bluuebunny/crossref_metadata_2025 huggingface dataset:
Borderzone infarctions distal to internal carotid artery occlussion: Prognostic implications
Authors: Bogousslavsky J. , Regli F.
Published: January 2005

Bilateral watershed (WS) infarction at the borderzone of the middle cerebral artery territory are typically related to severe hypotensive events. Unilateral WS infarctions have sometimes been reported in occlusion of the ipsilateral internal carotid artery (ICA), but their pathogenesis and prognostic implications are poorly known. Twenty‐six of 154 (17%) consecutive patients with ICA occlusion had a computed tomography–proved ipsilateral WS infarct. Severe active heart disease with hypotension and syncope (p < 0.0001), severe contralateral ICA disease (p < 0.001), and elevated venous hematocrit values (p < 0.001) related to heavy smoking were more frequent in the patients with WS infarction than in other patients. Delayed infarctions in the territory of the main branches of the middle cerebral artery distal to the ICA occlusion correlated with a visible stump or emboligenic changes (ulcerated or irregular stenosis) on the collateral channels, but this was not true for delayed WS infarctions. These findings suggest that most of the WS infarctions were hemodynamic. The patients with WS infarct had a higher death rate (9.9% per year) than did the patients without WS infarct (2.3% per year), suggesting that heart disease should be particularly closely managed in patients with WS infarctions. As WS infarctions were the most frequent type of infarction distal to an occluded ICA, appropriate treatment of all potential causes of systemic hemodynamic disturbances may be crucial in the long‐term management of patients with ICA occlusion.
Bilateral lucency of the globus pallidus complicating methylmalonic acidemia
Authors: Korf Bruce , Wallman James K. , Levy Harvey L.
Published: January 2005

A child was seen because of encephalopathy and metabolic ketoacidosis at 19 months. She was found to have a cobalamin‐responsive form of methylmalonic acidemia of the cbl A complementation group. However, after treatment with cyanocobalamin and a protein‐restricted diet, with recovery from the encephalopathy, she was found to have a tremor and bilateral dystonic posturing in association with lucencies in the globus pallidi shown by computed tomographic scan.
Saccadic eye movement dysfunction in Alzheimer's disease
Authors: Fletcher William A. , Sharpe James A.
Published: January 2005

Saccades were measured by magnetic search coil technique in 13 patients with Alzheimer's disease and compared with those of 11 age‐matched control subjects. We analyzed responses to target motion of predictable and unpredictable timing or amplitude, and responses to briefly flashed targets. Latencies were significantly prolonged and peak velocities reduced only when the timing of target motion was unpredictable. Saccades to predictable amplitude targets were abnormally hypometric. In 8 patients, impersistence of gaze was manifested by large‐amplitude saccadic intrusions away from the intended position of gaze. When instructed to make saccades away from a flashed target, patients made reflexive saccades toward the target. We attribute this visual grasp reflex to frontal lobe degeneration. These eye movement deficits can be used to quantify motor dysfunction in Alzheimer's disease.
Neurofibrillary degeneration of cholinergic and noncholinergic neurons of the basal forebrain in Alzheimer's disease
Authors: Rasool C. G. , Svendsen Clive N. , Selkoe Dennis J.
Published: January 2005

Two principal features of Alzheimer's disease (AD) are (1) the occurrence of neurofibrillary tangles (NFTs) and senile plaques, and (2) the loss of cortical cholinergic activity because of dysfunction of neurons in the basal forebrain cholinergic system. The relationship of these two abnormalities is an unresolved issue in the pathology of AD. We used polyclonal antibodies specific for paired helical filaments (PHFs), combined with acetylcholinesterase (AChE) histochemistry, to assess the cytoskeletal changes of cholinergic and noncholinergic neurons in the basal forebrain in AD. In both sporadic and familial AD, the nucleus basalis of Meynert (nbM) showed a marked decrease in AChE‐positive (AChE+) perikarya and abundant immunoreactive NFTs. In double‐labeling studies of the nbM, PHF reactivity was found both in surviving AChE+ neurons and in many AChE− NFTs that were not associated with microscopically recognizable cell structures. Some surviving AChE+ perikarya did not contain NFTs. Numerous NFTs and senile plaques were identified by PHF immunoreactivity in other basal forebrain areas, including subnuclei of the amygdala that showed low or absent AChE activity. We conclude that (1) the dysfunction and death of cholinergic neurons in the nbM is associated with extensive NFT formation, including apparently residual NFTs in loci where nbM neurons once existed; and (2) many noncholinergic neurons and neurites in the basal forebrain show NFT and senile plaque formation. The cytopathology of AD involves neurons of varying transmitter specificities, including cholinergic neurons in the basal forebrain.
Widespread reduction of somatostatin‐like immunoreactivity in the cerebral cortex in Alzheimer's disease
Authors: Beal M. Flint , Mazurek Michael F. , Svendsen Clive N. , Bird Edward D. , Martin Joseph B.
Published: January 2005

Although several studies have documented reduced concentrations of somatostatin‐like immunoreactivity (SLI) in the cerebral cortex in Alzheimer's disease, there is controversy concerning the extent and importance of these changes. We measured SLI in brains obtained post mortem from 12 patients with pathologically confirmed Alzheimer's disease and from 13 neurologically normal controls. All major cortical and subcortical regions were examined. Widespread reductions of SLI in Alzheimer's disease cerebral cortex were found, with the most profound changes seen in temporal lobe; but there also were major reductions in both the frontal and occipital cortex. There were no significant reductions in subcortical regions. Characterization of SLI by high‐pressure liquid chromatography showed no significant difference in profiles between Alzheimer's disease and control frontal cortex. These results suggest that the reduction in somatostatin immunoreactivity in Alzheimer's disease may be caused by degeneration of intrinsic somatostatin cortical neurons.
X‐linked neuropathy: Gene localization with DNA probes
Authors: Fischbeck Kenneth H. , ar‐Rushdi Nada , Pericak‐Vance Margaret , Rozear Marvin , Roses Allen D. , Fryns J. P.
Published: January 2005

We used probes for DNA polymorphisms on the X chromosome to study genetic linkage in four families with X‐linked neuropathy. Despite clinical variability, all four families showed the same linkage pattern. We found evidence in each family of linkage to the marker DXYS1 on the proximal long arm of the X chromosome, as reported by others. We also found linkage to p58—1 (DXS14) on the proximal short arm. We found only loose linkage or nonlinkage to nine other markers located elsewhere on the chromosome. Our analysis places the gene defect for this disorder in the region of DXYS1 and p58—1, near the centromere of the X chromosome.
Creutzfeldt‐Jakob disease: Clinical analysis of a consecutive series of 230 neuropathologically verified cases
Authors: Brown Paul , Cathala Françoise , Castaigne Paul , Gajdusek D. Carleton
Published: January 2005

In this consecutive series of 230 patients with neuropathologically verified Creutzfeldt‐Jakob disease (CJD), the disease was found to affect men and women with approximately equal frequency in a peak plateau between the ages of 55 and 75 years (mean, 61.5 years). Familial cases accounted for 4 to 8% of the total series. Nonspecific prodromal symptoms occurred in one third of the patients, and the neurological presentation, although usually a gradually evolving mental deterioration, was of rapid onset in 20% of patients and in 36% of patients consisted exclusively of neurological symptoms. The great majority of these symptoms were of cerebellar or visual origin. Extrapyramidal muscular rigidity, myoclonus, and characteristic periodic electroencephalographic (EEG) complexes were observed comparatively late in the illness, and some type of involuntary movement or periodic EEG activity was seen in over 95% of the patients. The median duration of illness was 4 months (mean, 7.6 months); 90% of patients died within a year of onset.
A postmortem study of amino acid neurotransmitters in Alzheimer's disease
Authors: Ellison David W. , Beal M. Flint , Mazurek Michael F. , Bird Edward D. , Martin Joseph B.
Published: January 2005

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, γ‐aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high‐performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that γ‐aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process.
Incidence, clinical features, and prognosis in Bell's palsy, Rochester, Minnesota, 1968–1982
Authors: Katusic Slavica K. , Beard C. Mary , Wiederholt W. C. , Bergstralh Erik J. , Kurland Leonard T.
Published: January 2005

The average annual incidence of Bell's palsy per 100,000 population in Rochester, Minnesota, for 1968 through 1982 was 25.0 for both sexes combined; crude rates for males and females were 22.8 and 26.9, respectively, based on 85 males and 121 females. The relationship between various clinical features, patient characteristics, and the type of recovery was analyzed. In 206 patients, 28 (14%) experienced incomplete recovery and 178 (86%) had complete recovery, based on evidence in the medical records. Using logistic regression, complete facial weakness, non‐ear pain, and hypertension were identified as the most important risk factors for incomplete recovery. Patients were divided into two groups for comparison of treatment results; one group (n = 94) was without any of the three identified risk factors, and the other group (n = 112) consisted of patients who had one or more risk factors. Results suggested that among the latter group, those treated with steroids fared better than those in any of the other treatment groups.
Spontaneous vertical eye movements in coma
Authors: Rosenberg Michael L.
Published: January 2005

Patients in coma may exhibit several different types of spontaneous ocular movements. Three forms of spontaneous vertical movements have been distinguished based on the relative velocities of their downward and upward phases. The pathophysiological basis of all these movements has remained obscure. Two patients are reported who demonstrated all three types of spontaneous vertical movements (ocular bobbing, ocular dipping, and reverse ocular bobbing), implying that the movements may all be differing manifestations of the still unknown pathophysiological process.
Oculomasticatory myorhythrma: A unique movement disorder occurring in Whipple's disease
Authors: Schwartz Michael A. , Selhorst John B. , Ochs Alfred L. , Beck Roy W. , Campbell William W. , Harris J. Kim , Waters Barry , Velasco Manuel E.
Published: January 2005

We describe two patients and a previously reported patient who acquired unique pendular vergence oscillations of the eyes and concurrent contractions of the masticatory muscles, i.e., oculomasticatory myorhythmia (OMM). The smooth disjunctive eye movements cycled with a frequency of 0.8 to 1.2 Hz. An analysis of peak velocities (15 to 200 degrees/sec) with respect to peak amplitudes (5 to 25 degrees) revealed dynamics characteristic of normal vergence movements. The pathological alterations resulting in pendular vergence oscillations implicate a separately functioning, physiologically normal vergence system within the brainstem. In addition to paralysis of vertical gaze, each patient also experienced progressive somnolence and intellectual deterioration. An intestinal biopsy in 1 patient established a diagnosis of Whipple's disease, which led to appropriate treatment and amelioration of the OMM. A pathological diagnosis of Whipple's disease of the central nervous system was made in the other 2 patients; results of an intestinal biopsy in one of these patients were normal. No patient had palatal myoclonus, and olivary pseudohypertrophy was not found in two autopsy examinations. Thus, OMM is a distinct movement disorder and has been recognized only in Whipple's disease. We conclude that patients with OMM should be treated presumptively for Whipple's disease of the central nervous system, even if a jejunal biopsy is normal.
Correlates of early disability in Huntington's disease
Authors: Mayeux Richard , Stern Yaakov , Herman Andrew , Greenbaum Linda , Fahn Stanley
Published: January 2005

Functional disability in Huntington's disease usually results from a combination of the movement disorder, intellectual decline, and psychopathological changes, but the unique contribution of each element has never been investigated. The Shoulson‐Fahn functional capacity rating scale measures independence in such daily activities as eating, dressing, and managing personal finances, and is used to stage the illness and follow its progression. To determine which problems contribute most to reduced functional capacity as the disease evolves, we reviewed the records of 48 consecutive patients who were evaluated for intellectual and emotional status and motor disability. Each patient was staged and rated for functional capacity at the time of the examinations. Thirty‐three of these patients were followed over several years with repeat evaluations at 6‐month intervals. Intellectual impairment and depression correlated significantly with reduced functional capacity. However, when the somatic symptoms of depression were eliminated from the analysis, its relationship to functional capacity was no longer significant. Duration of illness, motor disability, and age at onset also had little impact. Neuropsychological test performance and functional capacity deteriorated over time. Our data suggest that intellectual impairment is a major factor in reducing functional capacity in the early stages of Huntington's disease.
Dicarboxylic aciduria in an infant with spinal muscular atrophy
Authors: Kelley Richard I. , Sladky John T.
Published: January 2005

A 1‐year‐old infant with classic Werdnig‐Hoffmann disease was found to excrete abnormally large amounts of dicarboxylic acids in both fed and fasting states, with especially notable increases in the longer‐chain (C10 and C12) 3‐hydroxydicarboxylic acids. Dicarboxylic aciduria has not previously been associated with Werdnig‐Hoffmann disease and suggests a primary or secondary defect of fatty acid metabolism in the disorder.
Reduced cerebral glucose metabolism and increased brain capillary permeability following high‐dose methotrexate chemotherapy: A positron emission tomographic study
Authors: Phillips Peter C. , Dhawan Vijay , Strother Stephen C. , Sidtis John J. , Evans Alan C. , Allen Jeffrey C. , Rottenberg David A.
Published: January 2005

Regional glucose metabolic rate constants and blood‐to‐brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high‐dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug‐induced alteration in blood–brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.
Posterior cerebral artery stenosis
Authors: Pessin Michael S. , Kwan Eddie S. , DeWitt L. Dana , Hedges Thomas R. , Gale Daniel , Caplan Louis R.
Published: January 2005

We analyzed the clinical features of symptomatic posterior cerebral artery (PCA) stenosis in 6 patients selected from 15 patients with angiographically documented PCA atherostenosis occurring during a 7‐year period. Transient ischemic attacks (TIAs) were the major presentation in 5 patients. A homonymous visual field defect was present in 2 patients. TIA symptoms were predominantly visual or sensory, or both. The most common visual symptom was difficulty seeing to one side. One patient saw flashing lights. Sensory spells were always paresthetic, usually involving the arm and hand and occasionally the face and leg. Three patients had visual and sensory spells together. Two patients with a visual field defect had calcarine infarcts found by computed tomography. All patients were treated with warfarin. During followup (4 months to 4 years), no patient had a new stroke in the PCA territory, and only one continued to have TIAs. PCA atherostenosis is rarer than PCA embolic occlusion. In contrast to those with PCA embolism, our patients with PCA atherostenosis had more TIAs and fewer infarcts. The clinical features of PCA stenosis—preponderance of visual and sensory TIAs‐distinguish this vascular lesion from stenosis of the middle cerebral artery.
Endemic tropical spastic paraparesis associated with human T‐lymphotropic virus type I: A clinical and seroepidemiological study of 25 cases
Authors: Vernant J. C. , Maurs L. , Gessain A. , Barin F. , Gout O. , Delaporte J. M. , Sanhadji K. , Buisson G. , De‐Thé G.
Published: January 2005

Tropical spastic paraparesis (TSP) is a common myeloneuropathy with primary and predominant involvement of the pyramidal tract and minimal sensory loss. The epidemic form of TSP is related to toxic nutritional factors, but the endemic form occurs in clusters in tropical areas, especially in India, Africa, the Seychelles, Colombia, and areas of the Caribbean. We describe the clinical and epidemiological features of 25 TSP patients from Martinique (French West Indies) with serum antibodies to human T‐lymphotropic virus type I (HTLV‐I). Furthermore, all 11 patients who were seropositive for HTLV‐I had specific HTLV‐I antibodies in their CSF. All were women. The age of onset varied from 25 to 60 years (mean, 45 years). The main clinical features are spastic paraparesis or paraplegia with spasticity of the upper limbs, minimal sensory loss, and bladder dysfunction. Minimal estimated incidence and prevalence are 1 per 100,000 inhabitants per year and 8 per 100,000, respectively. Seventeen percent of the relatives of patients with HTLV‐I–associated TSP have HTLV‐I antibodies (1 husband and 7 children). In Martinique, the prevalence of HTLV‐I antibodies in the general population is about 2% and reaches 10% for neurological disorders other than TSP. Since our initial report, the association between spastic paraparesis and HTLV‐I has been confirmed in Jamaica, Colombia, and Japan, suggesting the neurotropism of this lymphotropic human retrovirus.
A correlation between cerebrospinal fluid mylein basic protein and anti–myelin basic protein in multiple sclerosis patients
Authors: Warren Kenneth G. , Catz Ingrid
Published: January 2005

Free and bound levels of myelin basic protein (MBP) and anti–myelin basic protein (anti‐MBP) antibodies were measured by radioimmunoassay in the cerebrospinal fluid of patients with multiple sclerosis who were experiencing acute exacerbations or progressing disease. In a cross‐sectional study, free levels of MBP correlated with those of free anti‐MBP, and bound MBP levels correlated with those of bound anti‐MBP in both groups of patients with active disease. However, acute exacerbations of multiple sclerosis were characterized by higher free MBP and anti‐MBP levels with lower levels of bound fractions. Conversely, patients with progressing disease had higher titers of bound than free fractions. Longitudinal studies of individual patients confirmed the association of higher titers of free anti‐MBP with acute exacerbations and higher levels of bound anti‐MBP with chronic progressing disease.
Adrenoleukodystrophy: Dietary oleic acid lowers hexacosanoate levels
Authors: Rizzo William B. , Phillips Mary W. , Dammann Andrea L. , Leshner Robert T. , Jennings Sandra S. , Avigan Joel , Proud Virginia K.
Published: January 2005

Adrenoleukodystrophy (ALD) is an X‐linked disorder characterized by demyelination, adrenal insufficiency, and accumulation of saturated very‐long‐chain fatty acids (VLFA), particularly hexacosanoate (C26:0). We treated 5 patients with adrenoleukodystrophy (3 males and 2 symptomatic female carriers) for 6 months with a diet enriched in oleic acid (C18:1) and moderately restricted in C26:0. Elevated plasma and erythrocyte levels of C26:0 decreased in a time‐dependent manner during treatment. Total plasma C26:0 concentration was lowered by 50 9% ± (p < 0.01); it became normal in the female carriers. The total erythrocyte level of C26:0 decreased (44 ± 5%; p < 0.001) into the normal range in all patients. Significant decreases were noted in the saturated VLFA composition of plasma and erythrocyte sphingomyelin and erythrocyte phosphatidylcholine during dietary treatment. In general, decreases in saturated VLFA levels were accompanied by increases in monounsaturated VLFA levels, while total VLFA values did not change. This novel approach to the treatment of adrenoleukodystrophy, in which there is an exchange of monounsaturated VLFA for the more toxic saturated VLFA, may prove clinically beneficial in this disorder.
A new dietary therapy for adrenoleukodystrophy: Biochemical and preliminary clinical results in 36 patients
Authors: Moser Ann B. , Borel Janet , Odone Augusto , Naidu Sakkubai , Cornblath David , Sanders Donald B. , Moser Hugo W.
Published: January 2005

A new dietary regimen has been administered for periods ranging from 60 days to 1 1/2 years in 34 patients with various forms of X‐linked adrenoleukodystrophy (ALD), as well as in 1 patient with neonatal ALD and 1 patient with infantile Refsum's disease. The diet combines the administration of a glyceryl trioleate oil (GTO) with the dietary restriction of very‐long‐chain fatty acids (VLFA), particularly hexacosanoic acid (C26:0). Reductions in the levels of plasma C26:0 and other VLFA were achieved in 25 of the 36 patients. Fifteen of these 25 patients were treated for more than 100 days. The mean reduction of the plasma C26:0 level was 53% (range, 22 to 73%) in these 15 patients. While the focus of the study was on biochemical variables, comparison of pre‐ and post‐diet studies of peripheral nerve function showed improvement in 1 patient with adrenomyeloneuropathy (AMN) and 1 heterozygote. In contrast, 2 patients with ALD onset in childhood developed new neurological deficits while on therapy. We conclude that it is possible to lower plasma VLFA levels in ALD patients. A clinical trial is indicated to test whether this approach can alter the neurological progression in patients with AMN or in symptomatic heterozygotes, and to determine whether it can prevent the onset of neurological disability in asymptomatic persons who have the biochemical defect of ALD.
Clinical and magnetic resonance features of primary intracranial arachnoid cysts
Authors: Gandy Samuel E. , Heier Linda A.
Published: January 2005

The clinical features of 33 patients with primary intracranial arachnoid cysts are reviewed. Magnetic resonance imaging was performed in 9 patients and was particularly useful in the multiplanar definition of complex cysts and in differentiating arachnoid cysts from other lesions that are hypodense on computed tomographic scans. Hydrocephalus, cranial nerve palsies, or symptomatic brain compression was considered an indication for surgical intervention in 21 patients. Outcome was uniformly good: mild focal weakness and seizure disorders constituted the sequelae.
False lateralization by surface EEG of seizure onset in patients with temporal lobe epilepsy and gross focal cerebral lesions
Authors: Sammaritano Michele , de Lotbinière Alain , Andermann Frederick , Olivier André , Gloor Pierre , Quesney Luis F.
Published: January 2005

Medically intractable temporal lobe seizures developed in 3 patients with radiological and clinical evidence of a gross focal cerebral lesion acquired early in life. All had bilateral independent epileptogenic discharges from the lateral and inferomesial regions of both hemispheres. Scalp and sphenoidal electroencephalographic (EEG) recordings suggested that the seizures originated from the side contralateral to the known cerebral lesion. Because the lateralizing evidence presented by the ictal EEG conflicted with the clinical data, depth electrodes were implanted stereotaxically to determine the side of onset of the seizures. These studies showed that the seizures originated from the limbic structures of the damaged hemisphere in all 3 patients. At operation the mesial temporal lobe structures showed gliotic changes in all. The patients have remained seizure‐free for 3 to 13 years postoperatively. These findings suggest that depth electrode recordings may be required to clarify the lateralization of seizure onset in such cases. Extracranial EEG findings must be interpreted with caution in epileptic patients who have gross focal lesions.
Examination of motor function in lesions of the spinal cord by stimulation of the motor cortex
Authors: Thompson P. D. , Dick J. P. R. , Asselman P. , Griffin G. B. , Day B. L. , Rothwell J. C. , Sheehy M. P. , Marsden C. D.
Published: January 2005

Electrical stimulation of the motor cortex was performed in 3 patients with cervical cord trauma and in 3 with cervical myelopathy caused by cervical spondylosis. Abnormal conduction in central motor tracts was demonstrated in 5 of the 6 patients; yet in 4 of these, cortical somatosensory evoked potentials from the same limb were of normal latency. In the remaining patient who had normal motor latencies, the somatosensory evoked potentials were delayed on one side. Electrophysiological examination of the motor pathways by cortical stimulation may therefore be of considerable value in the assessment and management of patients with traumatic and compressive disease of the spinal cord.
Expression of human immunodeficiency virus in cerebrospinal fluid of children with progressive encephalopathy
Authors: Epstein Leon G. , Goudsmit Jaap , Paul Deborah A. , Morrison Susan H. , Connor Edward M. , Oleske James M. , Holland Bart
Published: January 2005

The retrovirus that causes acquired immune deficiency syndrome (AIDS) is now designated the human immunodeficiency virus (HIV). The cerebrospinal fluid (CSF) of 27 children with HIV infection was assayed for intra‐blood‐brain barrier (IBBB) synthesis of HIV‐specific antibodies and for the presence of HIV antigen. In this cohort, 11 children had a progressive encephalopathy (PE), 9 had a static encephalopathy (SE), and 7 had normal neurological findings (N). IBBB synthesis of HIV‐specific antibodies was identified (using matched serum and CSF specimens) in 7 of 11 children with PE, 4 of 9 children with SE, and 2 of 7 children with N. HIV antigen was found (using a highly sensitive solid‐phase enzyme immunoassay) in the CSF of 8 of 11 children with PE, none of the children with SE, and none of the 7 children with N. On the basis of these data, we conclude that: (1) IBBB synthesis of HIV antibodies indicates invasion of the central nervous system but may reflect prior or current infection; and (2) HIV antigen in CSF indicates viral expression and correlates with the occurrence of PE. These findings strongly implicate HIV as the causative agent of PE in these children. The assay for HIV antigen in the CSF may be of value in determining the prognosis of children with HIV infection and for evaluating the efficacy of therapeutic agents against this retrovirus.
Catecholamines predict outcome in traumatic brain injury
Authors: Hamill Robert W. , Woolf Paul D. , McDonald Joseph V. , Lee Louyse A. , Kelly Mary
Published: January 2005

Activation of the sympathetic nervous system attends traumatic brain injury, but the association of the severity of neurological impairment and recovery with the extent of sympathetic nervous system stimulation is poorly defined. In this study, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured serially in 33 patients with traumatic brain injury and compared with the Glasgow Coma Score (GSC), which was obtained concurrently. A catecholamine gradient that reflected the extent of brain injury was demonstrated within 48 hours of the injury. In patients with a GCS of 3 to 4, NE and E levels increased four‐ to fivefold and the DA level increased threefold above normal (NE, 1686 ± 416 pg/ml; E, 430 ± 172 pg/ml; DA, 236 ± 110 pg/ml), while patients with mild brain injury (GCS, ≥ 11) had slightly elevated or normal levels. Patients with marked (GCS, 5 to 7) and moderate (GCS, 8 to 10) traumatic brain injuries had intermediate levels. The prognostic value of determining admission levels of NE was shown in patients with an admission GCS of 3 to 4 1 week after injury. Patients with severe and unchanging neurological impairment 1 week after injury had markedly elevated initial NE levels (2,176 ± 531 pg/ml), whereas initial NE levels (544 ± 89 pg/ml) were only mildly elevated in patients who improved to a GCS of greater than 11. These data indicate that markedly elevated NE levels predict outcome in patients with comparable neurological deficits. Thus levels of circulating catecholamines are excellent endogenous and readily quantifiable markers that appear to reflect the extent of brain injury and that may predict the likelihood of recovery.
HIV antigen in the brains of patients with the AIDS dementia complex
Authors: Pumarola‐Sune Tomas , Navia Bradford A. , Price Richard W. , Cordon‐Cardo Carlos , Cho Eun‐Sook
Published: January 2005

Human immunodeficiency virus infection was identified immunohistochemically in the brains of 8 patients with acquired immune deficiency syndrome dementia complex. Using a monoclonal antibody against a structural viral protein (p25), infection was detected in white matter and basal ganglia in a distribution paralleling that of the major neuropathological abnormalities. Viral antigen was identified principally in perivascular and parenchymal macrophages and in multinucleated cells of macrophage origin that were identified morphologically and by immunocytochemical staining for acid phsophatase isozyme. In 4 of the 8 patients, viral antigen was also detected in acid‐phosphatase–negative, process‐bearing neuroglial cells; in 2 patients, antigen was detected in basal ganglion cells that were morphologically consistent with neurons and in alkaline‐phosphatase–positive cells with elongated nuclei that were most likely of endothelial origin.
Familial cavernous malformations of the central nervous system and retina
Authors: Dobyns William B. , Michels Virginia V. , Groover Robert V. , Mokri Bahram , Trautmann James C. , Forbes Glenn S. , Laws Edward R.
Published: January 2005

We studied a family in which 4 persons from three generations had multiple cavernous malformations (“angiomas”) of the central nervous system (CNS) and/or retina and found accounts in the literature of sixteen other families with this condition. In these families with familial cavernous malformation of the CNS and retina, 92% of pathologically documented vascular malformations were cavernous; 50% of those subjects affected had multiple CNS and/or retinal vascular malformations and 68% (excluding probands) were symptomatic. Cutaneous vascular lesions were an inconsistant manifestation. Autosomal dominant inheritance with high penetrance was confirmed.
Peduncular hallucinosis: Magnetic resonance imaging confirmation of mesencephalic infarction during life
Authors: Geller Thomas J. , Bellur Srinath N.
Published: January 2005

We describe a patient with peduncular hallucinosis and a mesencephalic infarct; the infarct was diagnosed during life by magnetic resonance imaging.
Diencephalic seizures: Responsiveness to bromocriptine and morphine
Authors: Bullard Dennis E.
Published: January 2005

Two patients with posttraumatic diencephalic seizures, characterized by autonomic dysfunction and extensor posturing, had partial responses to bromocriptine and complete responses to morphine. Probable synergism between the two agents was noted. These 2 cases suggest the potential effectiveness of this regimen for the treatment of diencephalic seizures, raise questions regarding the role of the dopaminergic and opioid systems in this disease entity, and support the hypothesis that diencephalic seizures represent a release phenomenon in the brain.
Factors that influence the occurrence of response variations in Parkinson's disease
Authors: De Jong G. J. , Meerwaldt J. D. , Schmitz P. I. M.
Published: January 2005

Retrospective study of 129 patients treated with dopamine substitution showed that the occurrence of response variations is related to the duration of therapy and not to the nature of the predominant symptom (tremor or hypokinesia and rigidity) or the age of onset of the disease. A relationship was found between the occurrence of response variations and the severity of the disease when levodopa therapy was started. Patients fared worst who were in Hoehn and Yahr stages I and II when levodopa therapy was begun.
Age‐related shrinkage of cortically projecting cholinergic neurons: A selective effect
Authors: Mesulam M‐Marchsel , Mufson Elliott J. , Rogers Joseph
Published: January 2005

The number and size of basal forebrain neurons that provide the cholinergic innervation for the cerebral cortex, amygdala, and hippocampus were studied in young and aged mice. The results showed that these neurons became substantially smaller with increasing age. This effect was relatively selective, since the immediately adjacent cholinergic neurons in the striatum did not show a change of similar magnitude. The shrinkage of these basal forebrain neurons may account for the decline of cholinergic innervation that occurs with age. In the material that we examined, aging did not influence the number of cholinergic neurons in the basal forebrain, only their size. It seems, therefore, that the age‐related changes in cholinergic function (and their putative behavioral consequences) are not associated with a substantial component of irreversible cell death.
Aminergic systems in Alzheimer's disease and Parkinson's disease
Authors: D'Amato Robert J. , Zweig Richard M. , Whitehouse Peter J. , Wenk Gary L. , Singer Harvey S. , Mayeux Richard , Price Donald L. , Snyder Solomon H.
Published: January 2005

Biochemical markers for serotoninegic and catecholaminergic neurons in frontal and temporal poles were examined post mortem in brains of patients with Alzheimer's disease, Parkinson's disease, and the two combined. Binding of [3H]citalopram to serotoninergic uptake sites and levels of serotonin were Decemberreased by 40 to 50% in brains of persons in each disease category. In contrast, significant reductions of catecholaminergic markers were not detected. In all three disease groups, the choline acetyltransferase activity was reduced by 50 to 60%. Binding sites for adenosine (A1), muscarinic cholinergic, phencyclidine, β‐adrenergic, and calcium antagonist receptors were unchanged. We conclude that substantial damage to serotoninergic neurons occurs in persons with Parkinson's and Alzheimer's diseases.
The concept of coupling blood flow to brain function: Revision required?
Authors: Lou Hans C. , Edvinsson Lars , MacKenzie Eric T.
Published: January 2005

A tight coupling exists between brain function and cerebral perfusion in most situations. The Roy and Sherrington hypothesis has been widely accepted to account for the phenomenon: Increased neuronal metabolic activity will give rise to the accumulation of vasoactive catabolites, which decrease vascular resistance and thereby increase blood flow until normal homeostasis is reestablished. However, the hypothesis does not account for the disproportionate increase in flow that occurs in a number of circumstances. There are additional difficulties in reconciling more recent experimental data with the Roy and Sherrington hypothesis. In this review we direct attention toward the rich perivascular nerve supply to all parts of the cerebral circulation as possibly being an alternative control system allowing for rapid parallel changes in flow and neuronal activity.
Risk factors for ischemic stroke: A prospective study in Rochester, Minnesota
Authors: Davis Patricia H. , Dambrosia James M. , Schoenberg Bruce S. , Schoenberg Devera G. , Pritchard David A. , Lilienfeld Abraham M. , Whisnant Jack P.
Published: January 2005

A cohort of 1,804 residents of Rochester, Minnesota, who were at least 50 years old, free of stroke, and who underwent examination at the Mayo Clinic in 1960, was followed for 13 years. During this period, there were 110 first ischemic strokes and 616 deaths without stroke. The time of onset, if available, or the time of diagnosis of potential risk factors was determined for all patients during the study and was used to construct a proportional hazards model of time to occurrence of stroke with time‐dependent risk factors. The model included 8 risk factors (2 fixed and 6 time dependent). For these, the individual relative risk are: 1.6 for age (per 10 years), 2.0 for males, 4.0 for definite hypertension, 3.9 for transient ischemic attacks, 2.2 for hypertensive heart disease, 2.2 for coronary heart disease, 1.7 for congestive heart failure, and 1.7 for diabetes mellitus. Atrial fibrillation was not a significant risk factor using time dependent multivariate analysis.
Effect of levodopa treatment on contrast sensitivity in Parkinson's disease
Authors: Bulens C. , Meerwaldt J. D. , Van der Wildt G. J. , Van Deursen J. B. P.
Published: January 2005

We studies contrast sensitivity function in 10 parkinsonian patients before and after levodopa treatment. Pretreatment contrast sensitivity function was abnormal in 16 of the 20 eyes. After treatment, only high‐frequency loss was observed in 6 eyes. All other types of deficit disappeared under treatment. These changes of contrast sensitivity function following treatment suggest that dopamine is functional transmitter in the visual pathways.
Molecular pathogenesis of neurotropic viral infections
Authors: Gonzalez‐Scarano F. , Tyler Kenneth L.
Published: January 2005

Classical virologists defined a number of viruses that affect the nervous system and identified tissue tropism, extraneural replication, and viremia as important parameters that determine whether viral infections will affect the central nervous system. Molecular techniques are expanding this knowledge by permitting us to relate specific genes and gene products to two defined phenotypes: neuroinvasion and neurovirulence. Two converging situations make this knowledge particularly useful: (1) the development of antiviral drugs and subunit vaccines, which mandate that pathogenesis be related to specific regions of the viral genome; and (2) the expanding problem of central nervous system infections in immunodeficient states.
Lowered cerebral glucose utilization in amyotrophic lateral sclerosis
Authors: Dalakas Marinos C. , Hatazawa Jun , Brooks Rodney A , Di Chiro Giovanni
Published: January 2005

Regional cerebral metabolic rates for glucose (rCMRGlc) were analyzed in 19 studies of 12 patients with amyotrophic lateral sclerosis (ALS) by positron emission tomography (PET) with {18F}2‐fluoro‐2‐deoxy‐D‐glucose. In the 8 ALS patients with upper motor neuron signs, the mean cortical rCMRGlc was significantly lower than in 11 age‐matched control subjects (p < 0.001). The degree of hypometabolism correlated with the duration of the clinical signs and extended throughout the cortex and basal ganglia, but not to the cerebellum. Of the 4 such patients who had repeat PET scans, 3 demonstrated significant subsequent reduction in the rCMRGlc, corresponding to the worsening of the clinical picture. In contrast, 4 ALS patients with disease confined to lower motor neurons and 3 patients with lower motor neuron disease from old paralytic poliomyelitis had normal or near‐normal rCMRGlc throughout the brain. Because histological evidence shows no generalized neuronal cell loss in the cortex of ALS patients, including in some cases the primary motor regions, the demonstration of severe generalized hypometabolism in structurally normal cortex indicates that some cortical neurons exist in a state of neuronal nonfunction, rather than cell death, and that anatomoclinical correlations may be more complex. The data also indicate that ALS with upper motor neuron involvement extends beyond the corticospinal tracts and differs in cortical function from the ALS confined to lower motor neurons or the other lower motor neuron disorders.
Huntington's disease: Changes in tachykinin content in postmortem brains
Authors: Arai Heii , Emson Piers C , Carrasco Luis H.
Published: January 2005

Substance P, neurokinin A, neuropeptide K, and neurokinin B were measured in both control (neurologically normal) and Huntington's disease brains obtained post mortem. All four peptides were significantly reduced in the substantia nigra of Huntington's disease patients compared with the control group. No differences were observed in frontal or temporal cortex except that neuropeptide K was significantly reduced in the frontal cortex of Huntington's disease cases. Correlation of the cell loss observed in the striatum and the tachykinin depletions detected in the substantia nigra in the Huntington's disease brains showed that the degree of cell loss agreed well with the extent of tachykinin depletion. Results of double‐staining immunocytochemistry were consistent with the coexistence of substance P and neurokinin A in the substantia nigra of control brains and showed a marked depletion of immunoreactivity to both in Huntington's disease brains.
Immunoglobulins of Lambert‐Eaton myasthenic syndrome inhibit rat pituitary hormone release
Authors: Login Ivan S. , Kim Yong I. , Judd Allan M. , Spangelo Bryan L. , MacLeod Robert M.
Published: January 2005

We speculated that IgG from patients with Lambert‐Eaton myasthenic syndrome (LES) would inhibit calciumdependent hormone secretion in rat anterior pituitary (AP) cells. Primary cultures of normal AP cells were continuously exposed to crude IgG from an LES patient or from healthy control subjects, and the incubation media were assayed for prolactin (PRL) or growth hormone (GH). The LES IgG caused a time‐ and concentration‐dependent reduction of PRL and GH release compared with control IgG over 0.5 to 48 hours using concentrations of 0.01 to 4.0 mg/ml. The calcium‐channel activator maitotoxin stimulated 45Ca2+ uptake and PRL release from AP cells under control conditions, and the LES IgG significantly reduced both actions of maitotoxin. Thus LES IgG appears to modulate an AP antigenic site, perhaps representing an integral component of voltage‐gated calcium channels that may share properties with similar presynaptic elements at the neuromuscular junction.
In vivo 31P and in vitro 1H nuclear magnetic resonance study of hypoglycemia during neonatal seizure
Authors: Young Richard S. K. , Cowan Barrett E. , Petroff Ognen A. C. , Novotny Edward , Dunham Susan L. , Briggs Richard W.
Published: January 2005

To examine the hypothesis that hypoglycemia has an adverse effect on brain energy state during seizure, neonatal dogs were subjected to bicuculline‐induced seizure while hyperglycemic, normoglycemic, or hypoglycemic. Cerebral blood flow increased and remained elevated in all animals subjected to seizure, regardless of blood or brain glucose concentration. In vivo 31P nuclear magnetic resonance spectroscopy disclosed a small (10–20%) decrease in adenosine triphosphate levels and a greater (20–40%) decline in phosphocreatine levels in animals experiencing seizure, irrespective of whether they were hyper‐, normo‐, or hypoglycemic. In vitro analysis of brain extracts with 1H nuclear magnetic resonance spectroscopy disclosed a significant elevation of lactate in all seizing animals. There were differences in brain alanine, glycine, and β‐hydroxybutyrate levels between the hyperglycemia‐seizure and hypoglycemia‐seizure groups. Alternate substrates such as lactate, fatty acids, or amino acids may be used when neonatal seizure is complicated by hypoglycemia, thereby preventing further deterioration of brain metabolic state.
Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease
Authors: Kowall Neil W. , Kosik Kenneth S.
Published: January 2005

The microtubule‐associated protein tau, a major antigenic component of paired helical filaments, has been demonstrated in neurofibrillary tangles and in neurites of senile plaques. With optimal fixation and histochemical methods, we show the normal axonal location of tau protein in human cerebral cortex and the striking alterations of tau distribution that affect the cortical neuropil in Alzheimer's disease. Normally, cortical tau‐immunoreactive fiber bundles form a pattern resembling that seen with myelin stains. The prominence of white matter staining suggests that tau may be especially enriched in projection systems. Alzheimer's disease causes massive axonal disruption and the dislocation of tau protein from its usual axonal domain into neuronal cell bodies, dendrites, and presynaptic regions. The normal pattern of axonal staining in cortex is disrupted and white matter staining is reduced. Prominent abnormal tau‐immunoreactive neuropil fibers are densely present even in cortical regions without classical neurofibrillary tangle and senile plaque formation. The striking neuropil abnormalities, revealed by the aberrant localization of tau protein, are likely to contribute to neuronal dysfunction in Alzheimer's disease.
Somatic and autonomic function in progressive autonomic failure and multiple system atrophy
Authors: Cohen Jeffrey , Low Phillip , Fealey Robert , Sheps Sheldon , Jiang Nai‐Siang
Published: January 2005

We studied 62 consecutive patients with progressive autonomic failure (PAF) or multiple system atrophy (MSA) (26 PAF; 36 MSA). Patients were well matched in age (67 vs 66 years), duration (39 vs 36 months), and severity of autonomic failure (median values for PAF and MSA). Peripheral somatic neuropathy occurred in 2 patients with PAF and 7 patients with MSA. Postganglionic sudomotor and vasomotor functions were studied using the quantitative sudomotor axon reflex test and supine plasma norepinephrine. The extent and severity of autonomic failure were assessed by the thermoregulatory sweat test, by heart rate responses to deep breathing and the Valsalva maneuver, and by blood pressure recordings. Severe and widespread anhidrosis was found in both PAF and MSA patients. Postganglionic sudomotor failure occurred at the forearm in 50% each of PAF and MSA patients and at the foot in 69% and 66% of PAF and MSA patients, respectively. However, postganglionic sudomotor function was preserved in some patients with anhidrosis on thermoregulatory sweat test, indicating a preganglionic lesion. Vagal abnormalities were found in 77% and 81% of PAF and MSA patients. Supine plasma free norepinephrine values were significantly reduced in PAF (p < 0.001), but not in MSA, patients. Standing plasma norepinephrine values were reduced in both PAF (p < 0.001) and MSA (p < 0.001) patients. We conclude the following: (1) PAF is characterized by combined postganglionic sudomotor and adrenergic failure. (2) MSA is associated with a similar frequency of postganglionic sudomotor failure, but postganglionic adrenergic denervation was uncommon. (3) Preganglionic neuron is also involved in both disorders, but more severely in MSA. (4) Somatic neuropathy may occur.