bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetrical ocular pursuit with posterior fossa tumors
Authors: Furman Joseph M. R. , Hurtt Mark R. , Hirsch William L.
Published: January 2005

We report two patients with posterior fossa neoplasms who demonstrated asymmetrically impaired horizontal ocular pursuit documented with electrooculography. One patient had impaired pursuit contralateral to a pontomedullary lesion, whereas the second patient had impaired pursuit ipsilateral to a pontocerebellar lesion. These patients demonstrate that posterior fossa lesions may impair ocular pursuit either contralaterally or ipsilaterally unlike cerebral hemispheric lesions, which impair ocular pursuit ipsilaterally or bilaterally.
Recurrent attacks of amaurosis fugax treated with calcium channel blocker
Authors: Winterkorn Jacqueline M. S. , Teman Allen Jay
Published: January 2005

Vasospasm may be one of the causes of amaurosis fugax. A patient is reported who daily experienced multiple brief episodes of amaurosis fugax. The absence of physical, laboratory, or radiographic evidence for thromboembolism, hemodynamic compromise, or vasculitis, suggested that the amaurosis might be caused by vasospasm. This hypothesis was supported by cessation of the attacks of amaurosis when the patient was treated with a calcium channel blocker.
The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma
Authors: Salzman Steven K. , Puniak Michael A. , Liu Zhong‐jun , Maitland‐Heriot Richard P. , Freeman Gina M. , Agresta Cynthia A.
Published: January 2005

The ability of the serotonin antagonist mianserin to improve neurological recovery after graded impact trauma to the thoracic region of the spinal cord was compared to that of cyproheptadine and ketanserin in pentobarbital‐anesthetized rats. Spinal cord injury was produced at T‐10 by the weight‐drop method and confirmed by the disappearance of the somatosensory‐evoked response during the subsequent 15 minutes. In all experiments, drug or vehicle treatments were randomly administered as a single intravenous bolus 15 minutes after injury. Functional outcome was blindly assessed for 2 weeks after injury using a modified Tarlov scale, and in some cases, the Rivlin‐Tator angleboard test. The survival of descending raphe‐spinal axons was determined by the measurement of serotonin in postmortem spinal tissues located above and below the site of injury. In separate acute experiments, the physiological and hemodynamic correlates of a 50 gm cm injury and either mianserin or vehicle injection were examined, as were the effects on serotonin content and metabolism in spinal tissues harvested 30 minutes after injury. All doses of mainserin were associated with some index of improved recovery following a 50 gm cm injury, with a 1‐mg/kg dose being clearly superior. Both ketanserin (0.1 mg/kg) and cyproheptadine (2 mg/kg) displayed marginal therapeutic actions for 50 gm cm injuries. In acute studies, mianserin at 1 mg/kg was associated with the preservation of posttraumatic spinal cord blood flow at T‐12 as well as a pronounced alteration in postmortem spinal serotonin content and metabolism, in contrast to vehicle control treatments. These data lend further support to a serotonergic hypothesis of secondary spinal cord injury and suggest the potential use of mianserin for the acute treatment of spinal cord injury.
Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment
Authors: Terry Robert D. , Masliah Eliezer , Salmon David P. , Butters Nelson , DeTeresa Richard , Hill Robert , Hansen Lawrence A. , Katzman Robert
Published: January 2005

We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.
Somatostatin replacement therapy for alzheimer dementia
Authors: Mouradian M. Maral , Blin Jerome , Giuffra Marianne , Heuser Isabella J. E. , Baronti Fabio , Ownby John , Chase Thomas N.
Published: January 2005

Somatostatin is consistently diminished in brains of patients with Alzheimer's disease. To evaluate whether pharmacological restoration of this transmitter deficit has therapeutic value, the synthetic analogue octreotide was administered intravenously to 14 Alzheimer patients under double‐blind, placebo‐controlled conditions. At the highest dose administered, spinal fluid concentrations approximated those found in brains of experimental animals receiving behaviorally effective amounts of the drug. Neuropsychological testing, however, showed no clinically significant improvement. Coadministration of octreotide and physostigmine to 1 patient also failed to improve cognition. Positron emission tomographic studies in 6 patients revealed a generalized decrease in glucose metabolism as a result of octreotide infusion. These findings suggest that stimulation of the somatostatin system has no value in the symptomatic treatment of Alzheimer dementia.
The use of hospital discharge data for public health surveillance of guillain‐barré syndrome
Authors: Koobatian Thomas J. , Birkhead Guthrie S. , Schramm Margaret M. , Vogt Richard L.
Published: January 2005

The sensitivity of passive reporting of Guillain‐Barré syndrome (GBS) to the Vermont Department of Health from 1980 to 1985 was compared to that of computerized hospital discharge abstract data. Written hospital discharge summaries were reviewed for clinical data to validate the computerized abstracts. In all, 51 definite and probable cases of GBS were identified from hospital data during a period when only 4 cases (8%) had been reported to the health department through passive physician reporting. Based on the hospital data, the incidence of this syndrome in Vermont was 1.6/100,000 population/year. The incidence rate for males was 1.5 times that for females. No geographical or seasonal clustering of cases was found. These epidemiological features are consistent with previously published data on the syndrome and suggest that the incidence has not changed significantly in the past 10 years. Incidence rates for GBS based on passively reported cases markedly underestimate the true incidence rate. Although limited by the lack of timeliness for public health surveillance, computerized hospital discharge data are readily available in many states and may be more sensitive in detecting cases, compared to passive surveillance. They may be a useful tool for establishing baseline rates and examining longterm trends for selected acute diseases like GBS for which there are well‐established diagnostic criteria and that usually result in hospitalization.
Neurotensin receptors in human meningiomas
Authors: Przedborski Serge , Levivier Marc , Cadet Jean Lud
Published: January 2005

We have investigated the presence of neurotensin receptors in human meningiomas by in vitro binding autoradiography. Ten of the 12 meningiomas tested displayed specific {3H}neurotensin binding. All meningothelial (n = 3) and transitional (n = 5) meningiomas were positive, whereas only 2 of the 4 fibroblastic meningiomas showed measurable concentrations of neurotensin binding sites. Within the tumors, {3H}neurotensin binding was preferentially observed in syncytial areas. Saturation experiments showed that the maximal binding capacity (Bmax) greatly varied among tumors, ranging from low values to more than 290 fmol/mg of protein. All positive tumors had neurotensin binding sites with a dissociation constant (kd) within the nanomolar range and a pharmacological specificity for {3H}neurotensin similar to neurotensin receptors.
Visual attentional disturbance with unilateral lesions in the basal ganglia and deep white matter
Authors: Sakashita Yasuo
Published: January 2005

To elucidate the role of the basal ganglia and deep white matter in the visual attention mechanism, a new visual attention task was carried out by 15 patients, 9 with left‐side and 6 with right‐side basal ganglia and/or deep white matter damage without visual field defects, and by 12 normal subjects. Their reaction times were recorded in response to a random visual stimulation by pushing a button with the hand ipsilateral to the side of the lesion. All the patients with damage to the right side of the brain had a longer reaction time in the left space than in the right or middle space. With conventional tests, only one of them showed left unilateral spatial neglect. Seven of the 9 patients with a left lesion had a significantly longer reaction time in the right space than in the left. None had unilateral spatial neglect. Both the right and left brain‐damaged groups showed longer reaction times in both spaces, compared to the normal groups. There was no significant difference in reaction time among the control subjects. These findings suggest that the basal ganglia and deep white matter in each hemisphere play some role in directing visual attentional factors into both spaces. Visual attentional disturbance was highly evident even with left‐side brain damage, and this kind of disturbance is not usually revealed with the current tasks used for testing unilateral spatial neglect.
Effects of gangliosides on the expression of autoimmune demyelination in the peripheral nervous system
Authors: Ponzin Diego , Menegus Anna Maria , Kirschner Gunther , Nunzi M. Grazia , Fiori Mario G. , Raine Cedric S.
Published: January 2005

To test whether gangliosides (GA) might exert neuritogenic effects in vivo, experimental allergic neuritis (EAN) was studied clinically, neuropathologically, and immunologically in Lewis rats immunized with bovine peripheral nerve, P2 myelin protein, P2 myelin protein plus two different doses of GA, P2 with galactocerebroside (GC), and GA alone, each emulsified in adjuvant. All except the GA‐treated group developed signs of EAN between days 11 and 14 after the injection. Rats immunized with P2 alone were the most severely affected. Rats given P2 plus GA and those given P2 plus GC displayed a significantly lower clinical score. Histological analysis revealed a comparable degree of inflammation of the peripheral nervous system and demyelination in the spinal nerve roots of bovine peripheral nerve‐and P2‐immunized rats. The P2 plus GA and P2 plus GC groups revealed similar degrees of pathology in the spinal nerve roots but the latter group stood apart from the rest in that it showed widespread peripheral nervous system changes extending distally into the sciatic nerve. Serological analysis demonstrated that P2 and GC, but not GA, elicited antibody (IgG) responses, but there was no correlation between antibody titer and clinical or histological involvement. The present data fail to support an enhancing role for gangliosides in the expression of EAN and, by extrapolation, in the Guillain‐Barré syndrome, for which EAN serves as the laboratory model, and in which suggestions have been made that antibodies to GA may have pathogenetic significance.
Mitochondrial DNA sequence analysis in congenital myotonic dystrophy
Authors: Thyagarajan D. , Byrne E. , Noer S. , Lertrit P. , Utthanophol P. , Kapsa R. , Marzuki S.
Published: January 2005

Mitochondrial genetic modifying factors have been suspected in several autosomally inherited diseases. The congenital variant of myotonic dystrophy, in which there is a striking maternal inheritance pattern, is a likely candidate disease. To investigate this possibility, we sequenced completely the mitochondrial genome in 2 patients with congential myotonic dystrophy. Comparison of the two sequences with control data failed to reveal a specific nucleotide variant or length variant in this disease. We conclude that a mitochondrial genetic modifying factor is not present in congenital myotonic dystrophy.
Excitatory amino acid binding sites in the caudate nucleus and frontal cortex of huntington's disease
Authors: Dure Leon S. , Young Anne B. , Penney John B.
Published: January 2005

Huntington's disease is a dominantly inherited, progressive neurodegenerative disorder causing marked pathology in the basal ganglia. The pathophysiology of the selective neuronal death in as yet unknown, but evidence suggests that the neurotoxicity may result from endogenous substances acting at excitatory amino acid receptors. Previous data have shown a selective decrease in binding to one class of glutamate receptors, the N‐methyl‐D‐aspartate (NMDA) receptor in the putamen of Huntington's disease. The present study was undertaken to determine the relative density of binding to all of the currently defined subpopulations of excitatory amino acid receptors in the caudate nuclei and frontal cortex of patients with Huntington's disease and of control subjects, using quantitative in vitro autoradiography. NMDA, MK‐801, glycine, kainate, and α‐amino‐3‐hydroxy‐5‐methylisoxazole propionic acid (AMPA) receptor binding were all decreased to a similar extent (50–60°). Binding to the metabotropic quisqualate receptor and to the non‐NMDA, nonkainate, nonquisqualate (NNKQ) site was decreased nonsignificantly by 31° and 26°, respectively. Autoradiograms of NMDA, MK‐801, AMPA, kainate, metabotropic, and NNKQ receptors in caudates revealed an inhomogeneous pattern of binding that is different from the binding pattern seen in control caudates. Binding to all receptor subtypes was the same in the frontal cortex from Huntington's disease patients and control subjects. The data suggest that no single excitatory amino acid receptor is selectively decreased in the caudate of Huntington's disease.
Changes of muscarinic cholinergic binding by lymphocytes in parkinson's disease with and without dementia
Authors: Rabey José Martin , Grynberg Elisheva , Graff Eran
Published: January 2005

We compared the muscarinic cholinergic binding in lymphocytes of 44 patients with idiopathic Parkinson's disease with 23 age‐matched normal volunteers, using [3H]quinuclidinyl benzilate. In 24 patients with Parkinson's disease without dementia, binding was normal in 12, below control values in 6, whereas the remaining 6 (all on anticholinergic medication) showed very high binding. In all 20 patients with Parkinson's disease and with dementia, the binding was below control levels, indicating that in these patients, as in patients with Alzheimer's dementia, the cholinergic muscarinic binding by lymphocytes is reduced.
Relapsing and remitting human immunodeficiency virus—associated leukoencephalomyelopathy
Authors: Berger Joseph R. , Tornatore Carlo , Major Eugene O. , Bruce Jocelyn , Shapshak Paul , Yoshioka Masaru , Houff Sydney , Sheremata William , Horton Gerald F. , Landy Howard
Published: January 2005

We describe a 33‐year‐old homosexual man with a steroid‐responsive, remitting and relapsing leukoencephalopathy associated with recent human immunodeficiency virus type 1 (HIV‐1) seroconversion. Biopsy of a parieto‐occipital lesion revealed demyelination and astrogliosis with focal necrosis. Detailed investigations demonstrated no pathogens in the brain other than HIV‐1. This patient illustrates that a neurological disorder clinically indistinguishable from multiple sclerosis may be the presenting manifestation of HIV‐1 infection and may occur in the absence of clinically significant immunosuppression.
Neurofilament and neural cell adhesion molecule immunocytochemistry of Huntington's disease striatum
Authors: Nihei Kuninobu , Kowall Neil W.
Published: January 2005

We examined normal and Huntington's disease (HD) human striatum with specific monoclonal antibodies to nonphosphorylated (SMI 32) and phosphorylated (SMI 31) neurofilament and neural cell adhesion molecule (NCAM). SMI 32 identifies medium‐sized neuronal perikarya and dendrites in normal striatum. Axons are not immunoreactive. In high‐grade HD striatum (grades 3 and 4) SMI 32 neurons are morphologically abnormal and significantly depleted. Dendritic arbors are intensely immunoreactive, tortuous, and fragmented, especially in the subependymal zone. Proliferative SMI 32–positive sprout‐like structures and axon‐like processes are seen. SMI 31 normally stains a fine meshwork of axon‐like processes that become intensely immunoreactive, condensed, convoluted, and fragmented in HD. NCAM staining is minimal in normal striatum, but, in HD striatum, many dot‐ and thread‐like structures are found, especially in the subependymal region. The abnormalities revealed by SMI 31, SMI 32, and NCAM suggest that neurofilament phosphorylation is altered and growth related proteins are reexpressed in HD. Dephosphorylation and destabilization of the cytoskeleton may contribute to neuronal injury and death in HD.
Breathing disorders during sleep in myasthenia gravis
Authors: Quera‐Salva M. A. , Guilleminault C. , Chevret S. , Troche G. , Fromageot C. , McCann C. Crowe , Stoos R. , de Lattre J. , Raphael J. C. , Gajdos Ph.
Published: January 2005

Twenty consecutive patients (16 women and 4 men), with a mean age of 40 years, who were diagnosed and treated for myasthenia gravis were enrolled in a prospective investigation aimed at determining the amount of respiratory disturbance occurring during sleep while they received treatment. Patients were clinically evaluated to determine body mass index, presence of upper airway anatomical abnormalities, level of functional capacity and activity scored from 1 to 5, and presence of sleep‐related complaints. They underwent daytime pulmonary function tests, determination of maximal static inspiratory pressure, measurement of transdiaphragmatic pressure, and measurement of arterial blood gas levels. Polygraphic monitoring during sleep, evaluating respiration and oxygen saturation, was also performed. Results indicated that in the studied population, all subjects had evidence of daytime diaphragmatic weakness as demonstrated by transdiaphragmatic pressure measurements, independent of the degree of autonomy and functional capacity and activity level reached. Older patients with moderately increased body mass index, abnormal total lung capacity, and abnormal daytime blood gas concentrations were the primary candidates for development of diaphragmatic sleep apneas and hypopneas, and oxygen desaturation of less than 90% during sleep. However, these clear indicators were not found in all subjects with sleep‐related disordered breathing. Rapid‐eye‐movement sleep was the time of highest breathing vulnerability during sleep. Sleep‐related complaints may also help identify subjects at risk for abnormal breathing during sleep, even when daytime functional activity is judged normal.
The transcranial doppler appearance of acute carotid artery occlusion
Authors: Giller Cole A. , Mathews Dana , Purdy Phillip , Kopitnik Thomas A. , Batjer H. Hunt , Samson Duke S.
Published: January 2005

Transcranial Doppler ultrasound is a noninvasive technique of cerebral blood velocity measurement that is being increasingly used to detect untoward hemodynamic changes. In this report, we describe striking transcranial Doppler ultrasound changes occurring in 2 patients after cervical carotid artery occlusion that led to cerebral infarction. These changes consist of the sudden appearance of a Doppler signal of extremely low pulsatility and moderately high velocity in the middle cerebral artery distribution. In 1 patient, this signal was the first sign of carotid occlusion. We suggest that these transcranial Doppler ultrasound changes can provide an early warning of carotid artery compromise.
Familial periodic cerebellar ataxia: A problem of cerebellar intracellular pH homeostasis
Authors: Bain P. G. , O'Brien M. D. , Keevil S. F. , Porter D. A.
Published: January 2005

Six affected members of two families with familial periodic cerebellar ataxia were relieved of their symptoms with oral acetazolamide. Phosphorus 31 (31P) nuclear magnetic resonance spectroscopy showed abnormal intracellular pH levels in the cerebellum of all subjects when they were not treated. These levels returned to normal with treatment. Cerebral pH values were also measured in one family and were normal before and after treatment. An additional 3 patients with similar attacks, but without a family history, had normal untreated pH values in the cerebellum and cerebrum.
Infantile spasms: II. Lenticular nuceli and brain stem activation on positron emission tomography
Authors: Chugani Harry T. , Shewmon D. Alan , Sankar Raman , Chen Benjamin C. , Phelps Michael E.
Published: January 2005

Infantile spasms are generalized sezures specific to early infancy, and are believed to result from complex cortical‐subcortical interactions during a critical period of development. We used positorn emission tomography (PET) to determine local cerebral metabolic rates for glucose (lCMRGlc) in 44 infants with spasms, in an attempt to define the neuroanatomical substrates that mediate these seizures. All infants were studied in the awake state during continuous electroencephalographic monitoring. The most consistent abnormality on PET, seen in 32 infants, was the symmetrical increase in lCMRGlc in the lenticular nuclei, compared to age‐matched normal infants (p < 0.05). In 21 infants, even though the brain stem appeared to be visually more prominent compared to normal infants, statistically significant differences could not be demostrated. Relative hypermetabolism of the lenticular nuceli (1) occured irrespective of whether the spasms were cryptogenic or symptomatic, (2) was associated with focal cortical hypometabolism in 22 and focal cortical hypermetabolism in 5 of the 44 infants, and (3) was not characterized by any specific electroencephalographic abnormality during PET. These findings suggest that the lenticular nuclei may contribute to the pathophysiological state that predisposes to infantile spasms, and is consistent with the observation that spasms are clinically symmetrical even when focal cortical lesions are present. A scheme describing the neuronal circuitry likely to be involved in the generation of infantile spasms is proposed.
The chiari type I malformation in two monozygotic twins and first‐degree relatives
Authors: Stovner Lars Jacob , Cappelen Johan , Nilsen Gunnar , Sjaastad Ottar
Published: January 2005

The presence of the Chiari type I malformation in 2 adult monozygotic female twins, their mother, and possibly in 2 of their 4 daughters is reported. The diagnosis was made by magnetic resonance imaging and confirmed at the time of surgery in 1 twin. Monozygosity of the twins was proved by DNA typing. The disorder in the present family should probably be classified together with the autosomal dominant craniocervical malformations. Nongenetic factors also seem to be important because the twins were discordant for the extent of herniation of the cerebellar tonsils and the presence of syringmyelia.
The spectrum of neurological disease in patients with systemic cancer
Authors: Clouston Paul D. , DeAngelis Lisa M. , Posner Jerome B.
Published: January 2005

To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological sysmptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan–Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 851 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatisc disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty‐three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer‐related and nonmetastatisc neurological problems.
“Resetting” of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and 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 response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors.
Hypervolemic therapy prevents volume contraction but not hyponatremia following subarachnoid hemorrhage
Authors: Diringer Michael N. , Wu Katherine C. , Verbalis Joseph G. , Hanley Daniel F.
Published: January 2005

Hyponatremia is common following subarachnoid hemorrhage and has alternatively been attributed to either the inappropriate secretion of antidiuretic hormone or natriuresis causing intravascular volume contraction. We prospectively studied body sodium and intravascular volume regulation in 19 patients, beginning within 3 days after acute aneurysmal subarachnoid hemorrhage occurred, in order to determine the impact of hypervolemic therapy on both hyponatremia and volume contraction and to ascertain whether humoral factors account for hyponatremia. Serial measurements of plasma arginine vasopressin, atrial natriuretic factor, renin activity, aldosterone, and catecholamines were correlated with body sodium and fluid balance, change in blood volume, serum sodium concentration, and osmolality. Six patients (32%) developed hyponatremia, but only 2 had a negative sodium balance. In most patients, levels of atrial natriuretic factor were elevated, while plasma renin activity and aldosterone concentrations were generally suppressed. Plasma arginine vasopressin levels were not suppressed during hypo‐osmolality and did not correlate with serum osmolality in hyponatremic patients. Only 1 patient had a decrease in blood volume, which was associated with marked rises in aldosterone and plasma renin activity, but normal serum sodium and plasma atrial natriuretic factor levels. We conclude that following subarachnoid hemorrhage: (1) Hypervolemic therapy prevents volume contraction but not hyponatremia, (2) humoral factors may favor both sodium loss and water retention, and (3) arginine vasopressin regulation is disturbed and may contribute to hyponatremia.
Selective D2 receptor stimulation induces dyskinesia in parkinsonian monkeys
Authors: Luquin M. Rosario , Laguna Janeth , Obeso Jose A.
Published: January 2005

Stimulation of D1 striatal receptors has been proposed as the main mechanism mediating levodopa‐induced dyskinesia in Parkinson's disease. We used (+)‐PHNO, a selective D2 agonist, as the only treatment in 6 cynomolgus monkeys made parkinsonian by repeated 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine administration. All animals developed choreic dyskinesia after a mean treatment period of 12.8 days (range, 1–29). Administration of the D1 antagonist SCH‐23390 1 hour before administration of (+)‐PHNO did not change the dyskinesia. These results indicate that drug‐induced dyskinesia in a primate model of Parkinson's disease is not solely induced by D1 receptor activation.
Ascorbat neurotoxicity in cortical cell culture
Authors: Hisanaga Kinya , Sagar Stephen M. , Sharp Frank R.
Published: January 2005

Ascorbate (vitamin C)is believed to act as a neuromodulator that facilitates the release of neurotransmitters and inhibits neurotransmitter binding to receptors, including dopamine and N‐methyl‐D‐aspartate receptors. Extracellular levels of ascorbate are known to reach the low millimolar range after ischemic brain injury. This study shows that treatment of cultured cortical neurons with micromolar to low millimolar ascorbate first inhibits total protein synthesis and then results in late neuronal death. Astrocytes are much less vulnerable to ascorbate than neurons. Ascorbate may exacerbate neuronal and glial damage after brain ischemia, and it may play a pathological role in other neurological diseases.
Cholinesterases in the amyloid angiopathy of Alzheimer's disease
Authors: Mesulam Marsel , Carson Keith , Price Bruce , Geula Changiz
Published: January 2005

Vessels affected by amyloid angiopathy in patients with Alzheimer's disease also displayed intense acetylcholinestearase and butyrylcholinesterase activity when examined by light and electron microscopy. The enzymatic properties of the vessel‐bound cholinesterases were identical to those of the cholinesterases associated with senile plaques and neurofibrillary tangles. This cholinesterase activity is of unknown origin but represents one of the very few features common to all the major pathological markers of Alzheimer's disease.
Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot‐Marie‐Tooth disease type 1)
Authors: Hallam P. J. , Harding A. E. , Berciano J. , Barker D. F. , Malcolm S.
Published: January 2005

Hereditary motor and sensory neuropathy type I (HMSNI), also known as Charcot‐Marie‐Tooth disease type 1 (CMT1), has been shown to be genetically heterogeneous. A major gene maps to chromosome 17 (CMT1A). A set of loci, D17S122, D17S125, and D17S124, show tight linkage to the CMT1A locus, and a duplication of D17S122 has been detected in some families. We show that the locus D17S122 is duplicated in affected individuals from 7 informative families with HMSNI. The duplication was demonstrated either by differences in hybridization densities between two bands of a restriction fragment length polymorphism or by the presence of all three alleles. No normal individual had the duplication. A single recombinant exists between the MspI polymorphism of D17S122 and the duplicated band, suggesting that the duplication is of considerable size. Patients with HMSN type II do not show the duplication. These findings will have considerable impact on the diagnosis of chronic demyelinating neuropathies, in patients with or without similarly affected relatives.
Monoaminergic and cholinergic synaptic markers in the nucleus basalis of meynert (nbM): Normal age‐related changes and the effect of heart disease and Alzheimer's disease
Authors: Sparks D. Larry , Hunsaker John C. , Slevin John T. , DeKosky Steven T. , Kryscio Richard J. , Markesbery William R.
Published: January 2005

Neurotransmitter markers for acetylcholine, serotonin (5‐HT), and dopamine (DA) were measured in autopsied human nucleus basalis of Meynert (nbM) from nondemented individuals without heart disease (non‐HD) (age range, 4–84 years; n = 77), nondemented individuals with heart disease (HD) (age range, 57–92 years; n = 23), and individuals with Alzheimer's disease (AD) (age range, 59–92 years; n = 22). No significant differences in any chemical marker were found between age‐matched HD and non‐HD individuals. The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and {3H}spiperone binding were regionally distributed within the nbM in control (non‐HD) subjects less than 54 years of age. The activity of AChE, 5‐{3H}HT binding, and the content of homovanillic acid (HVA), 5‐hydroxyindoleacetic acid (5‐HIAA), and 5‐HT were regionally distributed in the nbM in non‐HD, HD, and AD subjects more than 54 years of age. The binding of {3H}spiperone was regionally distributed in the nbM in HD and AD subjects more than 54 years of age, only. Activity of ChAT and AChE, content of 5‐HT, 5‐HIAA, and DA, binding of 5‐{3H}HT, and the turnover number for DA (ratio of HVA/DA) all decreased with increasing age in the non‐HD control population. The content of HVA, binding of {3H}spiperone, and the turnover number for 5‐HT (ratio of 5‐HIAA/5‐HT) did not change with increasing age. Significant reductions in ChAT and AChE activities were found in AD nbM compared with postmortem interval‐ and age‐matched HD and non‐HD individuals. The reduction of 5‐HT and 5‐HIAA content and {3H}spiperone binding in individuals with AD of all ages suggests a loss of functional serotonergic innervation of the nbM. Dopaminergic synaptic markers were less affected in AD nbM, although turnover numbers for both DA and 5‐HT were increased in AD. Receptor upregulation in response to presynaptic deficits did not occur for DA or 5‐HT.
Startle disease, or hyperekplexia: Response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis
Authors: Ryan Stephen G. , Sherman Stephanie L. , Terry Joseph C. , Sparkes Robert S. , Torres M. Cristina , Mackey Ray W.
Published: January 2005

Familial startle disease (also known as hyperekplexia and congenital “stiff‐man” syndrome) is an autosomal dominant disorder characterized by an exaggerated startle reaction to sudden, unexpected auditory or tactile stimuli; affected neonates also have severe and occasionally fatal hypertonia. We recently encountered a large, five‐generation family with startle disease, and treated 16 patients (including 1 neonate) with clonazepam; all experienced dramatic and sustained improvement. We performed systematic linkage analysis in this family, and found tight linkage between the disease locus and a polymorphic genetic marker locus (colony‐stimulating factor receptor, or CSFIR) that has been physically mapped to chromosome 5q33‐q35. The maximum odds ratio favoring linkage over nonlinkage is greater than 10,000,000:1 (lod score, 7.10) at 3% recombination. Several genes encoding neurotransmitter receptor components have been physically mapped to the subtelomeric region of chromosome 5q, and are thus candidates for the startle disease gene. The availability of additional large pedigrees with startle disease shold facilitate identification and characterization of the gene for this disorder.
Neonatal idiopathic cerebral venous thrombosis: An unrecognized cause of transient seizures or lethargy
Authors: Rivkin Michael J. , Anderson Mary L. , Kaye Edward M.
Published: January 2005

Seven neonates who presented with either lethargy (four infants) or seizures (three infants) were found by magnetic resonance (MR) phase imaging to have idiopathic cerebral venous thrombosis (CVT). Examination showed only hypotonia or hyperreflexia. The presence of CVT was suggested by unenhanced cranial computed tomographic (CT) scans. Conventional MR T1‐ and T2‐weighted images often indicated more extensive thromboses than were suggested by cranial CT. In all infants, MR phase imaging confirmed thromboses by establishing absence of blood flow in cerebral veins or sinuses. No infant received anticoagulation. Lethargy slowly resolved and seizures did not recur. Normal development has been observed thus far in brief follow‐up. The occurrence of seven infants with idiopathic neonatal CVT within a 3‐month period indicates that CVT may be a cause of neonatal seizures or lethargy of unclear cause. MR phase imaging provides a powerful, noninvasive means of confirming the diagnosis. Treatment with anticoagulants does not appear necessary.
The effect of 4‐aminopyridine on clinical signs in multiple sclerosis: A randomized, placebo‐controlled, double‐blind, cross‐over study
Authors: van Diemen Harriët A. M. , Polman Chris H. , van Dongen Theo M. M. M. , van Loenen Arie C. , Nauta Jos J. P. , Taphoorn Martin J. B. , van Walbeek Harm K. , Koetsier Johan C.
Published: January 2005

To find out whether treatment with 4‐aminopyridine is beneficial in multiple sclerosis (MS), 70 patients with definite MS entered into a randomized, double‐blind, placebo‐controlled, cross‐over trial in which they were treated with 4‐aminopyridine and placebo for 12 weeks each (maximum dose, 0.5 mg/kg of body weight). The estimated effect of the treatment as measured with the Kurtzke expanded disability status scale, which was the main evaluation parameter, was 0.28 point (p = 0.001). A significant decrease in the scale score (1.0 point or more) was encountered in 10 patients (16.4%) during oral treatment with 4‐aminopyridine whereas it was not seen during placebo treatment (p < 0.05). A significant subjective improvement (defined as an improvement that significantly affected the activities of normal daily life) was indicated by 18 patients (29.5%) during 4‐aminopyridine treatment and by 1 patient (1.6%) during placebo treatment (p < 0.05). Significant improvements related to 4‐aminopyridine occurred in a number of neurophysiological parameters. No serious side effects were encountered. However, subjective side effects such as paresthesias, dizziness, and light‐headedness were frequently reported during 4‐aminopyridine treatment. Analysis of subgroups revealed that there was no difference in efficacy between those patients randomized to receive 4‐aminopyridine and then placebo and those randomized to receive placebo and then 4‐aminopyridine or between patients with and those without subjective side effects. Especially patients with temperature‐sensitive symptoms and patients characterized by having a longer duration of the disease and being in a progressive phase of the disease were likely to show clear clinical benefit.
Paramedian thalamopeduncular infarction: Clinical syndromes and magnetic resonance imaging
Authors: Tatemichi T. K. , Steinke W. , Duncan C. , Bello J. A. , Odel J. G. , Behrens M. M. , Hilal S. K. , Mohr J. P.
Published: January 2005

We prospectively examined 11 patients with magnetic resonance imaging–documented infarction in the paramedian thalamopeduncular region, which is supplied by the superior mesencephalic and posterior thalamosubthalamic arteries. Variations in the size and rostral–caudal extent of infarction correlated with the following three clinical patterns: (1) With unilateral paramedian mesencephalic infarction, an ipsilateral third nerve paresis was accompanied by mild contralateral hemiparesis or hemiataxia. Contralateral ptosis and impaired upgaze were observed in two patients; one of them showed additional damage to the posterior commissure. (2) With bilateral infarction in the thalamopeduncular junction, involving the mesencephalic reticular formation, supranuclear vertical gaze defects were accompanied by impaired consciousness or memory, and mild aphasia in some patients. Persistent amnesia was observed only when the dominant anterior nucleus or mamillothalamic tract was damaged. (3) With larger thalamopeduncular infarcts, partial or complete third nerve paresis was combined with supranuclear gaze disturbance and delayed contralateral tremor. An unusual gaze disorder, a variant of the vertical “one‐and‐a‐half syndrome,” occurred with a small strategically placed lesion at the thalamopeduncular junction, best explained by selective damage to supranuclear pathways or partial nuclear involvement. The primary cause of these infarctions was embolism to the basilar apex or local atheroma at the origin of the posterior cerebral artery.
Serological α1‐Antichymotrypsin in Down's syndrome and Alzheimer's disease
Authors: Brugge Karen , Katzman Robert , Hill L. Robert , Hansen Lawrence A. , Saitoh Tsunao
Published: January 2005

α1‐Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly elevated in the serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Patients with Down's syndrome are known to develop neuropathological changes of AD by age 40 years and many become demented. Therefore, in the present study, we obtained serum ACT levels from patients with Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control subjects. Newman–Keuls' multiple range test revealed a significantly greater (p < 0.01) mean ACT level in the Autopsy AD (906.4 ± 94.64 mg/L) and Clinical AD (745.00 ± 59.95 mg/L) groups in contrast to the Old Control group (531.00 ± 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33 ± 14.73 mg/L) was not significantly different from that of the Young Control subjects. Furthermore, we did not observe a positive correlation of ACT levels with age in the Down's Syndrome group, in spite of the age‐dependent premature increase in neuropathological changes of AD that are known to occur in patients with Down's syndrome. A positive correlation between serum ACT levels and the density of plaques or tangles, neuropathological hallmarks of AD, in brains of patients with AD also did not exist. Thus, our results suggest that ACT levels may not parallel the development of the classical neuropathological hallmarks of AD.
Interferon‐γ potentiates antibody‐mediated demyelination in vivo
Authors: Vass Karl , Heininger Kurt , Schäfer Bärbel , Linington Christopher , Lassmann Hans
Published: January 2005

The pathogenetic events leading to demyelination in experimental allergic encephalomyelitis and in human multiple sclerosis are still unclear. The involvement of antimyelin antibodies and activated macrophages as effector cells has been postulated. We investigated the synergistic action of the monoclonal antibody 8‐18C5 against myelin/oligodendrocyte glycoprotein and recombinant interferon‐γ on demyelination after simultaneous injection into the subarachnoid space of Sprague‐Dawley rats. After combined injection of anti–myelin/oligodendrocyte glycoprotein antibody and interferon‐γ, electrophysiological and morphological evidence for demyelination was found. Cervical somatosensory evoked potentials and cervical short‐latency somatosensory evoked potentials were significantly delayed, and the demyelinated area in the spinal cord was significantly enlarged when compared to control rats injected with either compound alone. Injection of either an irrelevant antibody and interferon‐γ or of peritoneal macrophages without anti‐myelin/oligodendrocyte glycoprotein antibody and interferon‐γ did not induce demyelination. Our data suggest that the deleterious effect of interferon‐γ on multiple sclerosis may be not only due to its effect on antigen presentation but also due to potentiation of demyelination.
Rapidly progressive autosomal dominant parkinsonism and dementia with pallido‐ponto‐nigral degeneration
Authors: Wszolek Z. K. , Pfeiffer R. F. , Bhatt M. H. , Schelper R. L. , Cordes M. , Snow B. J. , Rodnitzky R. L. , Wolters E. Ch , Arwert F. , Calne D. B.
Published: January 2005

We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6‐fluoro‐L‐dopa(6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD(p < 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkisonism and dementia with pallido‐ponto‐nigral degeneration.
Bacterial toxin superantigens activate human T lymphocytes reactive with myelin autoantigens
Authors: Burns James , Littlefield Kim , Gill Januaryice , Trotter John L.
Published: January 2005

Some bacteria that are common human pathogens produce protein toxins that are potent activators of human T lymphocytes expressing certain types of T‐cell receptors. In this study we examined the ability of staphylococcal toxins to stimulate human T lymphocytes that also recognized the myelin autoantigens myelin basic protein and proteolipid protein. T‐cell populations responding to myelin basic protein or proteolipid protein were isolated from 4 subjects including 1 individual with multiple sclerosis. All myelin antigen‐specific T cells responded in proliferation studies to at least one of the nine superantigenic toxins used in this study. The superantigenic toxins were up to 7 × 105‐fold more potent in proliferation assays than the myelin antigens to which the T cells were initially sensitized. In addition, cytotoxic, myelin basic protein‐reactive T lymphocytes lysed antigen‐presenting cells incubated with superantigenic toxins. These findings demonstrate a mechanism by which some bacterial infections might produce activation of myelin basic protein‐ and proteolipid protein‐reactive T lymphocytes and perhaps contribute to demyelinating disease in humans.