migraine might reflect central catechol‐aminergic hyperactivity.
Atrial size, atrial fibrillation, and stroke
Authors: Caplan L. R. , D'Cruz I. , Hier D. B. , Reddy H. , Shah S.
Published: January 2005

M‐mode and two‐dimensional echocardiographic images were reviewed retrospectively in 20 patients with atrial fibrillation and ischemic stroke with no known valvular disease and in 20 patients with atrial fibrillation without known stroke. Left atrial size was measured and analyzed without knowledge of patient grouping. Two‐dimensional echocardiography showed that 90% of the stroke patients had left atrial enlargement compared with only 20% in the nonstroke group. This finding suggests that left atrial enlargement may convey additional stroke risk in patients with atrial fibrillation.
Cytoskeletal protein abnormalities in neurodegenerative diseases
Authors: Goldman James E. , Yen Shu‐Hui
Published: January 2005

The nervous system is a rich source of filamentous proteins that assume critical roles in determining and maintaining neuronal form and function. Neurons contain three major classes of these cytoskeletal organelles: microtubules, intermediate filaments, and microfilaments. They also contain a variety of proteins that organize them and serve to connect them with each other. Such major neurodegenerative diseases as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as a variety of toxic neuropathies, are characterized pathologically by intraneuronal filamentous inclusions. Recent studies using biochemical and immunocytochemical techniques have established that these abnormalities represent disorganized states of the neuronal cytoskeleton and have determined some of the specific molecular constituents of these inclusions. This knowledge has led to new ways of thinking about their origins.
Deficits in orofacial sensorimotor function in Parkinson's disease
Authors: Schneider Jay S. , Diamond Shirley G. , Markham Charles H.
Published: January 2005

Orofacial sensorimotor function was assessed in patients with Parkinson's disease and in age‐matched controls. Tests were designed to assess sensory function, motor abilities, and the integration of sensory information for the performance of specific movements. Patients with Parkinson's disease and normal subjects both made more errors with increasing age; however, overall, patients with Parkinson's disease made significantly more errors in our tests than did normal subjects. Interestingly, patients with Parkinson's disease showed greater deficits in tests of sensory function and sensorimotor integration than in tests of motor function. These results suggest that one aspect of Parkinson's disease consists of complex deficits in the utilization of specific sensory inputs to organize and guide movements. The results are further discussed in relation to a proposed sensory gating or filtering schema of basal ganglia motor functioning.
Thymosin β4 is a shared antigen between lymphoid cells and oligodendrocytes of normal human brain
Authors: Dalakas Marinos C. , Trapp Bruce D.
Published: January 2005

In the normal human brain, immunoreactive thymosin β4, a well‐characterized thymic extract, was demonstrated specifically in the cell bodies and processes of a subset of interfascicular and satellite oligodendrocytes with their stained processes terminating around myelin sheaths. Antisera directed against two other thymic polypeptides, thymosin α1 and α7, did not react. In lymphoid tissues, thymosin β4 was present in macrophages, Langerhans' cells of the skin, and the interdigitating cells of the thymus. Thus, a subset of oligodendrocytes shares a common antigen of thymic origin with the reticular–dendritic and phagocytic lymphoid cells—all Ia+ immunocompetent cells that participate in the presentation of antigens to T cells. The subset of thymosin β4‐positive oligodendrocytes is antigenically distinct and may play a role in the immune surveillance of the central nervous system or the demyelinating processes induced by antigen‐presenting activated macrophages.
Epidemiology of clinically diagnosed Alzheimer's disease
Authors: Rocca Walter A. , Amaducci Luigi A. , Schoenberg Bruce S.
Published: January 2005

This report reviews the current status of descriptive and analytic epidemiology of clinically diagnosed Alzheimer's disease (AD). Since AD can be diagnosed with certainty only at autopsy, currently available epidemiological data are based on a presumed clinical diagnosis. Current data indicate that AD represents a major health problem, at least in the developed countries. The prevalence ratio for AD ranges between 1.9 and 5.8 cases per 100 population aged 65 and over. Moreover, its prevalence is likely to increase in the next twenty years as a consequence of current demographic trends. The prevalence ratio for AD increases steeply with age and is higher in females. Incidence rates show a similar pattern, suggesting that AD should not be subdivided in a presenile and a senile form based on age of onset alone. Annual incidence rates of 2.4 cases per 100,000 population between ages 40 and 60, and 127 cases per 100,000 population after age 60 have been reported. Several case‐control studies show that the occurrence of either dementia or Down's syndrome in other family members, advanced age of the mother at subject's birth, and head injury are possible risk factors.
Edrophonium: An aid in the diagnosis of acute organophosphate poisoning
Authors: Maselli Ricardo , Jacobsen John H. , Spire Jean‐Paul
Published: January 2005

Unsuspected accidental cutaneous exposure to an organophosphate insecticide caused flaccid paralysis in a 10‐year‐old girl. Electromyogram demonstrated repetitive compound muscle action potentials in response to a single stimulus of nerve; decremental response, more prominent at higher rates of stimulation; worsening of decremental response after edrophonium injection; and normal nerve conduction velocities. Electromyogram with repetitive nerve stimulation and an edrophonium test may provide a simple and rapid method for diagnosis of acute organophosphate poisoning.
Neurophysiological techniques as an aid to surgical treatment of primary brain tumors
Authors: Morris Harold H. , Lüders Hans , Hahn Joseph F. , Lesser Ronald P. , Dinner Dudley S. , Estes Melinda L.
Published: January 2005

We describe a method of cortical stimulation for localizing functional area of brain before operation for primary brain tumors that was carried out in 14 patients. The method is unique in that the stimulation is done over several days using chronically indwelling subdural electrode arrays. In addition to cortical stimulation findings, somatosensory evoked potentials were helpful in locating the sensorimotor strip. The neurophysiological data have allowed an aggressive neurosurgical attack without producing a functional deficit.
Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation
Authors: Groothuis Dennis R. , Mikhael Michael A.
Published: January 2005

In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune‐complex–mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.
Cerebrospinal fluid pharmacokinetics of intrathecal morphine sulfate and D‐Ala2‐D‐Leu5‐enkephalin
Authors: Moulin Dwight E. , Inturrisi Charles E. , Foley Kathleen M.
Published: January 2005

Using an implantable pump system to deliver drugs and sample cerebrospinal fluid (CSF), we assessed rostral redistribution and systemic uptake after intrathecal bolus injection and steady‐state infusion of morphine sulfate and the opioid peptide D‐Ala2‐D‐Leu5‐enkephalin (DADL) in two patients. Following bolus injection, the mean CSF elimination half‐lives for morphine sulfate and DADL were 94 and 115 minutes, respectively. With the catheter tip at L2, the ratio of lumbar to cisternal (L/C) concentrations of morphine sulfate was about 7:1, and with the catheter tip at T10, the L/C ratios of morphine sulfate and DADL were approximately 2:1, indicating that this ratio is dependent in part on the level of intrathecal drug administration. CSF levels of morphine sulfate at steady state were three orders of magnitude higher than those in plasma. The CSF pharmacokinetics of morphine sulfate and DADL are similar, with supraspinal redistribution of these opioids via the CSF likely playing an important role in the generation of analgesia and central nervous system side effects.
Type 2 and type 3 Gaucher disease: A morphological and biochemical study
Authors: Kaye Edward M. , Ullman M. David , Wilson Edward R. , Barranger John A.
Published: January 2005

Glucocerebroside levels were measured in the brains of patients with neuronopathic forms (types 2 and 3) of Gaucher disease and compared to those obtained from control brain. Nine separate brain regions (frontal, temporal, occipital, and cerebellar cortices; thalamus; corpus striatum; pons; medulla; and dentate nuclei) were analyzed. In all the Gaucher brains studied, the greatest glucocerebroside accumulation occurred within the occipital cortex, with lesser amounts in the temporal and frontal areas. The cerebellar cortex, corpus striatum, and thalamus in Gaucher brains had mildly increased levels of glucocerebroside, especially when the values were expressed as a percentage of total nonhydroxy fatty‐acid cerebroside. Brainstem structures (pons and medulla) and dentate nuclei did not have increased glucocerebroside levels when compared to levels from similar control areas. However, when glucocerebroside concentration was expressed as a percentage of total non‐hydroxy fatty‐acid cerebroside, the type 2 Gaucher brainstem structures did show a slight increase in glucocerebroside levels over control levels. Neuropathological studies demonstrated the presence of Gaucher cells, gliosis, and microglial nodules within the type 2 brains. The neuropathological findings correlated with the glucocerebroside accumulation in the type 2 brains. Despite the similar pattern of glucocerebroside accumulation in the type 3 brain, no neuropathological abnormalities were seen. Thus, this study demonstrated that within several brain regions, both neuronopathic forms of Gaucher disease have elevated glucocerebroside levels, and that in the type 2 brains, the glucocerebroside accumulation correlated positively with the neuropathological findings.
Glial bundle formation in spinal roots following experimental neuronopathy
Authors: Yamamoto Teiji , Iwasaki Yuzo , Konno Hidehiko , Kudo Hiroko
Published: January 2005

Spinal motor neurons and dorsal root ganglion cells were caused to degenerate by axoplasmic transport of toxic lectins via the sciatic nerve. Within a few months, loss of axons and glial bundle formation were seen in the proximal portions of the L4–6 ventral and dorsal roots. The glial bundles observed were structurally the same as those described in humans, but they were occasionally also invested with Schwann cell cytoplasmic processes, the cell membrane of which was directly apposed to that of astrocytes. Basal lamina surrounding the outer surface of the bundles was shared by these two as a continuous sheet. This unique complex of astroglial and Schwann cell processes, completely covered by basal lamina, may be a newly formed interface between the central and peripheral nervous systems and thus may serve as a guide and potential pathway for regenerating neurites.
Nerve growth factor and Alzheimer's disease
Authors: Hefti Franz , Weiner William J.
Published: January 2005

Alzheimer's disease is associated with a pronounced loss of the cholinergic neurons that form the ascending cholinergic projections of the basal forebrain. Even though the disease is also characterized by changes in other neuronal systems and by a high frequency of neuronal plaques and tangles, the cholinergic deficit seems to be a principal element responsible for the memory loss typical of Alzheimer's disease. This review summarizes findings in experimental animals which indicate that nerve growth factor (NGF), a well‐characterized protein, acts as a neurotrophic factor for cholinergic neurons of the basal forebrain. NGF is present in the target areas of these cholinergic neurons and affects their survival, fiber growth, and expression of transmitter‐specific enzymes. Furthermore, NGF is able to prevent the degeneration of cholineric neurons in adult rats with experimental lesions mimicking the cholinergic deficit in Alzheimer's disease. These findings suggest that increasing the availability of NGF to human cholinergic cells might promote their survival in certain disease processes. Additional steps are discussed for establishing the possible involvement of NGF in the pathogenesis of Alzheimer's disease and the development of an effective therapy.
Contrapulsion of saccades and ipsilateral ataxia: A unilateral disorder of the rostral cerebellum
Authors: Ranalli Paul J. , Sharpe James A.
Published: January 2005

Contralateral pulsion of saccades and ipsilateral limb ataxia were manifestations of unilateral damage to the rostral cerebellum studied in a patient with occlusion of one superior cerebellar artery. The saccadic disorder consisted of three elements: (1) horizontal saccades away from the lesion during attempted vertical saccades, resulting in oblique trajectories; (2) hypermetria of contralateral saccades; and (3) hypometria of ipsilateral saccades. Magnetic search coil oculography showed that durations of the horizontal components of oblique contrapulsive saccades were lengthened toward the durations of the vertical components. Lengthening of horizontal vectors indicated temporal coupling of the orthogonal components, as occurs in normal oblique saccades. The bias of saccades arose proximal to brainstem loci that decompose commands for oblique saccades into their horizontal and vertical vectors. Contrapulsion of saccades may be explained by imbalanced cerebellar outflow.
Electrographic status epilepticus in fatal anoxic coma
Authors: Simon Roger P. , Aminoff Michael J.
Published: January 2005

Electrographic status epilepticus in the absence of conspicuous somatic motor manifestations is described in 10 patients who were comatose following anoxic–ischemic brain damage. The outcome was unfavorable and the response to anticonvulsant drugs was poor. We describe a clinical sign predictive of the electroencephalographic findings, namely brisk, small‐amplitude, mainly vertical eye movements readily detectable by passively elevating the lids. However, similar eye movements may infrequently be found in patients whose electroencephalograms show abnormal spike discharges without the occurrence of electrographic status epilepticus following cerebral anoxia, as in 2 other patients we describe.
Locus ceruleus lesions and eosinophilic inclusions in MPTP‐treated monkeys
Authors: Forno Lysia S. , Langston J. William , DeLanney Louis E. , Irwin Ian , Ricaurte George A.
Published: January 2005

Systemic administration of the recently discovered neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) produces severe clinical parkinsonism and degeneration of the substantia nigra in humans and monkeys. In previous studies, no convincing structural damage to nerve cells outside the substantia nigra could be demonstrated in subhuman primates. Using a protracted MPTP regimen and older animals, we now report locus ceruleus lesions and eosinophilic inclusion bodies in squirrel monkeys. The inclusions were seen only in areas where Lewy bodies are found in human Parkinson's disease. No such abnormalities were seen in control animals. These findings suggest that similarities between the neuropathology of MPTP‐induced parkinsonism in the monkey and human Parkinson's disease are greater than first thought and increase the usefulness of the MPTP monkey model for research in Parkinson's disease.
Proton magnetic resonance imaging in ischemic cerebrovascular disease
Authors: Salgado Efrain D. , Weinstein Meredith , Furlan Anthony J. , Modic Michael T. , Beck Gerald J. , Estes Melinda , Awad Issam , Little John R.
Published: January 2005

Proton magnetic resonance imaging (MRI) using a 0.6‐ or 1.5‐Tesla superconductive magnet was compared with high‐resolution computed tomography (CT) in 60 patients with transient ischemic attacks (TIAs) or brain infarction. MRI showed focal parenchymal changes in 84% of patients with TIAs, whereas CT showed similar changes in 42%. The sensitivity of MRI was also greater in patients with infarcts, but the difference between CT and MRI was not as great. Infarcts were usually better delineated by MRI regardless of location. However, MRI failed to reveal cortical infarcts that were clearly seen on contrast‐enhanced CT scans and was unable to clearly distinguish subacute from chronic hemorrhagic infarcts. MRI changes were best detected with T2‐weighted images and usually appeared as multiple areas of increased signal intensity in the subcortical and periventricular white matter. MRI changes often could not be correlated with the clinical history and neurological findings; identical changes have been seen in patients with no history of cerebrovascular disease.
Dendritic atrophy in children with Down's syndrome
Authors: Becker L. E. , Armstrong D. L. , Chan F.
Published: January 2005

Dendritic branching was evaluated in the visual cortex of 8 children with Down's syndrome and 10 controls, ranging in age from 4 months to 7 years and divided into infantile, late‐infantile, and juvenile groups. Camera lucida drawings of Golgi‐impregnated neurons were used for examining the following dendritic aspects: dendritic intersections as a function of distance from the cell body, point of maximum dendritic branching, number of branch orders, total number of branch segments, and total dendritic length. The number of intersections and the total dendritic length were above normal in the infantile period (6 months old or less) and dropped steadily to significantly below normal in the juvenile group (older than 2 years). These reductions contrasted with expanding dendritic arborization in normal children. The results suggest that the dendritic tree atophies in early childhood in Down's syndrome.
Gerstmann‐Sträussler‐Scheinker disease: Autopsy study of a familial case
Authors: Vinters Harry V. , Hudson Arthur J. , Kaufmann John C. E.
Published: January 2005

Postmortem neuropathological findings in a patient with biopsy‐proved familial Gerstmann‐Sträussler‐Scheinker disease of eight years' duration included severe spongy change in the neocortex, extensive and often large amyloid deposits throughout the cerebral hemispheres and cerebellum, and severe astrocytic gliosis throughout all areas of gray and white matter within the brain. The degree of cortical spongy change was much greater than that in relatives who died with a similar clinical history, indicating the phenotypic heterogeneity in this familial disorder.
Neuropeptides in neurological disease
Authors: Beal M. Flint , Martin Joseph B.
Published: January 2005

Neuropeptides are widely distributed in the central nervous system, where they serve as neuroregulators. Recent interest has focused on their role in degenerative neurological diseases. We describe the normal anatomy of neuropeptides in both the cerebral cortex and basal ganglia as a framework for interpreting neuropeptide alterations in Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease. Concentrations of cortical somatostatin are reduced in AD and in dementia associated with Parkinson's disease. Concentrations of neuropeptide Y and corticotropin‐releasing factor are also reduced in AD cerebral cortex. The reduced cortical concentrations of somatostatin and neuropeptide Y in AD cerebral cortex may reflect a loss of neurons or terminals in which these two peptides are colocalized. In Huntington's disease, basal ganglia neurons in which somatostatin and neuropeptide Y are co‐localized are selectively preserved. Cerebrospinal fluid concentrations of neuropeptides in AD reflect alterations in cortical concentrations. Improved understanding of neuropeptides in degenerative neurological illnesses will help define which neuronal populations are specifically vulnerable to the pathological processes, and this could lead to improved therapy.
Transfection of human skeletal muscle cells with SV40 large T antigen gene coupled to a metallothionein promoter
Authors: Hurko Orest , McKee Linda , Zuurveld Judith G. E. M.
Published: January 2005

We have undertaken to increase the proliferative capacity of cultured human skeletal myocytes by transfection with a plasmid construct that contains the immortalizing and transforming large T antigen gene of simian virus 40 (SV40) under the control of a zinc‐sensitive metallothionein promoter. This construct was chosen to permit rapid growth of transformants in zinc‐containing medium, which induces high levels of T antigen expression, and muscle‐specific differentiation after withdrawal of exogenous zinc, which reduces levels of T antigen. When grown in 100 μM Zn2+, transformed myocytes expressed the large T antigen, divided rapidly, and acquired an apparently unlimited proliferative capacity. Transfer of these cells to a zinc‐poor medium resulted in decreased T antigen immunofluorescence, growth rate, and saturation density as well as a return to a physiological spindle morphology. Despite transformation, these cells expressed differentiation markers characteristic of myoblasts: the B isoform of creatine kinase, and surface antigens 5.1H11, D5, and Thy 1 in the presence or absence of Zn2+. When grown to high density in a serum‐poor medium, these cells differentiated further into typical multinucleated myotubes that expressed the M isoform of creatine kinase and increased levels of surface antigen 5.1H11, creatine kinase, and nicotinic acetylcholine receptors, but no detectable Thy 1 antigen. The specific activity of these differentiation markers was higher when the cells were grown in the absence of added zinc. These results indicate that transformation of human skeletal myocytes with a regulatable SV40 large T antigen gene allows an increase of the proliferative capacity of these cells with preservation of their capacity to differentiate in a physiological manner.
Schwannoma presenting as lumbar disc disease in an adolescent boy
Authors: Lahat Eliezer , Rothman Allen S. , Aron Alan M.
Published: January 2005

Lumbar disc disease and spinal cord tumors occur relatively rarely in the pediatric age group. We report on a 16‐year‐old boy who presented with signs and symptoms of lumbar disc disease that failed to respond to conservative treatment. He was diagnosed preoperatively to have schwannoma of the S‐1 root.
Left thalamic infarction and disturbance of verbal memory: A clinicoanatomical study with a new method of computed tomographc stereotaxic lesion localization
Authors: Mori Etsuro , Yamadori Atsushi , Mitani Yohko
Published: January 2005

A 41‐year‐old right‐handed man developed disturbances of language and memory after a discrete thalamic infarction. Detailed neuropsychological assessment revealed deficits in verbal fluency, word finding, confrontation naming, and anterograde memory for verbal material. High‐resolution computed tomography with stereotaxic lesion localization permitted the determination of the thalamic nuclei involved in the infarction. We suggest that the patient's problem in language and verbal memory reflected a defect in memory processing for verbal material during registration, retention, and retrieval, and that this defect probably resulted from a left anterior thalamic lesion affecting the ventrolateral nucleus, centromedian‐parafascicular nuclei complex, internal medullary lamina, or mamillothalamic tract.
Sickle cell anemia and central nervous system infarction: A neuropathological study
Authors: Rothman Steven M. , Fulling Keith H. , Nelson James S.
Published: January 2005

CNS infarcts were demonstrated in 12 of 24 autopsied patients with sickle cell anemia. The infarcts occurred most extensively in the territory supplied by the distal branches of the internal carotid artery, especially the anterior–middle cerebral artery boundary zone. They were regularly associated with organizing and recanalizing thrombi involving the distal cervical and proximal intracranial divisions of the internal carotid system. On the basis of these findings, we infer that the pathogenesis of the infarction involves perfusion failure or intraarterial embolization in addition to intravascular sickling.
Structural determinants of electroencephalographic findings in acute hemispheric lesions
Authors: Schaul Neil , Green Lawrence , Peyster Robert , Gotman Jean
Published: January 2005

We studied electroencephalograms and computed tomographic scans of 54 patients with acute hemispheric strokes. Electrographic parameters evaluated included field, amplitude, frequency, persistence, and reactivity of focal or lateralized slow‐wave activity. Ipsilateral and contralateral background activity were also assessed. Structural and clinical features studied were lesion size, density, mass effect, location, tissue involvement, deep structure involvement, level of consciousness, and outcome. The data were analyzed using computer sorting and the χ2 test. The field, amplitude, and frequency of focal slow‐wave abnormalities generally failed to show a specific association with structural details. Continuous focal abnormalities correlated with large lesions (p < 0.05), mass effect (p < 0.05), and altered state of consciousness (p < 0.05). Reactive focal abnormalities were associated with small lesions (p < 0.05) and the absence of mass effect (p < 0.02). Ipsilateral background activity abnormalities correlated with lesion size (p < 0.001) and mass effect (p < 0.01). Attenuation of ipsilateral background activity was more important than irregularity. Abnormal background activity contralateral to the lesion side was associated with alteration of consciousness (p < 0.05).
The pathophysiology of penicillamine‐induced myasthenia gravis
Authors: Kuncl Ralph W. , Pestronk Alan , Drachman Daniel B. , Rechthand Emanuel
Published: January 2005

The temporal course and pathophysiology of penicillamine‐induced myasthenia gravis were studied in detail in a typical case. Our results suggest that this disorder and idiopathic autoimmune myasthenia gravis share the same essential pathophysiological features, including the presence of anti–acetylcholine receptor (AChR) antibody, serum‐induced blockade of AChRs, antibody‐mediated accelerated degradation of AChRs, and a resultant quantitative reduction in available junctional AChRs. An initial severe reduction in junctional AChRs was reversed and the patient recovered, both within 8 months of stopping penicillamine. Our data suggest that penicillamine probably produced myasthenia gravis by initiating a new autoimmune response rather than by enhancing ongoing autoimmunity.