bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese encephalitis: Idenufication of inflammatory cells in cerebrospinal fluid
Authors: Johnson Richard T. , Intralawan Pensri , Puapanwatton Siriraj
Published: January 2005

Fifteen patients with acute encephalitis were studied during the epidemic season of Japanese encephalitis (JE) in Northern Thailand; 13 of 15 proved to have the encephalitis. In serial cerebrospinal fluids and blood samples, mononuclear cells were identified using monoclonal antibodies. In cerebrospinal fluid from the patients with Japanese encephalitis, T cells predominated with a 4.2:1 ratio of T helper/inducer cells to T suppressor/cytotoxic cells; B cells and macrophages were often present but in small numbers compared to their presence in blood. Distribution of cell types did not vary between the first and fifth day of hospitalization, were similar in fatal and nonfatal cases, and were unaffected by administration of steroids.
Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane–bound zinc in erythrocytes from patients with multiple sclerosis
Authors: Ho Shih‐Yieh , Catalanotto Frank A. , Lisak Robert P. , Dore‐Duffy Paula
Published: January 2005

Previous studies have shown that zinc levels in erythrocytes are significantly elevated in patients with multiple sclerosis (MS). To examine the correlation between erythrocyte Zn levels and disease activity, we measured erythrocyte Zn levels longitudinally. Levels were dramatically decreased during a clinically documented exacerbation of MS. To determine the localization of increased Zn levels in MS erythrocytes, we employed standard techniques for the isolation of nonhemoglobin erythrocyte membrane ghosts. Patients with MS had three times more Zn in ghost material than did controls. Chloroform–methanol extraction in erythrocyte ghosts followed by determination of Zn levels indicated that most of the membrane‐bound Zn was associated with the lipid‐soluble fraction. Non‐lipid‐associated Zn and total membrane protein concentration were similar in MS and control samples. Results suggest that mechanisms which govern cellular availability, compartmentalization of Zn, or the binding of Zn to cell surface membranes may be altered in patients with MS, and that these mechanisms vary with disease activity.
Changes in epileptic spike configuration associated with attainment of seizure control
Authors: Frost James D. , Kellaway Peter , Hrachovy Richard A. , Glaze Daniel G. , Mizrahi Eli M.
Published: January 2005

This study provides preliminary evidence that computer‐derived parameters of interictal spike waveforms can be used to assess seizures hazard in a quantitative manner. Thirteen children with spike foci and simple or complex partial seizures were studied before and during treatment with carbamazepine or phenobarbital; spike parameters were determined from 5‐ to 30‐minute electroencephalographic samples obtained during non–rapid eye movement sleep. Measurements included spike amplitude, duration, and sharpness, and a mathematical combination of these three parameters (the composite spike parameter). Achievement of seizure control was associated with a decrease in spike amplitude, duration, and composite spike parameter, and an increase in normalized sharpness, compared to baseline values. These result suggest that this method may provide a prospective means for estimating drug efficacy that can be applied shortly after attainment of steady‐state serum drug levels.
Inflammatory demyelinating peripheral neuropathies associated with human T‐cell lymphotropic virus type III infection
Authors: Cornblath David R. , McArthur Justin C. , Kennedy Peter G. E. , Witte Arnold S. , Griffin John W.
Published: January 2005

Nine patients with inflammatory demyelinating polyneuropathies (IDP) were found to have human T‐cell lymphotropic virus type III (HTLV‐III) infection. The 8 men, 6 of whom were homosexual, and 1 woman, a former intravenous drug user, presented with progressive weakness. Two had lymphadenopathy but all were otherwise asymptomatic. Six had chronic IDP and 3 had Guillain‐Barré syndrome. In addition to an elevated cerebrospinal fluid (CSF) protein level (mean, 193 mg/dl), most patients had cerebrospinal fluid pleocytosis (mean, 23 cells/mm3), a distinctive feature. All had reduced T4:T8 T‐cell ratios. Results of nerve conduction studies were characteristic of demyelination. Nerve biopsies revealed intense inflammatory cell infiltrates and macrophage‐mediated demyelination. The patients recovered either spontaneously or following treatment with corticosteroids or plasmapheresis. During a mean interval of 20 months after presentation, only 1 patient had developed acquired immune deficiency syndrome. Patients with HTLV‐III infection have disordered immune function, and the mechanism of the development of the IDP is likely to be immunopathogenic. As a result of our experience, we suggest that all patients with IDP be tested for evidence of HTLV‐III infection. We also found, although in uncontrolled trials, that treatment with either prednisone or plasmapheresis was followed by clinical improvement; since plasmapheresis is not likely to further depress cell‐mediated immunity, we suggest that it be the initial therapy.
Latencies of visually guided saccades in unilateral hemispheric cerebral lesions
Authors: Pierrot‐Deseilligny Charles , Rivaud Sophie , Penet Christiane , Rigolet Marie‐Hélène
Published: January 2005

Latencies of lateral visually guided saccades were studied in 60 patients without hemianopia who had unilateral focal lesions clearly visible on computed tomographic (CT) scan that were variously located in both cerebral hemispheres. Significantly asymmetrical latencies were found in 29 patients whose lesions had damaged the deep and posterior frontal region near the corpus callosum and/or, just inferior to this region, the anterior part of the internal capsule. In the 31 other patients, including those with lesions of the frontal eye fields (FEF), latencies were not significantly asymmetrical and the lesions spared the entire region just described. These topographical features suggest that the asymmetry of latencies is due to damage in a certain portion of the efferent pathways descending from the FEF. A significant increase in bilateral latency was observed in most patients whose lesions had damaged the posterior part of the parietal cortex and/or the underlying white matter. The parietal lobe could therefore exert an excitatory bilateral action on the triggering of visually guided saccades, probably mediated via the superior colliculus. A significant decrease in the bilateral or ipsilateral latency was often found in patients whose lesions had damaged the FEF or the underlying white matter. The frontal lobe could therefore exert a predominantly inhibitory bilateral action on this triggering, probably also mediated via the superior colliculus. However, an increase in contralateral latency in some patients with subcortical frontal lesions indicates that FEF also probably have an excitatory action. This action could be transmitted directly (or indirectly via the superior colliculus) to the reticular premotor structures by tracts decussating partly through the corpus callosum.
Cortical blindness: Etiology, diagnosis, and prognosis
Authors: Aldrich Michael S. , Alessi Anthony G. , Beck Roy W. , Gilman Sid
Published: January 2005

We examined 15 patients with cortical blindness, reviewed the records of 10 others, and compared these 25 patients to those in previous studies of cortical blindness. Although cerebrovascular disease was the most common cause in our series, surgery, particularly cardiac surgery, and cerebral angiography were also major causes. Only 3 patients denied their blindness, although 4 others were unaware of their visual loss. Electroencephalograms (EEGs) were performed during the period of blindness in 20 patients and all recordings were abnormal, with absent alpha rhythm. Visual evoked potentials recorded during blindness were abnormal in 15 of 19 patients, but did not correlate with the severity of visual loss or with outcome. Bioccipital lucencies were found in computed tomographic (CT) scans of 14 patients; none of the 14 regained good vision. Recovery of vision was poor in all 8 patients who had a spontaneous stroke, but fair or good in 11 of the other 17 patients. Prognosis was best in patients under the age of 40 years, in those without a history of hypertension or diabetes mellitus, and in those without associated cognitive, language, or memory impairments. We conclude that (1) the prognosis in cortical blindness is poor when caused by stroke; (2) EEGs are more useful than visual evoked potentials for diagnosis; and (3) bioccipital abnormalities shown on CT scan are associated with a poor prognosis.
Brain extraction of a calcium channel blocker
Authors: Grotta James C. , Pettigrew L. Creed , Lockwood Alan H. , Reich Catherine
Published: January 2005

Dihydropyridine calcium channel blockers may be effective treatment for acute cerebral ischemia, but the uptake of these drugs into the brain is unknown. A 0.2‐ml bolus of [14C]nicardipine hydrochloride and [3H] water was injected into the common carotid arteries of 7 normal and 7 ischemic rats. The corrected first‐pass extraction of nicardipine, compared to water, was calculated to be 30.7% into the hemispheres and 42.3% into the hippocampi. The uptake was greater into the ischemic hemispheres (p ≤ 0.001). These data suggest that dihydropyridines are available to binding sites and calcium channels in neurons.
Pontine ataxic hemiparesis studied by a high‐resolution magnetic resonance imaging system
Authors: Nabatame Hidehiko , Fukuyama Hidenao , Akiguchi Ichiro , Kameyama Masakuni , Nishimura Kazumasa , Torizuka Kanji
Published: January 2005

Using a high‐resolution magnetic resonance imaging system, we studied 3 patients who had exhibited pontine ataxic hemiparesis. In each patient, the ischemic lesions responsible for the contralateral ataxia were located in the dorsomedial basis pontis. The isointensity bands in the ischemic area on T2‐weighted images showed the spared transverse fibers originating from the contralateral pontine nuclei, and this may explain the cause of the unilateral ataxia.
Linkage of adrenoleukodystrophy to a polymorphic DNA probe
Authors: Aubourg Patrick R. , Sack George H. , Meyers Deborah A. , Lease John J. , Moser Hugo W.
Published: January 2005

Linkage studies between X‐linked adrenoleukodystrophy and a cloned deoxyribonucleic acid fragment (St14), which detects polymorphisms in the distal end of the long arm of the X chromosome (Xq27–28), have shown no recombination in six families. The lod score for these data (and another kindred reported earlier) [2] is 13.766 at recombination fraction (θ) = 0.0. These data permit assignment of adrenoleukodystrophy carrier status in family members at risk, supplementing the chemical measurement of very‐long‐chain fatty acids.
Reversible and irreversible nodal dysfunction in diabetic neuropathy
Authors: Brismar Tom , Sima Anders A. F. , Greene Douglas A.
Published: January 2005

Acute reversible diabetic nerve dysfunction has been associated with a reversible myo‐inositol–related (Na+ + K+)‐ATPase defect, while poorly reversible chronic nerve dysfunction correlates with progressive axoglial dysjunction of peripheral nerve. The causal relationships between biochemical and neuroanatomical abnormalities and those of nodal membrane function are not known. Nodal clamp examinations were carried out in the sciatic nerve of diabetic BB‐rats to elucidate the events underlying diabetic nerve dysfunctions and how these relate to metabolic and structural defects of diabetic nerve. With increasing duration of diabetes, there was a progressive decline in nodal action potentials attributable to decreased Na+ permeability and a decrease in the membranous Na+ gradient. Vigorous insulin therapy in short‐term (6‐week) diabetic BB‐rats normalized the Na+‐permeability defect and the membranous Na+ gradient. These defects did not reverse in long‐term (24‐week) diabetic animals subjected to the same treatment. This poorly reversible nodal dysfunction accounts for the not readily reversible conduction defect in chronic diabetes and is probably directly related to irreversible axoglial dysjunction.
Disorders of the autonomic nervous system: Part 2. investigation and treatment
Authors: McLeod J. G. , Tuck R. R.
Published: January 2005

Autonomic function may be adequately tested with noninvasive tests of sympathetic and parasympathetic pathways, including: the response of blood pressure to change in posture and isometric contraction, heart rate response to standing, variation in heart rate with respiration, Valsalva ratio, sweat tests, and plasma noradrenaline measurements. Abnormal results in two or more of these tests indicate autonomic dysfunction. Intraarterial catheterization and tests of vasomotor function are usually required only in doubtful cases or for research purposes. Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension. Orthostatic hypotension is best treated with physical measures, pharmacologically with 9‐alpha‐fluorohydrocortisone and dihydroergotamine mesylate. A number of other agents may be tried but results have been less effective.
Protective effects of liposome‐entrapped superoxide dismutase on posttraumatic brain edema
Authors: Chan Pak Hoo , Longar Susan , Fishman Robert A.
Published: January 2005

Oxygen‐derived free radicals and membrane lipid peroxidation have been postulated to be involved in brain edema and cell death, secondary to ischemia and traumatic injury. Using a model of brain edema induced by cold‐induced injury, we have demonstrated an early elevation of superoxide radicals followed by permeability changes in the blood‐‐brain barrier and development of edema in injured brain. Intravenous injection of liposome‐entrapped copper‐zinc‐‐superoxide dismutase 5 minutes before the injury‐enhanced entry of the enzyme into endothelial cells of the blood‐‐brain barrier of injured brain reduced the brain level of superoxide radicals and ameliorated blood‐‐brain barrier permeability changes and brain edema. Identical treatment 5 minutes after injury was also effective. These data demonstrate that superoxide radicals play an important role in the delayed development of vasogenic brain edema following brain injury.
Axilla skin biopsy: A reliable test for the diagnosis of Lafora's disease
Authors: Busard H. L. S. M. , GabreëLs‐Festen A. A. W. M. , Renier W. O. , Gabreës F. J. M. , Stadhouders A. M.
Published: January 2005

Skin biopsies from the axilla were examined in 7 patients with clinical signs and symptoms of lafora's disease, in 9 relatives (7 parents and 2 siblings), and in 17 patients with chronic or progressive degenerative neurological disorders and chronic epilepsy, who served as controls. In the biopsies of all patients with Lafora's disease, typical periodic acid‐Schiff (PAS)‐positive inclusions were present in the myoepithelial cells of the secretory acini of the apocrine glands and/or in the cells of the eccrine duct. No abnormalities were found in the biopsies from relatives and controls. We conclude that axilla skin biopsy is an easy and reliable test for diagnosing Lafora's disease, and is preferable to liver biopsy, but has no value for carrier detection.
Multi‐center study of Parkinson mortality with early versus later dopa treatment
Authors: Diamond Shirley G. , Marchkham Charles H. , Hoehn Marchgaret M. , McDowell Fletcher H. , Muenter Manfred D.
Published: January 2005

Four geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person‐years of observation, Group 1 had an observed‐to‐expected mortality ratio of 1.43; Group 2,2.44; and Group 3, 2.95 (p < 0.05). This result confirmed that increased duration of disease was associated with increased mortality risk. To examine the effect of the time of initiation of dopa treatment, duration of disease was held constant at 17 years for all three groups. Observed‐to‐expected mortality ratios were 1.43 for Group 1; 2.66 for Group 2; 2.63 for Group 3. This statistically significant advantage for Group 1 (p < 0.0001) led to the conclusion that early treatment with dopa has a beneficial effect on life expectancy. After 17 years of disease, causes of death in Group 1 were less likely (p = 0.027) to be due to Parkinson's disease than was found in the other groups.
Muscle energy metabolism in human phosphofructokinase deficiency as recorded by 31P nuclear magnetic resonance spectroscopy
Authors: Argov Zohar , Bank William J. , Marchis John , Leigh John S. , Chance Britton
Published: January 2005

31P nuclear magnetic resonance studies of a patient with phosphofructokinase deficiency in muscle provided the following new findings: First, ATP metabolism is disturbed at rest and during exercise. At rest, ATP levels are lower than normal and continue to decline during exercise. Second, exercise kinetics are normal, suggesting a normal mitochondrial fuel supply although glycolysis is blocked. Third, no “phosphate trapping” is observed during prolonged low‐level exercise. Fourth, postexercise recovery is abnormally prolonged by the slow dephosphorylation of sugar phosphates, which has an in vivo half‐life of about nine minutes. These findings demonstrate how musclé tissue adapts to a block in a major bioenergetic pathway.
Lambert‐Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones
Authors: Fukuoka Tadahiro , Engel Andrew G. , Lang Bethan , Newsom‐Davis John , Prior Christopher , W.‐Wray Denis
Published: January 2005

In the freeze‐fractured presynaptic membrane of the motor end‐plate, the active zones consist of two parallel arrays and each array contains 10‐ to 12‐nm particles arranged in two rows. In the Lambert‐Eaton myasthenic syndrome (LEMS) and in mice treated with 10 mg/day of LEMS IgG, administered intraperitoneally for several weeks, there was a paucity and disorganization of the active zones, and clusters of 10‐ to 12‐nm particles appeared. To further define the changes in the active zones, mice were studied that had been treated over 2 days with 104 to 180 mg of IgG. Treatment transferred the physiological defect of LEMS. Control mice received normal human IgG or no IgG. The spacing and density (number/unit area) of active‐zone particles were evaluated in presynaptic membrane P‐faces using computer‐assisted stereometry. In the normal active zone, the distance between particles in a given row and between adjacent rows of an array was less than, but the distance between the two arrays was greater than, the distance between the two antigen‐binding sites on human IgG. In mice treated with LEMS IgG, the initial alteration in the active zone was a Decemberrease in the distance between particles in a given row and between adjacent rows of an array; the distance between the two arrays remained unaltered. In more affected active zones, the parallel orientation of the rows was disturbed and the arrays became clusters. There was a significantly reduced density of active zones and of large‐membrane particles associated with all active zones and clusters. The findings are consistent with the idea that LEMS IgG binds to the active‐zone particles, cross‐links these particles, and then modulates their density. This interpretation is in agreement with findings of the companion paper which follows in this issue of the Annals in which we immunolocalized LEMS IgG to the active zones at the motor end‐plates.
Acetylcholine receptors in human thymic myoid cells in situ: An immunohistological study
Authors: Schluep Myriam , Willcox Nicholas , Vincent Angela , Dhoot Gurtej K. , Newsom‐Davis John
Published: January 2005

Myoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti–troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR). The myoid cells were rare and located mainly in the medulla, and most were clearly positive for AChR; labeling was similar with four individual monoclonal antibodies specific for extrajunctional AChR and five that also recognize endplate AChR. They were mostly keratin‐positive and consistently HLA–DR–negative. In the myasthenia gravis samples, the myoid cells were similar but largely confined to medullary epithelial areas; AChR labeling was slightly weaker, but otherwise they did not differ noticeably from those of control subjects. A preliminary finding was of even rarer AChR‐positive/HLA‐DR–positive antigen‐presenting (possibly) cells seen in 9 of 9 myasthenia gravis samples and in none of 9 control samples. Although myoid‐cell AChR appears antigenically similar to extrajunctional muscle AChR, and must therefore express the epitopes that myasthenics' antibodies recognize, these cells do not appear to be foci of immunological stimulation in myasthenia gravis.
Trends in the incidence rates of stroke in Rochester, Minnesota, since 1935
Authors: Homer Daniel , Whisnant Jack P. , Schoenberg Bruce S.
Published: January 2005

The Mayo Clinic medical records system and records‐linkage system have been used to study trends in the incidence of stroke in Rochester, Minnesota, for comparison with U.S. stroke mortality trends. This study extends the observations back through 1935. The average annual incidence rate for the period 1935 to 1944 was 188 and 179 per 100,000 population for men and women, respectively—not significantly different from 200 for men and 178 for women for the period 1945 to 1954. The blood pressure level in these patients did not affect probability of survival or recurrent stroke. The trend in the incidence rate of stroke for women showed no change for the 20 years from 1935 to 1954, after which there was a gradual Decemberline. For men there was little change until 1969, after which there was a sharp Decemberline. We suggest that the gradual Decemberline in U.S. stroke mortality rates for this early period may include an artifact introduced by changing codes and changing fashions of diagnosis.
Photic cortical reflex myoclonus
Authors: Shibasaki Hiroshi , Neshige Ryuji
Published: January 2005

Three patients with flash‐evoked myoclonus were studied electrophysiologically. Myoclonic jerks were elicited at a fixed latency after the application of photic stimuli and were always preceded at a fixed time interval by extremely enhanced cortical evoked potentials. The enhanced electroencephalographic (EEG) responses to flash were widely distributed over the scalp and were maximal at the central region; the occipital response preceded the frontocentral response by 3.4 to 5.1 msec. The interval from the frontocentral EEG response to the flash‐evoked myoclonus was similar to that from the giant somatosensory evoked potential to the electrically evoked myoclonus. Investigation of recovery of evoked cortical responses and of myoclonic jerks showed a period of extremely enhanced excitability of both central and peripheral phenomena following stimulus. All of these findings suggest a cortical reflex mechanism. The role of the occipital cortex in the pathogenesis of photic cortical reflex myoclonus remains to be elucidated.
Effects of oral physostigmine in Alzheimer's disease
Authors: Stern Yaakov , Sano Mary , Mayeux Richard
Published: January 2005

Previous studies of oral physostigmine in the treatment of Alzheimer's disease have: (1) assumed physostigmine is effective only in mildly affected patients; (2) relied on an initial “dose‐finding” phase to determine the most effective dose and excluded nonresponders; and (3) primarily assessed memory. We examined the response of 22 patients to six different daily dosages of oral physostigmine, using selective reminding tests that were administered twice daily. Nine patients had a “best” dose/day (mode = 13 mg/day), which was used in a subsequent double‐blind crossover study. The otehr 13 were given the highest tolerated dose. The selective reminding test and a full neuropsychological battery were given during the drug and placebo periods. As a group, the 22 patients improved significantly on the Wechsler Adult Intelligence Scale—Revised Digit Symbol subtest and a shape cancelation task (p < 0.05). Nine patients showed improved performance on the selective reminding test during physostigmine treatment, and 9 showed no response; 4 patients performed better during placebo treatment. Dose finding did not help in predicting response in the crossover study; only 2 of the 9 who showed improvement had a best dose. Dementia severity did not predict corssover response. This suggests that: (1) physostigmine as administered had no pronounced effect on memory in Alzheimer's disease; (2) oral physostigmine produces no greater benefits on memory in mildly than in moderately demented patients; (3) response in a dose‐finding phase does not predict response in double‐blind crossover; and (4) Digit Symbol and cancelation tasks may be more sensitive than memory tests to the effects of oral physostigmine.
Acute ischemia causes axonal stasis, swelling, attenuation, and secondary demyelination
Authors: Nukada Hitoshi , Dyck Peter James
Published: January 2005

Microsphere embolization of rat sciatic nerve capillaries results in a central fascicular ischemic core. Twenty‐four hours after microembolization, the pathological alterations along the length of 55 myelinated fibers were reconstructed by computer imaging of 2,000 serial semi‐thin epoxy sections of a tissue block that extended from just above and into an ischemic core. From proximal to distal, the typical sequence of pathological alternations was: normal → swollen dark axons + thin myelin or demyelination → attenuated axons → axon cytolysis (46 fibers) or normal axons (9 fibers). Because organelle accumulation and axonal swelling were the earliest and most proximal pathological lesions, we infer that regional hypoxia causes axonal stasis as a primary event. Demyelination was found in fibers showing swollen dark and attenuated axons. These findings suggest that axons are selectively vulnerable to acute ischemia and that, depending on severity, the fibers either undergo axonal degeneration or transitory structural alterations without axonal degeneration, the latter consisting of axonal changes and secondary demyelination.
Experimental hemiplegia in the monkey: Basal ganglia glucose activity during recovery
Authors: Gilman Sid , Dauth George W. , Frey Kirk A. , Penney John B.
Published: January 2005

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a dense contralateral hemiplegia that recovers partially with time. During the phase of dense hemiplegia, the local cerebral metabolic rate for glucose (lCMRGlc) is decreased significantly in the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus of the hemisphere ipsilateral to the lesion. In the present study, lCMRGlc in the basal ganglia was studied during the phase of partial recovery of motor activity. lCMRGlc was partially restored, and the greatest degree of restoration occurred in structures with direct connections to the cerebral cortex (caudate nucleus, putamen, subthalamic nucleus, substantia nigra, and red nucleus). Restoration was least in structures that do not receive direct connections from the cerebral cortex (the internal and external segments of the globus pallidus). The findings support the hypothesis that corticofugal activity accounts for a substantial degree of functional recovery.
Myelin‐associated glycoprotein in multiple sclerosis lesions: A quantitative and qualitative analysis
Authors: Möller Johanna R. , Yanagisawa Katsuhiko , Brady Roscoe O. , Tourtellotte Wallace W. , Quarles Richard H.
Published: January 2005

Myelin‐associated glycoprotein (MAG), myelin basic protein (MBP), and proteolipid protein (PLP) were quantitated by immunoassays in nine plaque, inner periplaque, outer periplaque, and normal‐appearing white matter regions from brains of five multiple sclerosis patients and compared with the levels found in white matter samples of control subjects matched for age, postmortem time, and brain region. In plaque and inner periplaque regions, all three proteins were substantially reduced due to extensive myelin loss. In outer periplaque regions, MBP and PLP were close to control levels, but MAG was significantly reduced to a mean of 57% of control. All three proteins were close to control levels in the normal‐appearing white matter samples. MAG in the various regions was qualitatively examined on Western blots by binding of lectins and by immunostaining with polyclonal and monoclonal antibodies against carbohydrate and protein epitopes of MAG. Densitometric scanning of these blots did not reveal any qualitative differences in the oligosacharide or polypeptide moieties of MAG between samples from control subjects and those from multiple sclerosis patients. However, a high proportion of the MAG in the multiple sclerosis samples was often in the form of dMAG, a proteolytic derivative of MAG that is formed by a myelin‐associated, Ca2+‐activated, neutral protease. The preferential loss of MAG at the periphery of multiple sclerosis plaques may be initiated by its proteolytic conversion to dMAG.
Positron emission tomography study of human brain functional development
Authors: Chugani Harry T. , Phelps Michael E. , Mazziotta John C.
Published: January 2005

From over 100 children studied with 2‐deoxy‐2{18F}fluoro‐D‐glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 μmol/min/100 gm), and rapidly rose to reach adult values (19 to 33 μmol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 μmol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to Decemberline, and reached adult rates again by the latter part of the second Decemberade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.
On‐off phenomenon: Relation to levodopa pharmacokinetics and pharmacodynamics
Authors: Nutt John G.
Published: January 2005

Motor function in the moderately to severely affected parkinsonian patient is critically dependent upon delivery of levodopa to the striatum. This, in turn, is influenced by the fluctuating plasma concentrations of levodopa produced by the drug's short half‐life and erratic absorption, and by modifiable transport at the blood‐brain barrier. Duration of response to a single dose of levodopa is proportional to peak plasma drug levels, and paradoxical responses may occur when plasma concentrations are in the vicinity of minimum effective concentrations. Thus the strategy of administering frequent, small doses of levodopa may contribute additional unpredictability to a fluctuating clinical response imposed by pharmacokinetic factors.
Differences in cerebral blood flow and glucose utilization in vegetative versus locked‐in patients
Authors: Levy David E. , Sidtis John J. , Rottenberg David A. , Jarden Jens O. , Strother Stephen C. , Dhawan Vijay , Ginos James Z. , Tramo Mark J. , Evans Alan C. , Plum Fred
Published: January 2005

Positron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked‐in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 ± 0.13 (mean ± SEM) mg/100 gm/min, less than half the normal value of 6.82 ± 0.23 (p < 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked‐in patients was 5.08 ± 0.69, a 25% reduction (p < 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain.
Cerebrospinal fluid cholinesterases in aging and in dementia of the alzheimer type
Authors: Atack John R. , May Conrad , Kaye Jeffrey A. , Kay Arthur D. , Rapoport Stanley I.
Published: January 2005

Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20–86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age‐related increase in CSF protein and AChE activity and a significant correlation (p < 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean ± SD = 17.5 ± 3.6 and 15.3 ± 4.4 nmol/min/ml, respectively) were significantly lower (p < 0.05) than in 13 age‐matched control subjects (21.5 ± 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p < 0.05) in subjects with an early onset compared to those with a late onset (16.4 ± 3.4 and 19.7 ± 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18‐month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.
Fiber pathways of cortical areas mediating smooth pursuit eye movements in monkeys
Authors: Tusa Ronald J. , Ungerleider Leslie G.
Published: January 2005

Recent studies in rhesus monkeys and human patients have increased our understanding of the role of various cortical regions in the generation of smooth pursuit eye movements. Little is known, though, about the cerebral white matter pathways mediating smooth pursuit. In this paper, we describe both the corticocortical and corticosubcortical projections from areas in the monkey brain known to be involved in smooth pursuit. The corticocortical pathways within one hemisphere consists of a sequence of arcuate fiber bundles interconnecting (1) striate cortex with an area in occipitoparietal cortex called the middle temporal (MT) area, (2) area MT with two areas in parietal cortex called the medial superior temporal (MST) and posterior parietal (PP) areas, and (3) area MST with area PP. An interhemispheric pathway interconnecting areas MT and MST consists of fibers sequentially passing through the tapetum, major forceps, and the splenium of the corpus callosum. The corticosubcortical pathway from area MST to the pontine nuclei and accessory optic system consists of fibers sequentially running through the internal sagittal stratum, the retrolenticular part of the internal sagittal stratum, and the cerebral peduncle. Based on the effects of lesions on pursuit eye movements, these corticocortical and corticosubcortical projections can be divided into sensory, motor, and attentional/spatial systems. Evidence from clinical studies suggests that homologous systems exist in the human cerebrum.
Deficiency of subunits of complex I and mitochondrial encephalomyopathy
Authors: Ichiki Takashi , Tanaka Masashi , Nishikimi Morimitsu , Suzuki Hiroshi , Ozawa Takayuki , Kobayashi Masanori , Wada Yoshiro
Published: January 2005

Enzymic activities of the respiratory chain and content of immunochemically detectable subunits in NADH‐ubiquinone oxidoreductase (Complex I) were measured in mitochondria from the skeletal muscles of 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The rotenone‐sensitive NADH‐cytochrome c reductase activity was extremely decreased, ranging from 0% to 27% of the control value. In all patients, the content of subunits of Complex I was also reduced in parallel with the rotenone‐sensitive NADH‐cytochrome c reductase activity. It is suggested that the variation in the degree of deficiency of Complex I subunits could explain the clinical heterogeneity of patients with MELAS.
The peripheral neuropathy of necrotizing arteritis: A clinicopathological study
Authors: Said Gérard , Lacroix‐Ciaudo Catherine , Fujimura Harustoshi , Blas Catherine , Faux Nelly
Published: January 2005

We have reviewed the clinical and morphological data from 100 patients with necrotizing arteritis in muscle and/or in nerve samples taken by biopsy. The neuropathy occurred in the context of a multisystem disorder (Group 1) or in apparent isolation (Group 2). The average age of patients was 59 in Group 1 and 61 in Group 2. Females were more commonly affected than males, especially in the first group. Necrotizing arteritis complicated the course of rheumatoid arthritis in 25 patients. In 3 patients necrotizing arteritis was associated with infection with the human immunodeficiency virus, the agent of AIDS. Tests for hepatitis B surface antigen were positive in 19 patients. Mononeuritis was present in 13, mononeuritis multiplex in 62, and distal symmetrical sensory or sensorimotor neuropathy in 19 patients. In both groups of patients, the muscle biopsy was more frequently diagnostic for arteritis than was the nerve biopsy (80% versus 55%). The average incidence of isolated fibers undergoing axonal degeneration was 64.8%; that of demyelinated/remyelinated fibers was 1.9%. We conclude that the combination of nerve and muscle sampling increases the chance of visualizing characteristic arterial lesions in vasculitic neuropathy.
Lesch‐nyhan syndrome: A study of motor behavior and cerebrospinal fluid neurotransmitters
Authors: Jankovic Joseph , Caskey Thomas C. , Stout J. Timothy , Butler Ian J.
Published: January 2005

We studied 5 boys, 2 to 10 years old, with marked or complete deficiency of hypoxanthine‐guanine phosphoribosyltransferase and Lesch‐Nyhan syndrome with varying degrees of mental retardation, dysarthria, chorea, dystonia, spasticity, and ataxia. Four patients had marked reduction of homovanillic acid in the cerebrospinal fluid (CSF) and all showed low CSF 3‐methoxy‐4‐hydroxy phenylethylene glycol, indicating reduced dopamine and norepinephrine turnover. Three patients showed high CSF 5‐hydroxyindoleacetic acid, suggesting increased serotonin turnover. Some patients improved with carbidopa‐levodopa, but others benefited from tetrabenazine, a monoamine‐depleting agent. This study provides support for the theory of abnormal central monoamine metabolism in Lesch‐Nyhan syndrome.
Peripheral neuropathy in the acquired immunodeficiency syndrome
Authors: de La Monte Suzanne M. , Gabuzda Dana H. , Ho David D. , Brown Robert H. , Hedley‐Whyte E. Tessa , Schooley Robert T. , Hirsch Martin S. , Bhan Atul K.
Published: January 2005

The histopathological and immunopathological features of peripheral neuropathy were investigated in 21 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS‐related complex (ARC). Clinical syndromes observed in the 11 (52%) symptomatic patients included distal symmetrical polyneuropathy (DSPN) and chronic inflammatory demyelinative polyneuropathy (CIDP). Specimens from 19 of 20 patients (95%), both symptomatic and asymptomatic, had histopathological evidence of moderate or severe demyelination (79%), axonal degeneration (36%), and mononuclear cell inflammation (37%). Nerves from patients with CIDP and DSPN showed similar degrees of demyelination and axonal degeneration, but inflammation was more intense in CIDP. Immunohistochemical staining identified the majority of inflammatory cells as T lymphocytes or macrophages, with a predominance of CD8+ cytotoxic/suppressor cells. Diffuse immunostaining for human leukocyte antigen (HLA)‐DR was present on endothelial cells, mononuclear inflammatory cells, and Schwann cells, and variable patchy immunostaining for HLA‐DR was present on nerve fibers. Control nerve specimens showed staining for HLA‐DR limited to endothelial, and a few mononuclear, cells. The patterns of immunostaining were similar for AIDS and ARC patients. Human immunodeficiency virus (HIV) was cultured from peripheral nerve in 3 patients, but HIV antigen was not detected by immunohistochemical staining of 8 specimens. The findings implicate HIV infection in nerve, with T cell‐ and macrophage‐mediated tissue destruction as the pathogenetic mechanism of the AIDS/ARC neuropathy.
Brain injury, handedness, and speech lateralization in a series of amobarbital studies
Authors: Woods Roger P. , Dodrill Carl B. , Ojemann George A.
Published: January 2005

Data on handedness and speech lateralization in patients selected for amobarbital studies have frequently been extrapolated to the normal population, despite the high frequency of brain injuries which might alter lateralization in these patients. To achieve a better definition of the relationships between brain injury, handedness, and speech lateralization, we reviewed the records of 237 consecutive patients who underwent amobarbital testing. Brain injuries sufficient to cause right hemiparesis were strongly associated with left handedness and atypical (right hemisphere or bilateral) speech representation. Among nonhemiparetic patients, abnormal extratemporal radiological findings were associated with an increased incidence of left handedness and atypical speech lateralization. It was not possible to demonstrate any alteration in handedness or speech representation resulting from abnormalities restricted to the temporal lobes, although such alterations could not be excluded. Handedness and speech lateralization established using amobarbital studies in neurosurgical patients may not be representative of the normal population.
Acute fulminating fatal leukoencephalopathy as the only manifestation of human immunodeficiency virus infection
Authors: Jones H. Royden , Ho David D. , Forgacs Pierre , Adelman Lester S. , Silverman Mark L. , Baker Richard A. , Locuratolo Patricia
Published: January 2005

A case of acute human immunodeficiency virus (HIV) infection manifested by a rapidly fulminating, necrotizing, demyelinating encephalopathy that led to brain death in 5 days is reported. Autopsy demonstrated predominant white matter lesions, acute neuronal damage, and scanty cellular response. Cultures of cerebrospinal fluid were positive for HIV, suggesting an acute infection.
Somatostatin and neuropeptide Y concentrations in pathologically graded cases of huntington's disease
Authors: Beal M. Flint , Mazurek Michael F. , Ellison David W. , Swartz Kenton J. , McGarvey Usha , Bird Edward D. , Martin Joseph B.
Published: January 2005

Somatostatin and neuropeptide Y concentrations have previously been reported to be increased in the basal ganglia in Huntington's disease (HD). In the present study we have extended these findings by examining both somatostatin‐like immunoreactivity (SLI) and neuropeptide Y–;like immunoreactivity (NPYLI) in cases of HD, which were graded according to the severity of pathological degeneration in the striatum. In addition, we surveyed a large number of subcortical nuclei and cortical regions for alternations. Both SLI and NPYLI were significantly increased about threefold in the caudate, putamen, and the nucleus accumbens. Increases in mild and severe grades were similar, which is consistent with a relative but not absolute sparing of striatal aspiny neurons in which somatostatin and neuropeptide Y are colocalized. Significant increases of NPYLI were also found in the external pallidum, subthalamic nucleus, substantia nigra compacta, claustrum, anterior and dorsomedial thalamus, bed nucleus of the stria terminalis, and locus ceruleus. SLI was significantly increased in the external pallidum, red nucleus, and locus ceruleus. Measurements of both neuropeptides were made in 24 regions of the cerebral cortex. Significant increases in both NPYLI and SLI were found in the frontal cortex (Brodmann areas 6, 8, 9, 10, 11, and 45) and temporal cortex (Brodmann area 21), whereas NPYLI was also increased in Brodmann areas 12, 20–22, 25, and 42. Alterations in the cerebral cortex were as pronounced in cases with mild striatal pathological changes as in those with severe striatal pathological changes. These alterations may occur early in HD and could reflect a selective sparing of somatostatin–neuropeptide Y cortical neurons combined with cortical atrophy. The findings are consistent with a possible role for an excitotoxin in the pathogenesis of HD.
Prospective intellectual testing in children with brain tumors
Authors: Duffner Patricia K. , Cohen Michael E. , Parker Mitchell S.
Published: January 2005

Sixteen children with brain tumors received prospective intellectual evaluations with a follow‐up of 2 to 5 years. All patients were treated with surgery and radiation and 5 received chemotherapy. Most of the children remained within the normal range of intelligence, but intelligence quotient (IQ) scores declined over time. Learning disabilities were present in 15 of 16 children after radiation, and 11 required special educational services. Risk factors associated with decline in IQ appear to be young age at time of radiation and adjuvant chemotherapy.
Lack of association between essential tremor and Parkinson's disease
Authors: Cleeves Lynn , Findley Leslie J. , Koller William
Published: January 2005

Four aspects of a possible association between essential tremor (ET) and Parkinson's disease (PD) were investigated: (1) the frequency of extrapyramidal signs in ET; (2) the frequency of concurrent ET and PD (i.e., monosymptomatic postural tremor for 5 or more years prior to onset of PD); (3) the frequency of ET in the families of PD patients; and (4) the frequency of PD in families of ET patients. Two hundred and thirty‐seven ET patients (137 in London and 100 in Chicago) were evaluated. One hundred patients with PD and 100 normal control subjects were also investigated. Mild extrapyramidal signs occurred in only 4.5% of ET patients and were consistent with those found in normal aging. Only 3% of PD patients gave a history of uncomplicated ET. There was no difference in the frequency of a family history of PD between ET patients, a group of PD patients, and control subjects. Frequency of a family history of ET was higher among PD patients than control subjects, although the difference was not statistically significant. These data indicate that there is no association or genetic link between ET and PD.