bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of encephalitis in children: A 20‐Year survey
Authors: Koskiniemi Marjaleena , Rautonen Jukka , Lehtokoski‐Lehtiniemi Eeva , Vaheri Antti
Published: January 2005

Four hundred five children from the Helsinki area who were 1 month to 16 years old were treated for acute encephalitis at the Children's Hospital, University of Helsinki, from January 1968 through December 1987. Encephalitis occurred most commonly in children 1 to 1.9 years of age, among whom the incidence was 16.7 per 100,000 child‐years. The incidence remained quite high until the age of 10 years, and then gradually declined to 1.0 per 100,000 child‐years at the age of 15 years. Since 1983, when mumps, measles, and rubella vaccination eradicated the encephalitides associated with these microbes, the major associated agents have been varicella‐zoster, Mycoplasma pneumoniae, and respiratory and enteroviruses. In infants younger than 1 year of age, the major agents were enteroviruses, herpes simplex virus, and the group of “others,” whereas in older children, respiratory viruses and Mycoplasma Pneumoniae as well as varicella‐zoster virus, dominated. In children aged 1 to 11 months, the causal agent could not be identified in one‐half of all cases, whereas in children who were at least 10 years old, the etiology remained unknown in only one‐fourth of cases. Male dominance was most evident in the 4‐ to 9‐year age group. The difference in etiology between males and females was significant (p = 0.02); mumps and varicella were more common in boys, and adenovirus and Mycoplasma pneumoniae were more common in girls. The overall male‐to‐female ratio was 1.4:1. Characteristic seasonal variation occurred in encephalitides associated with mumps, measles, and entero‐ and respiratory viruses. In the whole series, some accumulation appeared in February and March. Less than one‐half of this number appeared in July and August.
Serial gadolinium‐enhanced magnetic resonance imaging scans in patients with early, relapsing‐remitting multiple sclerosis: Implications for clinical trials and natural history
Authors: Harris Jonathan O. , Frank Joseph A. , Patronas Nicholas , McFarlin Dale E. , McFarland Henry F.
Published: January 2005

Six patients with early, mild, relapsing‐remitting multiple sclerosis were studied with monthly gadolinium‐enhanced magnetic resonance imaging scans for 8 to 11 months. Numerous enhancing lesions were observed irrespective of clinical activity. Four of the 6 patients had one or more enhancing lesions present on each examination. The other 2 patients had enhancing lesions noted in 7 and 9 of 11 months. In contrast, only two clinical exacerbations were observed during the study period. Neither the exacerbations nor other changes in symptoms or signs correlated with occurrence of the enhancing lesions. Enhancement generally persisted for less than 1 month. The opening of the blood‐brain barrier as reflected by gadolinium enhancement on magnetic resonance imaging may represent ongoing disease activity in patients with mild, relapsing‐remitting multiple sclerosis who are clinically stable. The frequency of these lesions appears to be sufficient to use as an outcome measure in clinical trials testing clinical efficacy in patients with early, relapsing‐remitting multiple sclerosis.
Central sleep apnea and arterial compression of the medulla
Authors: Miyazaki Masahito , Hashimoto Toshiaki , Sakurama Noriko , Yoshimoto Tsutomu , Tayama Masanobu , Kuroda Yasuhiro
Published: January 2005

We report a 5‐year‐old with central sleep apnea associated with compression of the medulla oblongata by abnormal looping of the left vertebral artery. The magnetic resonance imaging findings raise the possibility that compression of the respiratory center by an aberrant vertebral artery might cause central sleep apnea.
Epileptiform electroencephalographic abnormalities in liver transplant recipients
Authors: Wszolek Z. K. , Aksamit A. J. , Ellingson R. J. , Sharbrough F. W. , Westmoreland B. F. , Pfeiffer R. F. , Steg R. E. , De Groen P. C.
Published: January 2005

We retrospectively studied patients who had undergone orthotopic liver transplantation and who also had electroencephalography to determine whether epileptiform changes were associated with a poor neurological outcome. Study groups were 36 patients who died after transplantation (141 electroencephalograms) and underwent neuropathological examination, 11 who died (18 electroencephalograms) but did not have autopsy, and a third group of 34 (62 electroencephalograms) who remained alive. Epileptiform activity was seen in electroencephalograms of 14 of the patients who died (11 from the autopsy group) and in 2 of those who remained alive. All had multiple epileptiform abnormalities and clinical or subclinical seizures. The incidence of epileptiform activity after orthotopic liver transplantation was fivefold higher in the nonsurvivors. Serious cerebral structural changes were found in 10 of the 11 patients who underwent autopsy. Epileptiform activity in the electroencephalograms of patients who had undergone orthotopic liver transplantation indicates a poor prognosis. It should alert the clinician to investigate further for potentially treatable causes.
Calcium channel antagonists and human immunodeficiency virus coat protein–mediated neuronal injury
Authors: Lipton Stuart A.
Published: January 2005

Recent evidence in vitro has suggested that neuronal injury observed in the acquired immunodeficiency syndrome dementia complex may depend, at least in part, on toxic effects of the human immunodeficiency virus type 1 envelope protein, gp120. This laboratory previously reported that members of the dihydropyridine class of calcium channel antagonists, nimodipine and nifedipine, greatly attenuate the rise in intracellular calcium engendered by gp120 and prevent subsequent neuronal injury. The relatively low (nanomolar) concentrations of dihydropyridines that were effective suggested that their action might be exerted at the level of the L‐type of voltage‐dependent calcium channels. In the present study, I tested members of the three other major classes of Ca2+ channel antagonist drugs to determine if they too could prevent neurotoxicity induced by gp120. At the maximal dose that did not cause neuronal damage in and of itself, a diphenylalkylamine piperazine derivative (flunarizine, 10 μM) was the most effective, a phenylalkylamine (verapamil, 100 μM) was possibly effective, whereas a benzothiazepine (diltiazem, 1 μM) was ineffectual in protecting rat retinal ganglion cells from gp120‐induced toxicity in vitro. To explain these results, previous work has shown that the various classes of Ca2+ channel antagonists may exhibit differential potency in blocking voltage‐dependent Ca2+ current in neurons, with dihydropyridines and flunarizine being the most potent at neuronal calcium channels. Moreover, these channels on mammalian central neurons are relatively insensitive to agents such as verapamil and diltiazem compared with other cell types like muscle. The low micromolar concentrations necessary for potency of flunarizine is in keeping with that predicted by binding and electrophysiological studies for block of voltage‐dependent calcium channels. Other mechanisms of neuroprotection by flunarizine from gp120, however, cannot be totally excluded.
Ocular motor abnormalities in human immunodeficiency virus infection
Authors: Merrill Pauline T. , Paige Gary D. , Abrams Richard A. , Jacoby Robert G. , Clifford David B.
Published: January 2005

We studied ocular motor performance in 47 subjects with human immunodeficiency virus (HIV) infection and 25 normal control subjects. Saccade accuracy was the most sensitive measure, being significantly poorer for all four HIV‐positive groups (asymptomatic, acquired immunodeficiency syndrome [AIDS] without dementia, and AIDS with dementia, and AIDS‐related complex) than for control subjects. While saccade duration and peak velocity were not significantly different across groups, the scatter of saccade duration was increased in all HIV‐positive groups. Saccade latency was not significantly affected. In both simple and complex antisaccade tasks, the asymptomatic, AIDS, and AIDS dementia groups made significantly fewer correct‐way antisaccades than did control subjects. Latencies of correct‐way antisaccades were increased for the AIDS and AIDS dementia groups in the simple antisaccade trials, and for all HIV‐positive groups in the complex trials. Fixation stability was significantly worse in the AIDS dementia group than in control subjects. Smooth pursuit gain was Decemberreased in the asymptomatic, AIDS, and AIDS dementia groups for the least demanding trial. One or more ocular motor abnormalities were present in 15 (88%) asymptomatic subjects, 11 (69%) with AIDS‐related complex, and 14 (100%) AIDS patients without or with dementia.
Focal neuronal migration disorders and intractable partial epilepsy: A study of 30 patients
Authors: Palmini André , Andermann Frederick , Olivier André , Tampieri Donatella , Robitaille Yvon , Andermann Eva , Wright Geoffrey
Published: January 2005

We studied 30, patients with partial epilepsy and a radiological or pathological diagnosis of localized neuronal migration disorders, with a view to surgical treatment. Eight patients had identifiable prenatal etiological factors. The frequency of complex partial, partial motor, and secondarily generalized seizures was approximately 70° each. Drop attacks were present in 27°: Their presence usually correlated with a lesion involving the central region. Partial motor or generalized convulsive status epilepticus occurred in 30°, and was most frequently associated with extensive structural abnormalities involving two or more lobes. A full‐scale intelligence quotient of less than 80 was found in 44°. Magnetic resonance imaging (MRI) was superior to computed tomography for identification of the dysplastic cortical lesions. In one third, MRI showed only subcortical abnormalities. It did not allow distinction between true pachygyria, focal cortical dysplasia, or the forme fruste of tuberous sclerosis. The epileptogenic area was usually more extensive than the lesion; it was multilobar in more than 70° of patients. Of 26 surgically treated patients, a histological diagnosis of the type of neuronal migration disorder was possible in 22:12 had focal cortical dysplasia and 10 the forme fruste of tuberous sclerosis. In the remaining 4, no definite histological diagnosis was made, since the maximally abnormal tissue could not be examined. In the latter, and in the 4 nonoperated patients, the diagnosis of neuronal migration disorder was based on imaging findings. The presence of the forme fruste of tuberous sclerosis correlated with delayed psychomotor development and more extensive epileptogenic areas.
Peripheral blood γ‐δ T cells lyse fresh human brain—Derived oligodendrocytes
Authors: Freedman Mark S. , Ruijs Theodora C. G. , Selin Liisa K. , Antel Jack P.
Published: January 2005

T cells are postulated to contribute to the injury of the oligodendrocyte‐myelin complex underlying the demyelinating disease multiple sclerosis (MS). The apparent lack of class I or II major histocompatibility complex (MHC) expression in situ on human oligodendrocytes and the consistent failure to identify a universal myelin antigen in MS suggest that the immune damage might be mediated by effector T cells that are capable of reacting in an antigen‐nonspecific and possibly MHC‐unrestricted manner, such as T cells expressing the γ‐δ T‐cell receptor. Since γ‐δ T cells are reported to be present in MS plaques and an increased number are found in the cerebrospinal fluid of patients with MS, we directly examined whether γ‐δ T cells are capable of inducing injury to human oligodendrocytes. We found, using a 6‐hour 51Cr release assay, that oligodendrocytes cultured from surgically resected human brain specimens were effectively lysed in a dose‐dependent manner by human γ‐δ T Cells (28 ± 5% mean specific lysis, n = 6, at an effector‐target ratio of 20:1). Although heat shock protein HSP72, a putative γ‐δ T‐cell recognition molecule, could be induced in vitro in our oligodendrocytes, an antibody to HSP72 did not inhibit γ‐δ T cell‐mediated lysis of oligodendrocytes. These results suggest that γ‐δ T cells gaining entry into the central nervous system may be deleterious to oligodendrocytes and thus may contribute to the pathogenesis of MS.
Focal conduction block in the dorsal root ganglion in experimental allergic neuritis
Authors: Stanley Glenn P. , McCombe Pamela A. , Pender Michael P.
Published: January 2005

Acute experimental allergic neuritis was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. In terminal experiments, sensory conduction was assessed in rats with hindlimb ataxia and weakness by stimulating the exposed sciatic nerve and recording directly from the exposed L‐4 spinal nerve, dorsal root ganglion, dorsal root, and dorsal root entry zone. Focal conduction block was present in a high proportion of large‐diameter fibers in the dorsal root ganglion. In contrast, nerve conduction in the peripheral nerve and spinal nerve was essentially normal apart from probable conduction block in some fibers in the proximal spinal nerve in a minority of rats. The afferent volley arriving at the dorsal root entry zone of the spinal cord was greatly reduced, as a consequence of the conduction block in the dorsal root ganglion and probable conduction block in the dorsal root. The M wave recorded from the fourth dorsal interosseus muscle of the hindfoot was normal in amplitude but slightly prolonged in latency and the H reflex was absent. These electrophysiological findings correlated well with the histological findings of inflammation and prominent demyelination in the dorsal root ganglia and dorsal roots with minimal involvement of the proximal spinal nerve and no involvement of the sciatic nerve. It is concluded that the hindlimb ataxia in rats with this form of acute experimental allergic neuritis is due to demyelination‐induced nerve conduction block in the dorsal root ganglia and probably in the dorsal roots.
Cytochrome C oxidase deficiency and Long‐Chain acyl coenzyme A dehydrogenase deficiency with Leigh's subacute necrotizing encephalomyelopathy
Authors: Reichmann Heinz , Scheel Helmut , Bier Bert , Ketelsen Uwe‐Peter , Zabransky Siegfried
Published: January 2005

A female infant was seen at the age of 2 months because of hypotonia, delayed motor development, and lactic acidosis, and she died at age 13 months due to respiratory failure. In a muscle specimen taken at 11 months and in a liver specimen obtained 1.5 hours postmortem, we found decreased activities of cytochrome c oxidase and longchain acyl coenzyme A dehydrogenase. Neuropathological changes were typical for Leigh's subacute necrotizing encephalomyelopathy. To our knowledge, this is the first report of a combined defect of complex IV of the respiratory chain and of the long‐chain specific acyl coenzyme A dehydrogenase of β‐oxidation in muscle and liver.
Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C‐raclopride and positron emission tomography
Authors: Brooks D. J. , Ibanez V. , Sawle G. V. , Playford E. D. , Quinn N. , Mathias C. J. , Lees A. J. , Marsden C. D. , Bannister R. , Frackowiak R. S. J.
Published: January 2005

Equilibrium striatal: cerebellar 11C‐raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L‐dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean strital: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and fluctuating response to L‐dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L‐dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment. Failure of patients with SND and PSP to respond well to L‐dopa cannot therefore be due to losss of striatal D2 sites alone, but must reflect loss of other basal ganglia connections.
Congenital hypomyelination neuropathy with arthrogryposis multiplex congenita
Authors: Boylan Kevin B. , Ferriero Donna M. , Greco Claudia M. , Sheldon R. Ann , Dew Michael
Published: January 2005

A term male infant is described with an isolated disorder of peripheral myelination. At necropsy, the great majority of medium‐to‐large axons were unmyelinated. Electron microscopy showed normal axons and redundant lamination of basement membrane, suggestive of early onion bulb pathology. Immunohistochemistry of peripheral nerve showed deficiency of the myelin proteins P2 and Po, myelin basic protein, and myelin‐associated glycoprotein. Arrest of peripheral myelination at the promyelin stage appears to be the origin of myelin deficiency.
Distribution of cisternal blood in patients with acute hydrocephalus after subarachnoid hemorrhage
Authors: Hasan Djo , Tanghe Hervé L. J.
Published: January 2005

The distribution of cisternal blood in relation to the development of acute hydrocephalus was studied in 246 consecutive patients with aneurysmal subarachnoid hemorrhage who were admitted within 72 hours. Patients with evidence on the initial computed tomograph (CT) of subarachnoid hemorrhage caused by other than a ruptured aneurysm and patients with a negative angiography were excluded. Acute hydrocephalus (defined as a bicaudate index, measured on the initial CT or on a repeat CT within 1 week after subarachnoid hemorrhage, exceeding the 95th percentile for age) was found on the initial CT in 50 (20%) of the 246 patients and on a repeat CT in 9 other patients. Ventricular blood was found significantly more often in patients with acute hydrocephalus than in those in whom acute hydrocephalus did not develop (28 of 59 {47%} versus 58 of 187 {31%}; χ2 = 4.634, p = 0.031). When the analysis was restricted to the 86 patients with ventricular blood, no significant differences were found in the total amount of cisternal blood and in the distribution of cisternal blood between patients with and without hydrocephalus. In contrast, among the 160 patients with ventricular blood, hydrocephalus was associated with a slightly higher total amount of cisternal blood (Wilcoxon's rank sum test, p = 0.023), and significantly more patients with acute hydrocephalus had a higher score in both ambient cisterns than patients without acute hydrocephalus (20 of 31 {65%} versus 41 of 129 {32%}; χ2 = 10.007, p = 0.002). We conclude that the risk of acute hydrocephalus developing in patients without ventricular blood following rupured aneurysm is significantly increased in those with a high cisternal score for blood in both ambient cisterns.
Voluntary activation and fiber density of fasciculations in motor neuron disease
Authors: Guiloff Roberto J. , Modarres‐Sadeghi Hamid
Published: January 2005

Two hundred voluntarily activated motor units and 211 fasciculations were recorded in the biceps of 10 patients with motor neuron disease with the Macro EMG technique. Twenty‐two fasciculating, in nine of 10 muscles, had a potential of closely similar shape, amplitude, and area to that of a voluntary unit. Fasciculating units that could not be activated voluntarily had a higher mean number of spikes in their triggering single fiber potentials than units that could only be activated voluntarily, but statistically similar Macro EMG parameters. The mean number of single fiber spikes, and Macro EMG parameters, of fasciculations activated voluntarily, were similar to those of units that were only activated voluntarily. A positive correlation between fiber density and Macro EMG median amplitude and area in individual patients, and between number of single fiber spikes and Macro EMG amplitudes and areas in the pooled data, was found for fasciculations but not for voluntary units. At least 10% of fasciculations in patients with motor neuron disease may originate near or above the point of axonal branching and a proportion of those without evidence of voluntary activation may have a higher number of smaller muscle fibers, or more closely packed muscle fibers, of similar or greater size, than voluntarily activated motor units. Differences in the peripheral microanatomy of a number of fasciculation units not activated voluntarily may underlie ectopic impulse generation in the terminal axonal arborization, endplate zone, or muscle fibers of these units.
JC virus infection and Alzheimer's disease: Reappraisal of an in situ hybridization approach
Authors: Heinonen Outi , Syrjänen Stina , Mäntyjärvi Rauno , Syrjänen Kari , Riekkinen Paavo
Published: January 2005

To assess the validity of the recently reported data on frequent occurrence of latent JC virus (JCV) infections in the brains of patients with Alzheimer's disease, we used in situ hybridization with biotinylated whole genomic JCV probes and the streptavidin‐biotinylated alkaline phosphatase method to examine brain sections of such patients. We did not find any signs of JCV either in the brains of the patients with Alzheimer's disease or in those of nondemented, elderly control patients. Nonspecific staining of corpora amylacea–like bodies, however, was invariably detected with in situ hybridization using JCV probes.
Prognostic value of cytogenetic analysis in human cerebral astrocytomas
Authors: Kimmel David W. , O'Fallon Judith R. , Scheithauer Bernd W. , Kelly Patrick J. , Dewald Gordon W. , Jenkins Robert B.
Published: January 2005

Cytogenetic analysis has become an important part of the diagnostic evaluation of most hematological neoplasms. However, there is limited information on the value of cytogenetic analysis in most solid tumors, including cerebral astrocytomas. This report summarizes a prospective cytogenetic study of 99 human cerebral astrocytomas, 16 mixed oligoastrocytomas, and 2 gliosarcomas. The cytogenetic procedure involved in situ culture and robotic harvesting techniques. Correlative clinical and survival data were available on all patients. We successfully cultured and obtained suitable metaphases in 107 of the 117 tumors. One or more chromosomally abnormal clones were observed in 72 tumors, and nonclonal or normal karyotypes were observed in 35 tumors. In a multivariate analysis, survival time was significantly better in patients whose tumors had normal or nonclonal karyotypes on cytogenetic analyses than in those whose tumors had clonal abnormalities (p = 0.0071). Our study demonstrates that cytogenetic analysis provides independent prognostic information in patients with cerebral astrocytomas.
Recent progress toward understanding the molecular biology of von Recklinghausen neurofibromatosis
Authors: Gutmann David H. , Collins Francis S.
Published: January 2005

The gene for von Recklinghausen neurofibromatosis (NF1) was recently identified by positional cloning and found to code for a large, ubiquitously expressed protein. This protein has both structural and functional similarity to a family of proteins with guanosine triphosphatase–activating properties, involved in the regulation of the protooncogene ras. One of the postulated functions of the NF1 gene product may relate to its ability to regulate ras‐mediated cell proliferation. Selective pharmacotherapy directed at downregulating ras may be of benefit to patients with NF1.
The transcription factor Sp1 binds to the JC virus promoter and is selectively expressed in glial cells in human brain
Authors: Henson John , Saffer Jeffrey , Furneaux Henry
Published: January 2005

JC virus is a human DNA virus that specifically infects oligodendroglial cells, resulting in a demyelinating disease (progressive multifocal leukoencephalopathy) of the central nervous system of immunosuppressed patients. The hostrange restriction of JC virus is controlled at the level of viral gene transcription. To analyze further the determinants of glial specificity, we cloned and sequenced the JC viral early promoter elements directly from the infected brain tissue of four patients. The promoter of each isolate contained a novel identical sequence, 5′‐AGGGAGGAGC(GA box), located immediately upstream of the TATA box. This GA box is not present in the original isolate of JC virus (Mad‐1 strain), which was obtained after numerous passages in tissue culture. The GA box has 80% homology with the consensus binding site for the transcription factor Sp1. Using a gel retardation assay, we found that Sp1 binds to the GA box. Alteration of bases within the sequence abolished binding of Sp1, demonstrating sequence specificity of binding. Immunohistochemical localization of Sp1 expression in human brain reveals that expression is restricted to the nuclei of oligodendroglial cells, cerebellar basket cells, and endothelial cells. The GA box is present in the promoters of the myelin basic protein and proteolipid protein genes. On the basis of these observations, we suggest that this Sp1‐like binding site participates in the control of glial‐specific gene expression.
Multiple sclerosis in children: Cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo
Authors: Bruhn H. , Frahm J. , Merboldt K. D. , DiplMath W. Hänicke , Hanefeld F. , Christen H. J. , Kruse B. , Bauer H. J.
Published: January 2005

In vivo proton magnetic resonance spectroscopy of 8 children (7–16 years) with established multiple sclerosis revealed distinct alterations in regional cerebral metabolism associated with different aspects of the disease: (1) Localized proton spectra (2 to 4‐ml volumes of interest) from multiple sclerosis plaques were generally characterized by a decrease in N‐acetylaspartate and creatines, and an increase in cholines and myo‐inositol relative to age‐matched control subjects, (2) neither chronic nor enhancing plaques (by gadolinium‐diethylenetriamine pentaacetic acid) during an acute exacerbation showed elevated levels of lactate or lipids, (3) spectra from adjacent white matter that did not appear suspicious in magnetic resonance images were similar to those of normal control subjects, and (4) cortical gray matter related to neighboring multiple sclerosis lesions showed a notable reduction of N‐acetylaspartate. The present results show that functional impairment in multiple sclerosis is linked to gross metabolic disturbances of neuronal cell chemistry. We suggest that focal demyelination is accompanied by increased membrane precursors of proliferative turnover and is associated with secondary neuronal shrinkage or loss, perhaps extending into related cortical gray matter.
Subclinical histopathological changes in the oculomotor nerve in diabetes mellitus
Authors: Smith Benn E. , Dyck Peter James
Published: January 2005

To provide reference values for the oculomotor nerve, for example, fascicular area and myelinated fiber (MF) number and size distribution, in pathological states, and to determine whether oculomotor nerves from diabetic patients without a history of oculomotor palsy have subclinical structural alterations, the morphometric features of 15 control subjects and eight diabetic patients were evaluated at a proximal and a distal level. On average the control nerves had a fascicular area of 2.7 mm2, 22,311 MF, and a bimodal diameter distribution with peaks at approximately 5 to 6 and 10 to 11 μm and a range of 2 to 20 μm. In proximal nerve, glial bundles were found in one‐half of the subjects and patients, with a peak of MF sizes that differed from fibers in nonglial areas. The nerves from diabetic patients departed from the nerves from control subjects in the following two respects: changed size distribution, suggesting atrophy of fibers, and microfasciculation of edge fibers in parts of the fascicles in one‐half of the patients. We conclude that glial bundles are probably a normal variant. Microfasciculation occurred much more frequently in nerves from diabetic patients and may represent subclinical injury of unknown cause. The alteration in size distribution may reflect the diabetic state and is not necessarily a precursor to diabetic ophthalmoplegia.
Nigral damage and dopaminergic hypofunction in mesencephalon‐immunized guinea pigs
Authors: Appel Stanley H. , Le Wei‐Dong , Tajti Janos , Haverkamp Lanny J. , Engelhardt Jozsef I.
Published: January 2005

To support a potential role for immune mechanisms in the destruction of substantia nigra (SN) neurons, guinea pigs were immunized with bovine mesencephalon containing SN neurons. After immunization no clinical signs of basal ganglia dysfunction appeared. However, pathological examination revealed evidence of neuronal damage in the SN in 8 of 17 guinea pigs immunized with bovine mesencephalon. No nigral pathology was noted in animals immunized with spinal cord gray matter or Freund's adjuvant alone. Accompanying the SN damage in mesencephalon‐immunized guinea pigs was a 25% decrease in tyrosine hydroxylase activity in the SN and a 27% decrease in dopamine content in the striatum. Deposits of IgG were detected by immunohistochemical techniques in sections of SN from mesencephalon‐immunized guinea pigs and in sections of human SN after exposure to serum from mesencephalon‐immunized guinea pigs. These data document the antigenicity of SN and suggest the possibility that immune mechanisms can contribute to basal ganglia pathology.
Decrease of D2 receptors indicated by 123I‐iodobenzamide single‐photon emission computed tomography relates to neurological deficit in treated Wilson's disease
Authors: Oertel W. H. , Tatsch K. , Schwarz J. , Kraft E. , Trenkwalder C. , Scherer J. , Weinzierl M. , Vogl T. , Kirsch C. M.
Published: January 2005

Single‐photon emission computed tomography with 123I‐iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age‐matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age‐matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 ± 0.04 (mean ± standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 ± 0.05 (n = 5, asymptomatic patients) to 1.17 ± 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I‐iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM‐SPECT (correlation coefficient, −0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM‐SPECT reflects striatal neuronal damage in Wilson's disease.
The free radical hypothesis in idiopathic parkinsonism: Evidence against it
Authors: Calne Donald B.
Published: January 2005

The free radical hypothesis for the pathogenesis of idiopathic parkinsonism (Parkinson's disease) has many similarities to the argument invoking an autoimmune mechanism. In both cases, cellular and molecular machinery that might be involved in neuronal destruction have been demonstrated. In recent years, the free radical hypothesis has become particularly fashionable; several workers have reported observations which, they infer, support the notion that damage by free radicals is a major factor in the underlying disease process. There is, however, no conclusive evidence that free radicals play a prominent role in the causal chain of events that leads to idiopathic parkinsonism; several findings may be construed as evidence against such a contention.
The oxidant stress hypothesis in Parkinson's disease: Evidence supporting it
Authors: Fahn Stanley , Cohen Gerald
Published: January 2005

Oxidant stress, due to the formation of hydrogen peroxide and oxygen‐derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6‐hydroxydopamine and 1‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase. (6) The recent findings of decreased activity of NADH‐CoQ reductase, a mitochondrial complex I enzyme, in substantia nigra and platelets in patients with Parkinson's disease can also be interpreted to be a cause or product of oxidant stress. The identical enzyme abnormality occurs with MPTP toxicity, and this has been associated with increased superoxide anion radical formation. Moreover, mice with increased activity of superoxide dismutase are protected against MPTP toxicity. The evidence favoring the oxidant stress hypothesis is persuasive, but not yet fully established. We believe that this is the best hypothesis available at present.
Lack of JC viral genomic sequences in multiple sclerosis brain tissue by polymerase chain reaction
Authors: Buckle Guy J. , Godec Mark S. , Rubi Jorge U. , Tornatore Carlo , Major Eugene O. , Gibbs Clarence J. , Gajdusek D. Carleton , Asher David M.
Published: January 2005

With DNA extracted from brain specimens from 19 multiple sclerosis, 5 progressive multifocal leukoencephalopathy, 1 Alzheimer's disease, and 8 nonneurological control subjects, polymerase chain reaction was performed using nested sets of primer pairs amplifying segments of the large T and VP1 antigen‐encoding sequences of JC virus. Both sequences were detected in each of the 5 brain specimens of progressive multifocal leukoencephalopathy but in none of the 19 multiple sclerosis, 1 Alzheimer's disease, or the 8 control brain specimens.
Correlation of myelin basic protein‐like material in cerebrospinal fluid of multiple sclerosis patients with their response to glucocorticoid treatment
Authors: Whitaker John N. , Layton Beverly A. , Herman Paula K. , Kachelhofer R. David , Burgard Sheila , Bartolucci Alfred A.
Published: January 2005

Predictors and laboratory correlates of the response of patients with multiple sclerosis to glucocorticoids are not well defined. Our study was undertaken to determine if the levels of myelin basic protein (MBP)‐like material in cerebrospinal fluid (CSF) might indicate which patients with multiple sclerosis would show a short‐term (5 day) or intermediateterm (40 day) improvement of at least a full‐grade Kurtzke disability score after initiating treatment with glucocorticoids. A total of 62 patients received 71 courses of treatment consisting of 5 days of intravenous methylprednisolone (500 mg per day) usually followed by a 4‐week tapering dose of oral prednisone. CSF was obtained before initiation of treatment and analyzed for MBP‐like material by radioimmunoassay. Results were analyzed by χ2 tests of association and by logistic regression. Individuals having a CSF MBP‐like material level of ≥0.1 ng/ml overall showed a greater likelihood of continued improvement at day 40 (p = 0.014) or further improvement between days 5 and 40 (p = 0.003). Those in the first 15 days of worsening and with an elevated CSF MBP‐like level were more likely to respond by day 5. Relapsing–remitting and relapsing–progressive forms of the disease were more likely to respond at both time points than were patients with primary or secondary chronic progressive patterns. The Kurtzke disability score at entry and the major anatomical site of the central nervous system symptomatically affected were not predictive of outcome at either time. These studies indicate that the level of CSF MBP‐like material may help select those patients with multiple sclerosis who will show a response to short‐term glucocorticoid or other treatment.
Thyrotropin‐Releasing hormone gene expression and receptors are differentially modified in limbic foci by seizures
Authors: Kubek M. J. , Knoblach S. M. , Sharif N. A. , Burt D. R. , Buterbaugh G. G. , Fuson K. S.
Published: January 2005

Previous studies using two seizure paradigms, electronconvulsive shock and kindling, suggested potential sites of endogenous thyrotropin‐releasing hormone (TRH) action in specific epileptogenic areas. We studied TRH gene expression and TRH receptors in rat limbic areas using the kindling model of epilepsy. Immunoassayable TRH increased 4‐ to 20‐fold over control levels in specific subregions of the hippocampus 24 hours after a single stage 5 seizure. Concurrently, TRH receptor binding was significantly reduced in hippocampal (23–39%) and amygdaloid (21–22%) membranes. Dramatic temporal and spatial changes in prepro‐TRH messenger RNA were visualized by in situ hybridization histochemistry in the hippocampal dentate gyrus, the piriform cortex, and the amygdala. Peak hybridization occured 6 and 12 hours postictally in these loci and returned toward basal levels by 24 hours. These results are consistent with the hypothesis that TRH may have an important role in the pathophysiology of epilepsy by modulating excitatory processes.
Temporal neocortical role in ictal experiential phenomena
Authors: Blume Warren T. , Girvin John P. , Stenerson Paul
Published: January 2005

Resection of a left temporal neocortical tumor, preserving the amygdala and hippocampus, permanently abolished ictal illusions in a 20‐year‐old‐man, suggesting that neocortical epileptic discharge is essential in the production of the experiential phenomena of seizures. In light of other works demonstrating amygdala and hippocampal participation, we propose that ictal experiential phenomena represent simultaneous epileptic discharge of the temporal neocortex and the limbic system.
Spastic ataxia associated with human T‐cell lymphotrophic virus type II infection
Authors: Harrington William J. , Sheremata William , Hjelle Brain , Dube Dipak K. , Bradshaw Peggy , Foung Steven K. H. , Snodgrass Susan , Toedter Gary , Cabral Lisa , Poiesz Bernard
Published: January 2005

Human T‐cell lymphotropic virus type one (HTLV‐1) is associated with tropical spastic paraparesis or HTLV‐I‐associated myelopathy. We report 2 women with a spastic ataxic illness similar to HTLV‐I‐associated myelopathy infected solely with HTLV‐II. Identification of HTLV‐II infection was made serologically, by polymerase chain reaction, and by viral culture (in 1 woman). One woman, treated with 200 mg of danazol orally, three times daily, had pronounced improvement in ambulation, nocturnal spasticity, and nighttime urinary frequency. It appears that infection with HTLV‐II may cause an illness similar to HTLV‐I‐associated myelopathy, but distinguished by the presence of ataxia.
Dementia in Parkinson's disease: Biochemical evidence for cortical involvement using the immunodetection of abnormal tau proteins
Authors: Vermersch Patrick , Delacourte André , Javoy‐Agid France , Hauw Jean‐Jacques , Agid Yves
Published: January 2005

In order to elucidate the neurochemical basis of the dementia of Parkinson's disease, we compared samples of cerebral cortex from 24 nondemented parkinsonian patients and parkinsonian patients with various degrees of dementia, with those from patients with Alzheimer's disease and control subjects, using a quantitative Western blot analysis. An anti‐paired helical filaments antibody was used for the immunodetection of the abnormally phosphorylated Tau proteins 55,64, and 69, which are known to be specific and reliable biochemical markers of Alzaheimer‐type neurofibrillary degeneration. The frequency and intensity of immunodetection of the abnormal Tau triplet were higher in the demented parkinsonian subgroups than in the nondemented parkinsonian subgroup in the prefrontal area, temporal cortex, and entorhinal cortex but not in either the occipital or the cingular cortex. A quantification of abnormal Tau triplet by densaitometry showed that unlike the results obtained in Alzheimer patients, the intensity of lesions in the cerebral cortex of the most demented parkinsonian patients was more severe in the prefrontal area versus the temporal area. This study (1) gives biochemical evidence for Alzheimer‐type changes in the cortex of demented parkinsonian patients and (2) suggests that lesions of the prefrontal cortex may significantly contribute to the occurrence of cognitive changes at least in some patients with Parkinson's disease.
Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor
Authors: Britton T. C. , Thompson P. D. , Day B. L. , Rothwell J. C. , Findley L. J. , Marsden C. D.
Published: January 2005

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time‐locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.
Amygdaloid sclerosis in temporal lobe epilepsy
Authors: Hudson Lawrence P. , Munoz David G. , Miller Laurie , McLachlan Richard S. , Girvin John P. , Blume Warren T.
Published: January 2005

Hippocampal sclerosis is the sole abnormality found in approximately 65% of all temporal lobe specimens resected for intractable temporal lobe epilepsy. Up to 27% of en bloc temporal lobectomy specimens, howevery, show no definitive pathological changes. The lateral amygdaloid nucleus from 8 consecutive patients who underwent temporal lobectomy in whom no definitive hippocampal pathology was present and corresponding tissue from 8 consecutive patients with hippocampal sclerosis were subjected to quantitative estimation of neuronal density and astrogliosis. As compared to amygdaloid tissue from autopsy control subjects with no history of neurological disease, both the patient group with and that without hippocampal sclerosis consistently exhibited severe neuronal loss and gliosis with no quantitative differences between the two groups. Bliaded clinical review of both groups of patients revealed that the development of hippocampal sclerosis was associated with a history of early brain insult; this history was absent in patients with isolated amygdaloid sclerosis, Neuropsychological resting prior to surgery demonstrated that patients with hippocampal sclerosis displayed a greater degree of momory impairment than did those without hippocampal sclerosis. We conclude that amygdaloid sclerosis occurs in the absence of hippocampal sclerosis, and that these patients from a distinct group with no history of early brain insult and milder memory impairment than that seen in patients afficted with hippocampal sclerosis.
The effects of X monosomy on brain development: Monozygotic twins discorcant for Turner's syndrome
Authors: Reiss Allan L. , Freund Lisa , Plotnick Leslie , Baumgardner Thomas , Green Kathleen , Sozer Amanda C. , Reader Mark , Boehm Corinne , Denckla Martha B.
Published: January 2005

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3‐point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal–occipital, and left parietal‐perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in the twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.