bluuebunny/crossref_metadata_2025 huggingface dataset:
Gerstmann‐Sträussler‐Scheinker disease: Immunohistological and experimental studies
Authors: Tateishi June , Kitamoto Tetsuyuki , Hashiguchi Hideyuki , Shii Hirofumi
Published: January 2005

The older brother of the patient from whom the Fukuoka‐l strain was isolated was found to have numerous kuru plaques, the main finding common to both siblings. Other clinicopathological features including spongiform change were absent in the older brother. Immunostaining using anti‐kuru plaque core protein and anti‐β‐protein peptide revealed many kuru plaques and a few senile plaques in the older brother. Experimental transmission of the disease to laboratory animals was successful, using tissues from both siblings, through inoculation of fresh brain homogenates, purified prion protein, and formalin‐fixed brain homogenates. Prion protein fractions from the patient's brain shortened the incubation periods and formalin‐fixed mouse brains did not lengthen the periods. The disease in the two brothers can be classified as Gerstmann‐Sträussler‐Scheinker disease, a familial variant of Creutzfeldt‐Jakob disease. Gerstmann‐Sträussler‐Scheinker disease manifests a variety of clinicopathological features. Immunohistological verification of kuru plaques has major diagnostic value in assessing dementia.
Human immunodeficiency virus—associated myopathy: Analysis of 11 patients
Authors: Simpson David M. , Bender Adam N.
Published: January 2005

Neuromuscular disorders reported in association with human immunodeficiency virus (HIV) infection include several forms of peripheral neuropathy and polymyositis. We report 11 patients with HIV‐associated myopathy. Five patients with acquired immunodeficiency syndrome (AIDS), 2 with AIDS‐related complex, and 4 otherwise asymptomatic HIV‐infected patients developed progressive proximal muscle weakness. Serum creatine phosphokinase levels were elevated and electromyography revealed abnormal spontaneous activity and myopathy in most patients. All 8 muscle biopsy specimens showed fiber necrosis. Four had inflammatory infiltrates, and nemaline rod bodies were prominent in 3. Immunosuppressant therapy in 5 patients resulted in improvement. Attempts at viral localization in 4 muscle biopsy specimens were unsuccessful. These findings suggest a distinct association between HIV infection and myopathy with features atypical for polymyositis.
Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis
Authors: Chofflon Michel , Weiner Howard L. , Morimoto Chikao , Hafler David A.
Published: January 2005

A consistent immunological finding in patients with progressive multiple sclerosis is a loss of functional suppression. We have recently found Decemberreases in suppressor inducer T cells in progressive multiple sclerosis as measured by two‐color immunofluorescence using differentiation Marchkers CD4 and 2H4. In the present study, we examined the relationship between functional suppression and circulating CD4 + 2H4 + T cells using a two‐stage assay. (1) T cells were stimulated for 7 days with irradiated non‐T cells (autologous mixed lymphocyte reaction [AMLR]) and harvested. It has previously been shown that suppressor T cells are generated during the course of the AMLR. (2) The AMLR‐generated suppressor T cells were then incubated with mononuclear cells plus pokeweed mitogen, and immunoglobu‐lin (Ig) synthesis was measured. There was less AMLR‐induced suppression of IgG synthesis in patients with progressive multiple sclerosis as compared with normal subjects and patients with other neurological diseases. More importantly, there were significant correlations between Decemberreases in circulating CD4+2H4+ cells and loss of suppression (p < 0.0001) and between Decemberreases in circulating CD4+2H4+ cells and the AMLR (p = 0.009). Thus, the Decemberreases in functional suppression and the Decemberreases in the AMLR in multiple sclerosis appear tightly linked to CD4+2H4+ cells, and their measurement provides a means to monitor suppressor function phenotypically. Decemberreases in suppressor inducer T cells may in part explain immunoregulatory abnormalities observed in multiple sclerosis.
Cognitive deficits in olivopontocerebellar atrophy: Implications for the cholinergic hypothesis of Alzheimer's dementia
Authors: Kish Stephen J. , El‐Awar Munir , Schut Lawrence , Leach Larry , Oscar‐Berman Marchlene , Freedman Morris
Published: January 2005

A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.
A crossover trial of bromocriptine in the treatment of vascular dementia
Authors: Nadeau Stephen E. , Malloy Paul F. , Andrew Michael E.
Published: January 2005

Seven patients with vascular dementia completed an 8‐month randomized double‐blind crossover trial of bromocriptine in a dosage of up to 30 mg per day. Patients were assessed using a modified UCLA Parkinson Rating Scale of symptoms and signs, and neuropsychological testing including the Wechsler Adult Intelligence Scale‐Revised, Wechsler Memory Scale, modified Thurstone Word Fluency Test, Wisconsin Card Sort, a test of visual vigilance, and a reaction time task. Subjects failed to perform significantly better on any measure while on bromocriptine, and on several measures their performance while on the drug was worse.
Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography
Authors: Rosenthal Guy , Gilman Sid , Koeppe Robert A. , Kluin Karen J. , Markel Dorene S. , Junck Larry , Gebarski Stephen S.
Published: January 2005

We compared the severity of motor dysfunction with local cerebral metabolic rates for glucose (lCMRGlc) and the; degree of tissue atrophy in 30 patients with olivopontocerebellar atrophy (OPCA). We devised a scale to quantitate the degree of ataxia in the neurological examinations. lCMRGlc was measured with18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET). Tissue atrophy was assessed by visual rating of computed tomographic scans. PET studies revealed Marchked hypometabolism in the cerebellar vermis, cerebellar hemispheres, and brainstem of OPCA patients compared with 30 control subjects. A significant correlation was found between severity of motor impairment and lCMRGlc within the cerebellar vermis, both cerebellar hemispheres, and the brainstem. A significant but weaker relationship was noted between the degree of tissue atrophy in these regions and clinical severity. Partial correlation analysis revealed that motor dysfunction in OPCA correlated more strongly with lCMRGlc than with the amount of tissue atrophy. These results suggest that the clinical manifestations of OPCA are more closely related to the metabolic state of the tissue than to the structural changes in the cerebellum.
Paroxysmal unilateral dysosmia: A cured patient
Authors: Kaufman Michael D. , Lassiter Kenneth R. L. , Vittal Shenoy B.
Published: January 2005

A 31‐year‐old woman with an 11‐year history of unilateral paroxysmal olfactory hallucinations was cured by resection of the homolateral olfactory bulb, which was believed to be the site of origin of the noxious smell.
Myopathy with unique ultrastructural feature in marchinesco‐sjögren syndrome
Authors: Sewry C. A. , Voit T. , Dubowitz V.
Published: January 2005

We have investigated 3 children aged 6, 3, and 2 years, from 2 families, with the clinical features of Marchinesco‐Sjögren syndrome. Muscle biopsy specimens from all 3 were abnormal and showed srrall vacuoles and slight variation in fiber size. Electron microscopy revealed vacuolation and membranous whorls and, in particular, a unique dense membranous structure associated with nuclei. These cases emphasize the involvement of muscle in Marchinesco‐Sjögren syndrome and the importance of electron microscopy in differentil diagnosis.
Imaging of human brain lesions with an ω3 site radioligand
Authors: Benavides JesùS , Cornu Philippe , Dennis Trevor , Dubois Alain , Hauw Jean‐Jacques , Mackenzie Eric T. , Sazdovitch Véronique , Scatton Bernard
Published: January 2005

The topography and magnitude of increase in peripheral type benzodiazepine binding sites (ω3 sites) was investigated autoradiographically in the brains of patients with ischemic cerebrovascular disease, with multiple sclerosis, and withj malignant glioma.3H‐PK 11195, a selective ω3 site ligand, was employed. A manyfold increase in ω3 site density was observed in all these disease states; this increase reflects macrophage invasion or glial proliferation or both as demonstrated by neuropathological studies carried out in parallel. There was an excellent spatial correlation between increased ω3 site densities and extent of the lesion histologically. Specifically, an elevated density of ω3 sites was observed in the plaques of demyelination in multiple sclerosis patients, in the periphery of infarcted zones in stroke patients, and throughout tumor in patients with grade IV astrocytomas. As our approach is applicable to both tomographic (in vivo) and autoradiographic investigations, imaging of ω3 sites may be considered for the detection and monitoring of the natural evolution of many disorders of the human central nervous system.
Stretch reflex dynamics in spastic elbow flexor muscles
Authors: Powers R. K. , Campbell D. L. , Rymer W. Z.
Published: January 2005

Previous studies of stretch reflexes in patients with spastic hypertonia have emphasized the dynamic character of stretch reflex output. In contrast, our own studies of stretch reflex dynamics in spastic elbow flexor muscles of 14 hemiparetic human subjects have shown that stretch‐evoked torque displays a relatively weak dependence on stretch velocity, and there is generally no preferential enhancement of dynamic as compared with static reflex output. Moreover, stretch reflex dynamics are broadly similar in voluntarily activated spastic and normal elbow flexor muscles. These findings support our hypothesis that spastic hypertonia results primarily from a decrease in stretch reflex threshold. The strong velocity dependence of stretch‐evoked electromyographic activity in initially inactive spastic muscles could be due to a decrease in reflex threshold with increasing stretch velocity, rather than an abnormal velocity‐dependent increase in stretch reflex responsiveness.
Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis
Authors: Pestronk Alan , Adams Robert N. , Cornblath David , Kuncl Ralph W. , Drachman Daniel B. , Rn Lora Clawson
Published: January 2005

We studied the incidence and clinical correlates of serum antibodies to GM1 and GD1a gangliosides in patients with classical amyotrophic lateral sclerosis (ALS) and other “motor nerve” syndromes. Serum antibodies to GM1 and GD1a gangliosides were measured using enzyme‐linked immunosorbent assays. Our results showed that polyclonal immunoglobulin M (IgM) antibodies to the GM1 or GD1a ganglioside or both were present at serum dilutions of 1:25 to 1:4,000 in 78% (57/73) of patients with ALS. Only 8% of normal controls had similar antibodies. The pattern of serum antibody reactivity correlated with the pattern of clinical involvement in our patients. Selective reactivity to GDla ganglioside was common when upper motor neuron signs were prominent. IgM reactivity to GM1 ganglioside was common in ALS patients with prominent lower motor neuron signs. Most patients with motor neuropathies had serum reactivity to both GM1 and GDla gangliosides. These results provide further evidence of ongoing autoimmune processes in ALS patients. There is a strong relationship between serum antiganglioside antibodies and patterns of clinical involvement in ALS.
Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials
Authors: Diener Hans‐Christoph , Scholz Erich , Dichgans Johannes , Gerber Wolf‐Dieter , Jäck Agnes , Bille Artur , Niederberger Uwe
Published: January 2005

The present study used recordings of visual potentials evoked by pattern reversal (VEPs) to investigate the central effects of three drugs used in migraine prophylaxis: the calcium channel blocker nifedipine, the beta‐1‐selective blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients with common or classical migraine who were treated in a double‐blind randomized study over a period of 7 months, while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series analysis. VEPs were recorded at the beginning of a 2‐month baseline period without treatment, after 4 months of treatment, and at the end of a 3‐month washout period. At baseline, migraine patients had significantly higher VEP amplitudes and longer latencies than did a group of 87 healthy control subjects. Patients were separated by statistical analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP latency remained unchanged. VEP amplitudes returned to the initial values at follow‐up in the nonresponders, but stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability of the visual system in patients with migraine, although their action is not directly related to their reduction of migraine frequency.
Positron tomography demonstrates frontal lobe hypometabolism in progressive supranuclear palsy
Authors: Goffinet A. M. , De Voider A. G. , Gillain C. , Rectem D. , Bol A. , Michel C. , Cogneau M. , Labar D. , Laterre C.
Published: January 2005

A regional analysis of cerebral glucose metabolism was carried out in 9 patients with progressive supranuclear palsy by using positron emission tomography with fluorodeoxyglucose as the tracer. A consistent metabolic map of frontal hypometabolism was found in 7 patients. Brain metabolism was normal in 1 subject and diffusely decreased in another. In the 7 patients with selective hypofrontality, motor and premotor areas were severely hypometabolic, while heteromodal association cortex and paralimbic regions were comparatively less affected. Although this pattern of frontal alterations, probably due to disconnection, appeared consistent with the clinical features of the disease, it proved difficult to correlate the metabolic maps with neuropsychological disturbances.
Hypoxic‐ischemic spinal cord injury following perinatal asphyxia
Authors: Clancy Robert R. , Sladky John T. , Rorke Lucy B.
Published: January 2005

The role of spinal cord injury in the pathogenesis of abnormal motor signs (depressed tone and reflexes) following severe perinatal hypoxia‐ischemia was prospectively evaluated by clinical, electrophysiological, and neuropathological examinations in 18 asphyxiated neonates. All infants had an abnormal mental status (lethargy or coma), and seizures were present in 12. Neuromuscular examinations revealed hypotonia or flaccidity and hyporeflexia or areflexia in all infants. Neuropathological examinations of the cerebrum and spinal cord were conducted in the 12 neonates who expired. Cerebral pathological findings included cortical neuronal necrosis in 10 of 12 and subcortical white matter injury in 5 of 12. All infants with coma or seizures displayed diffuse cortical injury, but no injury conformed to a parasagittal “watershed” distribution. Spinal cord gray matter displayed prominent ischemic necrosis in 5 patients who were typically flaccid and areflexic. Electromyographic examinations of all 6 survivors were abnormal, consistent with recent injury to the lower motor neuron above the level of the dorsal root ganglion. We conclude that ischemic injury to anterior horn cells within spinal cord gray matter is relatively common among hypotonic‐hyporeflexic neonates following severe perinatal hypoxia‐ischemia. Although the acute neurological syndrome of neonatal asphyxia is often overshadowed by prominent cerebral signs such as coma and seizures, the motor abnormalities may be partially attributed to concurrent spinal cord injury.
Altered expression of genes for amyloid and cytoskeletal proteins in alzheimer cortex
Authors: Clark Arthur W. , Krekoski Craig A. , Parhad Irma M. , Liston Dane , Julien Jean‐Pierre , Hoar David I.
Published: January 2005

Recent studies have indicated a normal gene dose for the amyloid precursor protein (APP) in Alzheimer's disease (AD). These findings leave open the possibility that elevated levels of messenger RNA (mRNA) for this protein may contribute to the pathogenesis of AD. Using Northern analysis, we compared the levels of mRNA for the APP and 3 cytoskeletal proteins in parietal cortex of 6 brains having marked AD‐type degeneration with the levels of these mRNAs in 6 control samples. The cytoskeletal mRNAs studied were those for the human neurofilament 68‐kDa subunit (HNFL), for α‐tubulin, and for glial fibrillary acidic protein (GFAP). A ribonuclease (RNase) protection assay was also used to compare AD and control HNFL mRNA levels. The mRNAs for APP, HNFL, and α‐tubulin were diminished in AD cortex. The decrement for APP mRNA was less than that for HNFL or α‐tubulin. The message for GFAP in AD cortex showed no loss. The findings support a general deficit in neuronal mRNAs, including that for APP. They do not exclude the possibility of elevated levels of the message for the APP in small neuronal subsets, in subcortical neurons projecting to cortex, or as a generalized phenomenon in earlier stages of the disease.
Early cerebellar degeneration in twins with infantile neuroaxonal dystrophy
Authors: Barlow John K. , Sims Katherine B. , Kolodny Edwin H.
Published: January 2005

Dizygotic twin girls with typical infantile neuroaxonal dystrophy (INAD) were studied at age 19 months with computed tomography and magnetic resonance imaging (MRI). Both methods showed distinct atrophy confined to the cerebellum and MRI revealed diffuse signal abnormality of the cerebellar parenchyma. This neuroimaging evidence for selective early involvement of the cerebellum is consistent with both the typical presenting symptoms and the gross pathological findings in the disorder. Neuroimaging may aid in differentiation of INAD from other neurodegenerative disorders with onset in late infancy, providing impetus for diagnostic biopsy and early genetic counseling.
Pathogenesis of dyskinesias in parkinson's disease
Authors: Mouradian M. M. , Heuser I. J. E. , Baronti F. , Fabbrini G. , Juncos J. L. , Chase T. N.
Published: January 2005

Abnormal involuntary movements complicate the management of a majority of patients with advanced Parkinson's disease. The ability of levodopa to induce dyskinesias and alleviate parkinsonism has generally been considered a continuous dose‐dependent pharmacological spectrum. In this study, the acute dose‐response profile of intravenously administered levodopa for both inducing dyskinesia and alleviating parkinsonism, and its duration of action on these motor manifestations were evaluated in 52 parkinsonian patients. The minimum dose of levodopa required to produce mild dyskinetic movements was significantly lower in patients with fluctuations in motor response compared with those who had a stable response to standard oral therapy; the minimum dose for antiparkinsonian benefit, however, failed to show significant differences. The rate of disappearance of dyskinetic movements was faster than the rate of reappearance of parkinsonian signs following withdrawal of a steady‐state infusion of levodopa. The dissociation of the pharmacodynamic profile of the two major motor effects of levodopa suggests their mediation through two different central pharmacological mechanisms, perhaps involving the two classes of dopamine receptors or other transmitter systems, and could have important implications for the design of future antiparkinsonian agents.
Spinal cord and peripheral nerve pathology in AIDS: The roles of cytomegalovirus and human immunodeficiency virus
Authors: Grafe Marjorie R. , Wiley Clayton A.
Published: January 2005

We examined spinal cords, nerve roots, or peripheral nerves of 27 patients who died with acquired immunodeficiency syndrome (AIDS) for the presence of cytomegalovirus (CMV) and human immunodeficiency virus (HIV) by immunoperoxidase techniques in paraffin‐embedded tissue. Vacuolar myelopathy was seen in 8 of 26 spinal cords (31%) and microglial nodules were seen in 13 (50%). All of the patients with lateral column vacuolar myelopathy showed severe brain pathology. HIV antigens had been detected in the brains of 15 (55%) of the 27 patients but were detected in only 3 (11%) of 26 spinal cords and were not localized to regions of vacuolar myelopathy. This suggests that the vacuolar myelopathy may be due to a remote or indirect effect of HIV or other infectious agent. CMV antigens were detected in none of the patients who showed vacuolar myelopathy but were detected in 2 of the 13 with microglial nodules. Focal nerve root or peripheral nerve inflammation was seen in 7 patients; 4 had CMV antigens and none had HIV antigens. CMV appears to be an important cause of inflammatory peripheral neuropathy in AIDS patients.
Neuropathological abnormalities in developmental dysphasia
Authors: Cohen Morris , Campbell Rebecca , Yaghmai Farviar
Published: January 2005

The brain of a 7‐year‐old girl with developmental dysphasia who died of complications of infectious mononucleosis was examined grossly and histologically. The neuropathological studies revealed atypical symmetry of the plana temporale and a dysplastic gyrus on the inferior surface of the left frontal cortex along the inferior surface of the sylvian fissure. These anomalies are likely related to midgestation, the period of neuronal migration from the germinal matrix to the cerebral cortex, and are consistent with a neurodevelopmental cause of developmental dysphasia.
Postmortem analysis of adrenal–medulla–to–caudate autograft in a patient with parkinson's disease
Authors: Hurtig Howard , Joyce Jeffrey , Sladek John R. , Trojanowski John Q.
Published: January 2005

A 53‐year‐old physician who had a 10‐year history of progressive idiopathic parkinsonism survived for 4 months after autologous adrenal‐medulla‐to‐right‐caudate autograft but he received little clinical benefit. A small number of chromaffin cells in the graft site survived; they expressed neurofilament proteins and chromogranin A, but scant tyrosine hydroxylase. The striatum on both sides showed almost complete loss of [3H]mazindol binding to dopamine‐uptake sites; the density of dopamine receptors was decreased adjacent to the transplant but increased rostral to the transplant. These results demonstrate that autografted chromaffin cells can survive for 4 months after transplantation and that related changes in dopamine receptors can be quantified.
Atherosclerosis: Current concepts on pathogenesis and interventional therapies
Authors: Yatsu Frank M. , Fisher Marc
Published: January 2005

Atherosclerosis, the primary pathological condition accounting for most stroke syndromes, has been the intense focus of epidemiological, basic, and clinical investigations. Since these studies have direct bearing on the prevention of atherothrombotic brain infarction, this review emphasizes those advances in treatment resulting from their findings. The two most prominent theories on the pathogenesis of atherosclerosis relate to aberrations in lipoprotein metabolism and to enhanced proliferation of smooth muscle cells; likely, the theories are complementary. As a practical guideline for preventive therapy, the importance of using the total cholesterol level is stressed, although finer distinctions must rely on the low‐density and high‐density lipoprotein concentrations and their normalization. Since prevention of stroke may ultimately be its most effective therapy, consideration of cholesterol level, akin to strategies for preventing coronary heart disease, and efforts to avert platelet adhesion or aggregation and coagulation are warranted.
Cerebrospinal fluid content of diazepam binding inhibitor in chronic hepatic encephalopathy
Authors: Rothstein Jeffrey D. , McKhann Guy , Guarneri Patrizia , Barbaccia Maria Luisa , Guidotti Alessandro , Costa Erminio
Published: January 2005

The neuropeptide diazepam binding inhibitor (DBI) is an endogeneous allosteric modulator of gamma‐aminobutyric acid (GABA) receptors at the benzodiazepine recognition site. Recent theories on the neurochemical cause for hepatic encephalopathy have implicated activation of inhibitory neurotransmitter GABA systems. In 20 patients with hepatic disease, blood and cerebrospinal fluid (CSF) levels of ammonia and amino acids were measured. As in previous studies there was a selective elevation of CSF amino acids as well as a correlation between CSF glutamine levels and encephalopathy. CSF DBI levels were maximally elevated 5‐fold in patients with hepatic encephalopathy, but they were normal in those patients with liver disease not associated with changes in mental status and in patients with nonhepatic encephalopathy. Levels of DBI correlated with the clinical staging of hepatic encephalopathy. These data suggest that DBI may participate in the modulation of cerebral function in hepatic encephalopathy.
Residual ethylene oxide in hollow fiber hemodialysis units is neurotoxic in vitro
Authors: Windebank Anthony J. , Blexrud Marceil D.
Published: January 2005

Ethylene oxide gas is used to sterilize plastic medical equipment including capillary flow dialysis membranes. To test whether ethylene oxide ratained in the dialyzers might be neurotoxic, tissue culture medium was incubated in the blood compartment of dialyzers. Embryonic rat dorsal root ganglion neurons were then incubated in this medium for up to 5 days. During the first 24 hours axonal growth was normal. During the next 24‐hour period varicosities appeared on axons, and after 4 days neuron cell bodies died. The pattern of degeneration was identical to that observed when cultures were exposed to an atmosphere containing 1 ppm ethylene oxide gas. Culture medium introduced into dialyzers after routine prerinsing still caused degeneration, which was not completely abolished even by a 10‐liter rinse. When medium was exposed to identical dialyzers sterilized by gamma irradiation, no changes were seen in culture. Identical morphological changes were produced by using dialysis patient serum in the culture medium in place of the usual calf bovine serum. Such changes were never seen with control human serum. Since ethylene oxide is toxic to the human peripheral nervous system, it is proposed that ethylene oxide in dialyzers may contribute to the progressive neuropathy observed in patients on long‐term hemodialysis.
Evidence for a novel picornavirus in human dermatomyositis
Authors: Rosenberg Neil L. , Rotbart Harley A. , Abzug Mark J. , Ringel Steven P. , Levin Myron J.
Published: January 2005

We prepared RNA probes from cloned segments of human and murine enteroviruses (EVs) for in situ hybridization of skeletal muscle biopsies from patients with dermatomyositis (DM), polymyositis, other inflammatory myopathies, and noninflammatory muscle diseases, and from normal control subjects. A probe derived form Theiler's murine encephalomyelitis virus (TMEV) detected viral RNA within mononuclear cells of the interstitial connective tissue in 3 of 5 patients with adult‐onset DM. None of these patients showed positive hybridization to probes derived from human EVs (poliovirus type 1 and Coxsackei virus B3) applied to subjacent sections of the same biopsies. The remaining 2 adult DM patients, 4 patients with childhood‐onset DM, and 24 and non‐DM patients did not react with either TMEV or human entervirus probes. Histochemical stains for esterase and immunoperoxidase stains for Mac‐1 antigen in the 3 DM patients who reacted positively revelaed positive cells in the same distribution as, but in far greater number than, those positive by in situ hybridization. Immunoperoxides staining for HLA‐DR antigens revealed positive cells in the same distribution and number as were seen with the TMEV probe. We conclude that an EV‐like agent, more closely related to TMEV than to human EVs, may be associated with DM and that this agent is probably localized within muscle macrophages that express class II major histocompatibility complex antigens.
Abnormal pattern electroretinogram in Alzheimer's disease: Evidence for retinal ganglion cell degeneration?
Authors: Katz Barrett , Rimmer Steve , Iragui Vicente , Katzman Robert
Published: January 2005

We recorded pattern‐reversal electroretinograms, flash electroretinograms, pattern‐reversal visual evoked potentials, and flash visual evoked potentials in 6 patients with clinically diagnosed Alzheimer's disease and 6 age and sex matched control subjects. The mean amplitude of the pattern‐reversal electroretinogram in the Alzheimer patients was significantly less than that of the control group (p = 0.004). This anomaly of the pattern‐reversal electroretinogram may be a reflection of documented axonal depletion within the optic nerve and the degeneration of retinal ganglion cells seen in Alzheimer's disease. We found Alzheimer patients to have normal pattern‐reversal visual evoked potentials and flash electroretinograms, but a delayed second positive component of the flash visual evoked potential. This combination of findings may be of diagnostic import in Alzheimers disease.
Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration
Authors: de Volder A. G. , Francart J. , Laterre C. , Dooms G. , Bol A. , Michel C. , Goffinet A. M.
Published: January 2005

Nine positron emission tomography studies of regional cerebral glucose metabolism were performed in 7 patients with probable striatonigral degeneration, a disorder characterized by parkinsonian features and absent or poor response to L‐dopa. When compared with values obtained in normal volunteers, mean cerebral glucose metabolism was slightly reduced in subjects with striatonigral degeneration who, in addition, had a marked (20.5%, ± 3 SD) relative hypometabolism in putaminal and caudate nuclei. Significant hypometabolism was also found in motor/premotor as well as in prefrontal cortex. In 2 subjects who were studied twice a deterioration of relative striatal metabolism paralleled clinical evolution. Magnetic resonance imaging disclosed the presence of abnormal iron deposits in the putamen in all cases but showed no cortical anomalies. These results suggest that positron emission tomography with [18F] fluorodeoxyglucose may provide an index of cell and processes degeneration in the striatum in striatonigral degeneration and is able to detect functional deficits in frontal cortex. The presence of striatal hypometabolism might be a predictor of a poor reponse to L‐dopa.
Antiphospholipid antibodies
Authors: Levine Steven R. , Welch K. M. A.
Published: January 2005

Lupus anticoagulants and anticardiolipin antibodies, known collectively as antiphospholipid antibodies, are becoming established as markers for increased risk of thrombosis, including ischemic cerebrovascular disease. In this brief review, we highlight evidence for an against a pathogenetic role of these antibodies in ischemic brain disease and comment on currently available laboratory studies to detect them. Future research on the association of antiphopholipid antibodies with nerological disease should focus on establishing the pathogenicity of these antibodies, identifying groups at high risk for recurrent ischemic cerebrovascular events, and initiating prospective multicenter natural history and treatment protocols.
Patterns of plasma levels of catechols in neurogenic orthostatic hypotension
Authors: Goldstein David S. , Polinsky Ronald J. , Garty Moshe , Robertson David , Brown Robert T. , Biaggioni Italo , Stull Robin , Kopin Irwin J.
Published: January 2005

Patients with neurogenic orthostatic hypotension can have deficits in sympathetic neural function at any of several levels of the sympathetic neuraxis. We determined whether patterns of plasma levels of dopa, norepinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid would distinguish patients with orthostatic hypotension associated with multiple system atrophy, pure autonomic failure, or deficiency of dopamine‐β‐hydroxylase. Plasma levels of catechols were normal in most patients with multiple system atrophy, consistent with relatively intact peripheral sympathetic neurons; in contrast, most patients with pure autonomic failure had decreased levels of all four catechols, consistent with degenerative loss of sympathetic nerve endings. Patients with deficiency of dopamine‐β‐hydroxylase had increased levels of dopa and dihydroxyphenylacetic acid and markedly decreased levels of norepinephrine and dihydroxyphenylglycol, suggesting compensatory increases in sympathetic nerve activity in the absence of norepinephrine biosynthesis. Subgroups of patients with pure autonomic failure or multiple system atrophy had low levels of norepinephrine with normal levels of dopa, dihydroxyphenylglycol, and dihydroxyphenylacetic acid, consistent with normal catecholamine biosynthesis and decreased postganglionic sympathetic nerve traffic or decreased exocytotic release from sympathetic nerve endings. The results demonstrate the value of examining patterns of plasma levels of catechols to elucidate mechanisms of neurogenic orthostatic hypotension.
Peripheral neuropathy in amyotrophic chorea‐acanthocytosis
Authors: Vita G. , Serra S. , Dattola R. , Santoro M. , Toscano A. , Venuto C. , Carrozza G. , Baradello A.
Published: January 2005

We investigated involvement of the peripheral nervous system in 6 patients with amyotrophic chorea‐acanthocytosis. Electromyographic and neurographic findings, and pathological changes as demonstrated by examination of biopsy specimens of muscle and sural nerve indicate that most patients had an axonal sensorimotor polyneuropathy with more pronounced involvement of the distal portion of the nerves. Results obtained in one patient raised the question of an anterior horn cell disorder.
Neurological and neuropshychological manifestations of HIV‐1 infection: Association with AIDS‐related complex but not asymptomatic HIV‐1 infection
Authors: Janssen Robert S. , Saykin Andrew J. , Cannon Lyn , Campbell John , Pinsky Paul F. , Hessol Nancy A. , O'Malley Paul M. , Lifson Alan R. , Doll Lynda S. , Rutherford George W. , Kaplan Jonathan E.
Published: January 2005

To determine whether neurological and neuropsychological abnormalities are associated with clinical manifestations of human immunodeficiency virus type 1 (HIV‐1) infection in men who do not have acquired immunodeficiency syndrome (AIDS), we performed a historical prospective and cross‐sectional study. One hundred HIV‐1 seropositive homosexual or bisexual men, of whom 26 had AIDS‐related complex, 31 had generalized lymphadenopathy, and 43 had no signs or symptoms of HIV‐1 infection, and 157 HIV‐1 seronegative men were enrolled from a cohort of 6,701 men who were originally recruited between 1978 and 1980 for studies of hepatitis B virus infection. Evaluation included medical history, physical examination, and neuropsychological tests. Of 26 HIV‐1 seropositive subjects with AIDS‐related complex, 11 (42%) reported neurological, cognitive, or affective symptoms compared with 30 (19%) of 157 HIV‐1 seronegative subjects (relative risk ≈ 2.2, p = 0.02). On neuropsychological testing, subjects with AIDS‐related complex performed at a significantly lower level than the HIV‐1 seronegative group (p = 0.001). A significantly higher percentage of subjects with AIDS‐related complex (8[31%] of 26) than HIV‐1 seronegative subjects (19 [12%] of 157) had abnormal results on two or more neuropsychological tests (rate ratio = 2.5, p = 0.03). symptoms and impairment on neuropsychological tests were correlated only within the group who had AIDS‐related complex. Subjects with generalized lymphadenopathy and subjects who had no signs or symptoms of HIV‐1 infection were not different from HIV‐1 seronegative subjects with respect to symptoms or performance on neuropsychological tests. Absolute T‐helper lymphocyte count and estimated duration of HIV‐1 infection were not associated with neuropsychological test results. These findings suggest that neurological and neuropsychological abnormalities are associated with AIDS‐related complex but not with asymptomatic HIV‐1 infection.
Neuropathological changes in early HIV‐1 dementia
Authors: McArthur Justin C. , Becker P. Scott , Parisi Joseph E. , Trapp Bruce , Selnes Ola A. , Cornblath David R. , Balakrishnan Janaki , Griffin John W. , Price Donald
Published: January 2005

Early pathological abnormalities in human immunodeficiency virus (HIV‐1)–related dementia have not been well documented. We report a homosexual man with fatigue and intermittent diarrhea in whom early HIV‐1–related dementia was demonstrated during neurological screening in the Multicenter AIDS Cohort Study. Within 4 months he died of massive epistaxis, and the brain revealed astrocytosis of white matter and mild pallor of myelin staining in the absence of inflammation, multinucleated giant cells, and brain atrophy.
Divisional oculomotor nerve paresis caused by intrinsic brainstem disease
Authors: Ksiazek Susan M. , Repka Michael X. , Maguire Albert , Harbour Robert C. , Savino Peter J. , Miller Neil R. , Sergott Robert C. , Bosley Thomas M.
Published: January 2005

Two patients with findings ascribable to superior branch oculomotor nerve paresis and one patient with findings ascribable to an inferior branch paresis are described. In each patient the paresis was caused by an intra‐axial midbrain lesion. These patients represent the first described cases of divisional oculomotor nerve paresis caused by intrinsic brainstem disease.
Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue
Authors: Aberer E. , Brunner C. , Suchanek G. , Klade H. , Barbour A. , Stanek G. , Lassmann H.
Published: January 2005

The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.
Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: A prospective magnetic resonance imaging study
Authors: Brunner John E. , Redmond Janice M. , Haggar Allan M. , Kruger Davida F. , Elias Stanton B.
Published: January 2005

The rate at which profound hyponatremia should be corrected is the focus of a recent clinical debate. We prospectively studied neurological outcomes with serial magnetic resonanace imaging in 13 hyponatremic subjects with serum sodium concentrations of less than 115 mmol/L (mean initial serum sodium concentration, 103.7; range, 93–113 mmol/L). All subjects were corrected to mildly hyponatremic levels at 24 hours and ultimately underwent an increase in serum sodium concentration of 25 mmol/L without development of hypernatremia. Magnetic resonance imaging revealed the development of pontine lesions in 3 patients. The correction rate of hyponatremia over the first 24 hours was significantly faster in patients with pontine lesions (mean ± SD, 1.25 ± 0.4 mmol/(L ± hr) versus 0.74 ± 0.3 mmol/(L ± hr); ±<0.05). Initial sodium concentration was also significantly lower in the pontine lesion group (97.3 ± 6.7 vs 105.6 ± 5.2 mmol/L,p ± <0.05). We conclude that the correction rate of hyponatremia plays a significant role in the pathogenesis of pontine lesions in individuals with profound hyponatremia who undergo large increases in sodium concentration as a result of severe initial hyponatremia.
Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage
Authors: Hasan Djo , Wijdicks Eelco F. M. , Vermeulen Marinus
Published: January 2005

The association between hyponatremia and cerebral ischemia was investigated in a consecutive series of 208 patients with subarachnoid hemorrhage who had a daily fluid intake of at least 3 L and in whom fluid restriction, to correct hyponatremia, was not applied. Hyponatremia occurred in 70 (34%) of the 208 patients. The occurrence of cerebral ischemia in patients with hyponatremia, 17 (24%) of 70 patients, was significantly higher than in patients without hyponatremia, 17 (12%) of 138 patients (χ2 = 4.028, p = 0.045). Cerebral ischemia was not more often fatal in hyponatremic patients than in patients without hyponatremia. We conclude that patients with hyponatremia are at increased risk of developing cerebral ischemia even if fluid restriction is not applied.
The diagnosis and treatment of cerebral mycotic aneurysms
Authors: Brust John C. M. , Dickinson P. C. Taylor , Hughes James E. O. , Holtzman Robert N. N.
Published: January 2005

Seventeen patients were treated for 28 documented cerebral mycotic aneurysms. Initial neurological symptoms were attributable to aneurysm rupture in only 7 patients, and in 3 of them symptoms did not suggest subarachnoid hemorrhage. Six patients presented with embolic infarction and 1 with meningitis; in 3 patients it was uncertain if aneurysm rupture occurred. Four patients had rupture of at least one aneurysm while receiving appropriate antibiotic treatment and another had rupture at the conclusion of therapy. Of 20 aneurysms followed angiographically or with computed tomography during medical treatment, 10 became smaller or disappeared and 10 remained unchanged or enlarged, 1 with fatal rupture. Eight ruptured aneurysms were surgically excised; 2 of the patients with ruptured aneurysms died and 2 had residual aphasia or cognitive impairment. All 4 patients whose only surgery was for an unruptured aneurysm made uneventful recoveries. Recognizing the retrospective and anecdotal nature of our data and the differing views of previous investigators, we recommend: (1) that careful neurological examination, computed tomography, and (unless contraindicated) lumbar puncture be performed on any patient with endocarditis; (2) that those with neurological abnormalities not attributable to systemic toxicity, including pleocytosis in the cerebrospinal fluid or apparent infarction on computed tomographic scans, undergo four‐vessel cerebral angiography; (3) that single accessible mycotic aneurysms in medically stable patients be promptly excised, with individualization of multiple or proximal aneurysms; and (4) that repeat angiography be performed at the conclusion of antibiotic therapy in patients requiring long‐term anticoagulation. Our data do not allow us to predict whether performing repeat angiography on all neurologically abnormal patients or initial angiography on all endocarditis patients would do more harm than good.
Mitogen accumulation in von Recklinghausen neurofibromatosis
Authors: Ratner Nancy , Lieberman Michael A. , Riccardi Vincent M. , Hong Dingming
Published: January 2005

Most, but not all, patients with von Recklinghausen neurofibromatosis develop tumors (neurofibromas) that contain large numbers of Schwann cells and fibroblasts. To begin to understand the molecular events that contribute to cell proliferation in these benign tumors, we have analyzed extracts of neurofibromas to determine whether they contain mitogens for Schwann cells or fibroblasts, or both. Schwann cell and fibroblast mitogens are present in neurofibroma extracts. All the neurofibromas analyzed contain a Schwann cell mitogen similar to a neuronal cell surface molecule known to stimulate Schwann cell proliferation during normal development; this mitogen also stimulates fibroblast proliferation. Basic fibroblast growth factor is present in 60% of tumors evaluated. Accumulation of mitogenic substances may contribute to the growth of neurofibromas.
A long‐term prospective study of optic neuritis: Evaluation of risk factors
Authors: Sandberg‐Wollheim Magnhild , Bynke Hans , Cronqvist Sten , Holtås Stig , Platz Per , Ryder Lars P.
Published: January 2005

Eighty‐six patients with monosymptomatic optic neuritis of unknown cause were followed prospectively for a median period of 12.9 years. At onset, cerebrospinal fluid (CSF) pleocytosis was present in 46 patients (53%) but oligoclonal immunoglobulin in only 40 (47%) of the patients. The human leukocyte antigen (HLA)‐DR2 was present in 45 (52%). Clinically definite multiple sclerosis (MS) was established in 33 patients. Actuarial analysis showed that the cumulative probability of developing MS within 15 years was 45%. Three risk factors were identified: low age and abnormal CSF at onset, and early recurrence of optic neuritis. Female gender, onset in the winter season, and the presence of HLA‐DR2 antigen increased the risk for MS, but not significantly. Magnetic resonance imaging detected bilateral discrete white matter lesions, similar to those in MS, in 11 of 25 patients, 7 to 18 years after the isolated attack of optic neuritis. Nine were among the 13 with abnormal CSF and only 2 belonged to the group of 12 with normal CSF (p = 0.01). Normal CSF at the onset of optic neuritis conferred better prognosis but did not preclude the development of MS.
Immunocytochemical and ultrastructural studies of Pick's disease
Authors: Murayama Shigeo , Mori Hiroshi , Ihara Yasuo , Tomonaga Masanori
Published: January 2005

Cerebral cortical changes in 10 cases with Pick's disease were studied immunocytochemically and ultrastructurally. All cases contained Pick's argentophilic bodies and ballooned neurons. The antibodies against phosphorylated tau proteins that intensely stained all Pick bodies recognized numerous neuronal processes around Pick body–bearing cells and focal portions in the perikarya of ballooned neurons. Monoclonal and polyclonal anti‐ubiquitin antibodies stained not only some Pick bodies with variable intensity, but also the perikarya of all ballooned neurons. Ultrastructurally, Pick bodies consisted of accumulation of randomly oriented, approximately 15‐nm straight filaments and paired twisted profiles with a minimal diameter of 13 nm, maximal diameter of 26 nm, and twist periodicity of 120 nm. These Pick body–type filaments were also observed in the perikarya of ballooned neurons and neuronal processes around Pick body–bearing cells. Our studies demonstrate, for the first time, the characteristic pathological feature of neuropil in Pick's disease. Pick body–bearing cells and ballooned neurons show unique immunocytochemical and ultrastructural properties that may be a clue to the pathogenesis of Pick's disease.