bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral somatosensory evoked potentials in four patients with long‐standing surgical hemispherectomy
Authors: Mauguière François , Desmedt John E.
Published: January 2005

Four patients were studied electrophysiologically 8 to 24 years after surgical removal of one cerebral hemisphere without damage to the striatum or diencephalon. Somatosensory evoked potentials(SEPs)to electrical stimulation of the median nerve on the left or right side were averaged and mapped out over the scalp. Stimulation on the side opposite to the missing hemisphere evoked brief P9 and P14 farfields and a slow N18 negative potential of 15‐to 25‐msec duration bilaterally. No additional focal response was detected over the remaining (ipsilateral) hemisphere for 60 msec after the stimulus. Because long‐standing hemispherectomy entails massive retrograde degeneration of thalamocortical neurons, the preserved P14 and N18 responses must reflect neural activities generated below the thalamus that are volume conducted to the scalp bilaterally. The data clarify several current issues in the evaluation of SEP components.
Complex partial status epilepticus provoked by “crack” cocaine
Authors: Ogunyemi Abayomi O. , Locke George E. , Kramer Lynn D. , Nelson Lowell
Published: January 2005

A 53‐year‐old woman with a history of chronic abuse of “crack” cocaine developed isolated complex partial status epilepticus after 3 days of frequent cocaine use. The electroencephalogram demonstrated focal epileptiform activity. Follow‐up for 1 year during which she reported continuous abstinence from cocaine and anticonvulsants revealed no recurrence of seizures.
Alteration in extracellular amino acids after traumatic spinal cord injury
Authors: Panter S. Scott , Yum Sabrina W. , Faden Alan I.
Published: January 2005

It has recently been demonstrated that N‐methyl‐D‐aspartate antagonists limit tissue damage after spinal cord trauma, implicating excitatory amino acids in the secondary injury response. To determine whether spinal cord trauma alters the concentrations of extracellular amino acids, microdialysis was conducted in spinal cord during and after administration of impact trauma. Extracellular concentrations of excitatory, inhibitory, and nontransmitter amino acids were elevated after trauma, with the degree of increase related to severity of injury. Moderate trauma resulted in an immediate but transient increase (200‐400%) in the extracellular levels of all amino acids measured. Severe trauma produced a more prolonged and significant increase (400‐630%) in the concentrations of extracellular amino acids, including aspartate and glutamate. These results are consistent with the hypothesis that excitatory amino acids may contribute to delayed tissue injury after central nervous system trauma.
Neuronal intranuclear inclusion disease in a child: Diagnosis by rectal biopsy
Authors: Goutières F. , Mikol J. , Aicardi J.
Published: January 2005

A 15‐year‐old boy presented with progressive pyramidal and extrapyramidal signs, anterior horn cell dysfunction, and behavioral disturbances suggesting a diagnosis of neuronal intranuclear inclusion disease. The diagnosis was confirmed by examination of a rectal biopsy specimen that showed typical intranuclear inclusions in the neurons of the myenteric plexus. Diagnosis of neuronal intranuclear inclusion disease during life appears to be possible.
Prenatal and perinatal antecedents of febrile seizures
Authors: Nelson Karin B. , Ellenberg Jonas H.
Published: January 2005

We examined prenatal and perinatal characteristics as possible risk factors for febrile seizures in a large pediatric population. Family history was among the few identified factors that made an important contribution to vulnerablility to febrile seizures; however, no more than 6% of febrile seizures could be attributed to a characteristic of family history. Maternal illness, smoking history, and a few rare neonatal characteristics were associated with increases in risk. No complication of labor or delivery was an important risk factor for febrile seizures.
A survey of epileptic disorders in Southwest France: Seizures in elderly patients
Authors: Loiseau Jérǒme , Loiseau Pierre , Duché Bernard , Guyot Martine , Dartigues Jean‐François , Aublet Bruno
Published: January 2005

An underestimation of epileptic seizures occurring in aged patients is likely. In an epidemiological survey undertaken in Southwest France, the annual incidence rate per 100,000 persons 60 years or older was 127.2 for all seizures (101.3 in persons aged 60 to 69, 150.4 in those aged 70 to 79, and 139.9 in persons 80 years or older). It was 34.1 for symptomatic localization‐related and undetermined epilepsies, 16.1 for isolated seizures, and 77.0 for seizures related to an acute situation, such as metabolic derangements, stroke, or head trauma. In this survey, seizures with an onset age of 60 or older represented 28.0% of the confirmed epilepsies, 17.5% of the isolated seizures, and 52.6% of the acute symptomatic seizures. These figures differ dramatically from those in most previous reports concluding that age‐specific incidence declined through adult life. They are closer to the data from more recent reports. The main reason for such a high incidence of epileptic seizures in elderly patients is the number of acute symptomatic (or situation‐related) seizures. However, even chronic epilepsies increase in frequency in aging persons. Cerebrovascular disease was the most frequently recognized origin (53.9% of the patients with confirmed epilepsies) and brain tumor was found in 32.9% of the patients.
Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease
Authors: Halliday G. M. , Li Y. W. , Blumbergs P. C. , Joh T. H. , Cotton R. G. H. , Howe P. R. C. , Blessing W. W. , Geffen L. B.
Published: January 2005

Regional loss of immunohistochemically identified neurons in serial sections through the brainstem of 4 patients with idiopathic Parkinson's disease was compared with equivalent sections from 4 age‐matched control subjects. In the Parkinson brains, the catecholamine cell groups of the midbrain, pons, and medulla showed variable neuropathological changes. All dopaminergic nuclei were variably affected, but were most severely affected in the caudal, central substantia nigra. The pontine noradrenergic locus ceruleus showed variable degrees of degeneration. There was also a substantial loss of substance P–containing neurons in the pedunculopontine tegmental nucleus. However, the most severely affected cell group in the pons was the serotonin‐synthesizing neurons in the median raphe. In the medulla, substantial neuronal loss was found in several diverse cell groups including the adrenaline‐synthesizing and neuropeptide Y–containing neurons in the rostral ventrolateral medulla, the serotonin‐synthesizing neurons in the raphe obscurus nucleus, the substance P–containing neurons in the lateral reticular formation, as well as the substance P–containing neurons in the dorsal motor vagal nucleus. Lewy bodies were present in immunohistochemically identified neurons in many of these regions, indicating that they were affected directly by the disease process. These widespread but region‐ and transmitter‐specific changes help account for the diversity of motor, cognitive, and autonomic manifestations of Parkinson''s disease.
Long latency event‐related potentials in patients infected with human immunodeficiency virus
Authors: Goodin Duoglas S. , Aminoff Michael J. , Chernoff David N. , Hollander Harry
Published: January 2005

Long latency auditory evoked potentials were recorded in 55 homosexual men infected with human immunodeficiency virus (HIV). Forty‐one of these patients were asymptomatic from the infection and 14 had clinical signs of illness. Nine of the symptomatic patients were demented and 8 (6 of whom were demented) met other diagnostic criteria for acquired immunodeficiency syndrome (AIDS). Cerebral responses were recorded from Fz, Cz, and Pz electrode placements referred to linked mastoids and averaged separately to rare (2,000 Hz) and frequent (1,000 Hz) tones presented in a pseudorandom sequence. Electroencephalography (EEG) was performed in 54 of the patients and magnetic resonance imaging (MRI) or computed tomography (CT) was done in 14 (13 of whom were symptomatic from the infection). The latency of N1, P2, N2, and P3 components was delayed in HIV‐positive patients compared to normal and this was particularly so for the N1, N2, and P3 components. These changes were more marked in those patients who were symptomatic from their infection, especially in those who were demented. They were, however, present to a lesser degree even in asymptomatic (Class II) patients. Thus, 78% of the demented patients and 28% of nondemented patients had a delay in latency of at least one of the evoked potential components beyond the upper limit of our normal population. By contrast, the EEG was normal in all patients with asymptomatic HIV infection and most symptomatic patients, although 5 patients in this latter group had mild generalized slowing. MRI and CT findings were similarly nonspecific, particularly in the nondemented group. Our findings suggest that long latency auditory evoked potentials may be particularly useful in the evaluation of HIV‐infected patients, possibly permitting the early recognition of HIV encephalopathy and identifying those patients with a worse prognosis or in need of more aggressive management; perhaps, also, recording these potentials will permit the course of this disorder, and its response to therapy, to be followed.
Preliminary trial of 3,4‐diaminopyridine in patients with multiple sclerosis
Authors: Bever Christopher T. , Leslie James , Camenga David L. , Panitch Hillel S. , Johnson Kenneth P.
Published: January 2005

Ten patients with multiple sclerosis (MS) were enrolled in a preliminary trial of the potassium channel blocker, 3,4‐diaminopyridine, to evaluate drug toxicity and pharmacokinetics. The patients were treated with oral 3,4‐diaminopyridine, first with increasing single doses up to 100 mg and then with divided dosage for up to 3 weeks. Paresthesias were reported by all patients and abdominal pain was dose limiting in 6 patients. 3,4‐Diaminopyridine levels and half‐life varied widely from patient to patient. Cerebrospinal fluid levels of 3,4‐diaminopyridine were about 10% of those in serum. Neither seizures nor epileptiform changes on electroencephalographic examination occurred. Small reversible improvements in specific neurological deficits were seen on examination in all patients and reversible improvement in visual evoked response latencies were found in 2 patients. These results suggest that further study of 3,4‐diaminopyridine in patients with MS is warranted.
The dysarthria—clumsy hand syndrome: A distinct clinical entity related to pontine infarction
Authors: Glass Jonathan D. , Levey Allan I. , Rothstein Jeffrey D.
Published: January 2005

Using magnetic resonance imaging, we studied 6 patients with the dysarthria–clumsy hand syndrome. All were found to have pontine infarctions contralateral to the symptomatic side. Clinically, these patients exhibited dysarthria; “clumsiness,” characterized by dysmetria, dysrhythmia, dysdiadochokinesia and sometimes truncal and gait ataxia; and mild ipsilateral weakness. Previous clinical‐anatomical correlations for this syndrome are limited by inconsistencies in clinical diagnostic criteria and low‐resolution imaging methods. In our patients, and in a review of the literature, the overwhelming majority of patients with the dysarthria–clumsy hand syndrome had pontine infarcts. We conclude that if rigid clinical criteria are used, the label of the dysarthria–clumsy hand syndrome predicts a lesion in the contralateral basis pontis.
Mania after brain injury: Neuroradiological and metabolic findings
Authors: Starkstein Sergio E. , Mayberg Helen S. , Berthier Marcelo L. , Fedoroff Paul , Price Thomas R. , Dannals Robert F. , Wagner Henry N. , Leiguarda Ramon , Robinson Robert G.
Published: January 2005

We present a consecutive series of 8 patients who developed a manic episode after a brain injury. Five patients had cortical lesions (4 with damage to the right basotemporal region, and 1 with bilateral damage to the orbitofrontal area). while the other 3 patients had subcortical lesions (white matter of the right frontal lobe, right anterior limb of the internal capsule, and right head of the caudate), a 18fluorodeoxyglucose positron emission tomography scan showed hypometabolism in the right lateral basotemporal region in all 3 patients. These findings suggest a major role for the basal region of the right temporal lobe in the modulation of mood.
Does adrenal graft enhance recovery of dopaminergic neurons in Parkinson's disease?
Authors: Hirsch E. C. , Duyckaerts C. , Javoy‐Agid F. , Hauw J.‐J , Agid Y.
Published: January 2005

A 54‐year‐old man with a 5‐year history of Parkinson's disease was treated with an autograft of adrenal medulla into the right caudate nucleus and died 4 months after surgery. Postmortem examination revealed that the graft was necrotic. It consisted mainly of reticulin and collagen fibrosis without catecholaminergic cell bodies identified either by immunohistochemistry or by situ hybridization with labeled human tyrosine hydroxylase (TH) cDNA probe. Sparse TH‐immunoreactive fibers, which did not stain for dopamine‐beta‐hydroxylase (DBH), ran through the graft. In contrast, intense staining for these catecholaminergic markers was found in the untransplanted adrenal medulla. Densely packed TH‐positive, DHB‐negative fibers were found in a restricted zone of the host striatum at the periphery of the graft. This effect was selective since the density of other neurons was not modified. The present study describes an additional patient in whom adrenal medulla autotransplantation failed to improve the parkinsonian disability. It suggests, however, that adrenal medulla grafts may stimulate the sprouting of striatal dopaminergic fibers in a limited zone of the grafted striatum.
Immunohistochemical study of cerebral amyloid angiopathy. III. Widespread alzheimer A4 peptide in cerebral microvessel walls colocalizes with gamma trace in patients with leukoencephalopathy
Authors: Vinters Harry V. , Secor Diana Lenard , Pardridge William M. , Gray Françoise
Published: January 2005

Brain tissue from 11 patients with cerebral amyloid angiopathy, changes of Alzheimer's disease, and variable degrees of subcortical leukoencephalopathy was examined by immunohistochemical methods, using primary antibodies to peptide segments representing portions of the Alzheimer A4 (beta‐) peptide or gamma‐trace peptide (seen most commonly in Icelandic patients with cerebral hemorrhage hereditary cerebral hemorrhage with amyloidosis {HCHWA‐I}). Variable A4 immunostaining was seen within cortical (and rarely white matter) parenchyma in the form of senile plaques (with or without central cores), and within capillary and arteriolar walls. Within individual patients, A4 deposits were often primarily parenchymal or vascular, and when they were arterior walls. Within individual patients, A4 deposits were often primarily parenchymal or vascular, and when they vascular they tended to be more prominent in arteriolar than in capillary wall segments. Perivascular A4 deposits were often detected around strongly immunoreactive microvessels. Gamma‐trace immunoreactivity was noted in many a4‐positive microvessel walls, but staining was always less intense than with the anti‐A4 antibody. We conclude that patients with severe cerebral amyloid angiopathy may show wide variastion in the severity and topography of A4 deposits within brain parenchyma. A4 may colocalize with gamma‐trace peptide, suggesting that A4 and gamma‐trace forms of cerebral amyloid angiopathy may not be as biochemically distinctive as has been suggested. Other proteases or protease inhibitors may contribute to the pathogenesis of cerebral amyloid angiopathy or cerebral amyloid angiopathy‐related stroke syndromes.
Hereditary motor and sensory neuropathies and hereditary spastic paraplegia: A magnetic stimulation study
Authors: Clays D , Waddy H. M. , Harding A. E. , Murray N. M. F. , Thomas P. K.
Published: January 2005

Central motor conduction to the small hand muscles was investigated in 59 patients with peroneal muscular atrophy and hereditary spastic paraplegia (HSP) by using transcranial magnetic brain stimulation. These comprised 20 patients with type I hereditary motor and sensory neuropathy (HMSN I), 15 with type II (HMSN II), 4 with HMSN I and 10 with HMSN II with associated pyramidal features, and 10 with the “pure” form of HSP. Central motor conduction was usually normal in HMSN I, HMSN II, and HSP. In HMSN I with pyramidal signs, central motor conduction time was greatly prolonged bilaterally. This result may reflect an associated involvement of the central motor pathways in these patients. In HMSN II with accompanying pyramidal features, 6 of the 10 patients had abnormal central motor conduction, although conduction times were only slightly prolonged, suggesting a different pathophysiological pattern.
Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson's disease
Authors: Mayberg Helen S. , Starkstein Sergio E. , Sadzot Bernard , Preziosi Thomas , Andrezejewski Paula L. , Dannals Robert F. , Wagner Henry N. , Robinson Robert G.
Published: January 2005

Depression is a frequent finding in patients with Parkinson's disease (PD). Regional cerebral glucose metabolism was measured in depressed and nondepressed patients with PD and in age‐comparable normal control subjects using 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET). Relative metabolic activity in the caudate and orbital‐inferior region of the frontal lobe was significantly lower in the depressed patients with PD as compared to both nondepressed patients and control subjects. There was a significant inverse correlation between relative glucose metabolism in the orbital‐inferior area of the frontal lobe and depression scores. This study suggests that depression in PD is associated with dysfunction in the caudate and orbital‐inferior area of the frontal lobe. This metabolic pattern is unlike that seen in patients with PD who have other behavioral deficits such as dementia, and suggests that disruption of basal ganglia circuits involving the inferior region of the frontal lobe may affect the regulation of mood.
Multiple sclerosis is prevalent in the zoroastrians (Parsis) of India
Authors: Wadia Noshir H. , Bhatia Kailash
Published: January 2005

Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bom‐ bay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona The age‐adjusted prevalence ratio for Bom‐ bay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States.
Stroke in pediatric acquired immunodeficiency syndrome
Authors: Park Yong D. , Belman Anita L. , Kim Tae‐Seung , Kure Katsuhiro , Llena Josefina F. , Lantos George , Bernstein Larry , Dickson Dennis W.
Published: January 2005

In a 4½‐year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs.
Axonal neuropathy with monoclonal IgG kappa that binds to a neurofilament protein
Authors: Nemni Raffaello , Feltri Maria L. , Fazio Raffaella , Quattrini Angelo , Lorenzetti Isabella , Corbo Massimo , Canal Nicholas
Published: January 2005

We report a 74‐year‐old woman with a slowly progressive sensory motor axonal neuropathy and a monoclonal IgG‐κ that bound to a 68‐kd axonal protein identified as the low molecular weight neurofilament protein. The sera of control subjects and disease controls did not bind to neurofilament protein.
Electroencephalography laboratory diagnosis of prolonged QT interval
Authors: Gospe Sidney M. , Gabor Andrew J.
Published: January 2005

Patients with prolongation of the QT interval are at risk for significant neurological morbidity and mortality secondary to ventricular tachyarrhythmias. These patients frequently undergo electroencephalographic (EEG) examination to evaluate episodes of loss of consciousness, which may be associated with convulsions. Electrocardiogram recording as a part of the EEG is a simple and common practice, but analysis for possible QT prolongation is not routinely performed by electroencephalographers. This is, in part, due to the fact that while calculation of the corrected QT interval is straight forward, a calculator is generally required. A nomogram that is presented simplifies determination of the corrected QT interval, facilitating diagnosis of prolongation of the QT interval in the EEG laboratory.
Treatment of spasticity with botulinum toxin: A double‐blind study
Authors: Snow Barry J. , Tsui Joseph K. C. , Bhatt Mohit H. , Varelas Michael , Hashimoto Stanley A. , Calne Donald B.
Published: January 2005

We studied the effect of botulinum‐A toxin on spasticity of the leg adductors in 9 patients who were either chair‐bound or bed‐bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double‐blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93‐0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care(p = 0.009). There were no adverse effects during this shortterm trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions.
Hypoglycemia alters striatal amino acid efflux in perinatal rats: An in vivo microdialysis study
Authors: Silverstein Faye S. , Simpson Jennifer , Gordon Kevin E.
Published: January 2005

In adult brain, during insulin‐induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin‐induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2‐hour recovery period, in each animal a 30‐minute baseline sample was obtained. Then insulin (0.6 μ/Kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level < 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre‐column derivatization with o‐Phthaldialdehyde, dialysate samples were assayed by high‐pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 ± 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 ± 5% of baseline, P = 0.002, ANOVA), and taurine efflux increased (up to 310 ± 120% of baseline; p < 0.06, ANOVA). In contrast with 9‐to 12‐fold increases in aspartate efflux reported in adult striatum, asparate efflux increased only slighty (to 174 ± 69% of baseline; not significant). In immature rodent brain, overall trends in striatal amino acid efflux during hypoglycemia are similar to patterns reported in adult animals; however, there are major differences in the timing, duration, and magnitude of these responses.
HTLV‐I sequences are not detected in peripheral blood genomic DNA or in brain cDNA of multiple sclerosis patients
Authors: Oksenberg Jorge R. , Mantegazza Renato , Sakai Koichiro , Bernard Claude C. A. , Steinman Lawrence
Published: January 2005

Human T‐cell lymphotropic virus (HTLV‐I) was recently reported to be etiologically associated with multiple sclerosis (MS). Genomic DNA from peripheral blood lymphocytes and brain plaques of patients with MS was analyzed for the presence of sequences homologous to the HTLV‐I pol gene using the polymerase chain reaction and dot blot techniques. Comparison of DNA amplification patterns between patients with MS, and with control subjects who have other autoimmune conditions, with those in healthy control subjects and with an HTLV‐I‐infected cell line indicates that HTLV‐I pol sequence is not present in the peripheral blood of patients with MS, and that the virus is not active in MS brain plaques.
Dystrophin analysis in duchenne and becker muscular dystrophy carriers: Correlation with intracellular calcium and albumin
Authors: Morandi L. , Mora M. , Gussoni E. , Tedeschi S. , Cornelio F.
Published: January 2005

Immunocytochemical localization and immunoblot analysis of dystrophin in muscle fibers of 11 obligate and probable, and 7 possible carriers of Duchenne and Becker muscular dystrophy revealed an abnormal expression of the protein in 3 of them. Localization of calcium and albumin, as endogenous markers of extracellular fluid penetration, showed the presence of both molecules inside some fibers lacking dystrophin. Our morphological studies show that the initial stages leading to fiber necrosis in Duchenne muscular dystrophy are present in carriers with mosaicism. Comparison of dystrophin studies with restriction fragment length polymorphism analysis and creatine kinase levels showed that neither immunocytochemical nor immunoblot techniques for dystrophin are sensitive enough to provide a basis for genetic counseling.
Elevated soluble interleukin‐2 receptor levels in patients with active multiple sclerosis
Authors: Adachi Keiko , Kumamoto Toshihide , Araki Shukuro
Published: January 2005

The level of soluble interleukin‐2 receptor (sIL‐2R) was quantitated with enzyme‐linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL‐2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL‐2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL‐2R level may be useful in evaluating disease activity in patients with multiple sclerosis.
Cerebrospinal fluid immune complexes in patients exposed to Borrelia burgdorferi: Detection of Borrelia‐specific and ‐nonspecific complexes
Authors: Coyle P. K. , Schutzer Steven E. , Belman Anita L. , Krupp Lauren B. , Golightly Marc G.
Published: January 2005

We analyzed cerebrospinal fluid (CSF) from 32 patients with neurological symptoms and evidence of Borrelia burgdorferi infection (29 were seropositive as determined by enzyme‐linked immunosorbent assay, 2 were cell‐mediated immune positive, and 1 had been seropositive as shown by enzyme‐linked immunosorbent assay 9 months previously). CSF immune complexes were found in 22 (69%) of 32 patients; in 18, there was sufficient sample to isolate immune complexes. By enzyme‐linked immunosorbent assay, isolated immune complexes from 10 of these 18 patients contained antibody specific for B. burgdorferi antigens. The isotypes were IgG (n = 8), IgM (n = 3), and IgA (n = 2). By immunoblot, these antibodies were directed against B. burgdorferi 41‐kDa antigen and occasionally against the 33‐ and 17‐kDa antigens. Anti–B. burgdorferi IgM was present in patients with acute neurological symptoms, was predominantly complexed rather than free, and decreased with clinical recovery in the one serial study. Three patients were nonreactive for free CSF antibodies, but had complexed antibodies to the organism. The preliminary finding of specific B. burgdorferi components in immune complexes in CSF suggests an active process triggered by the organism, even in the absence of other CSF abnormalities.
In vivo 1H spectroscopy of the human brain following electroconvulsive therapy
Authors: Woods Bryan T. , Chiu Tak‐Ming
Published: January 2005

Recent advances in the methodology of magnetic resonance spectroscopy now permit localized proton (1H) spectroscopy of the human brain in clinical magnetic resonance systems. In this study, localized 1H spectroscopy was used to observe directly the stimulation of brain metabolic activity in patients undergoing electroconvulsive theraphy (ECT) and to compare results obtained before and after treatments. Persistent increases in lactate were expected on the basis of animal data but these increases were small and equivocal 1 hour after ECT. In contrast, a large increase in a lipid signal from before to after ECT was observed in 5 patients when short echo times were used. We postulate that a significant portion of this lipid signal is related to maximal activation of the phosphatidylinositol second messenger system by single seizures, and that the sustained postictal effects of activation of the phosphatidylinositol system (increased levels of diacylglycerol and free fatty acids) have generalized inhibitory effects potentially relevant to both the clinical pathophysiology of seizures and the efficacy of ECT in major affective disorders.
Common T‐cell receptor Vβ usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis
Authors: Lee Soon Jin , Wucherpfennig Kai W. , Brod Staley A. , Benjamin Deborah , Weiner Howard L. , Hafler David A.
Published: January 2005

T‐cell populations were investigated in the blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Individual T cells were directly cloned from the cerebrospinal fluid and blood before in vitro expansion, and their clonotypes were compared by Southern blot analysis of the rearrangement patterns of their T‐cell receptor β chain and γ chain genes. This allowed the determination of whether two T cell clones shared the same T‐cell receptor and thus arose from identical, clonally expanded (oligoclonal) progenitor T cells. As an extension of previous studies, oligoclonal T‐cell clones were identified in both cerebrospinal fluid and blood populations in 5 of 9 patients with inflammatory demyelinating disease among a total of 486 blood and cerebrospinal fluid T‐cell clones. In contrast, no clonally expanded T‐cell populations were found among a total of 424 clones derived from either blood of 4 normal control subjects or blood and cerebrospinal fluid of 8 patients with other neurological diseases. Analysis of T‐cell receptor Vβ genes among 4 oligoclonal T‐cell populations derived from 3 patients with multiple sclerosis demonstrated common usage of the Vβ12 gene segment. These data suggest that oligoclonal T cells share similar specificities and that clonal expansion may have resulted from specific stimulation by an antigen. Moreover, identical clones between blood and cerebrospinal fluid were observed in 3 of 9 patients with demyelinating disease, thus providing further evidence of an equilibrium between peripheral and central nervous system immune compartments.
Major differences in the dynamics of primary and secondary progressive multiple sclerosis
Authors: Thompson Alan J. , Kermode A. G. , Wicks D. , MacManus D. G. , Kendall B. E. , Kingsley D. P. E. , McDonald W. I.
Published: January 2005

In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated. In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid–enhanced MRI over a 6‐month period. The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced. Enhancement also occurred within and at the edge of preexisting lesions. In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced. There was no difference in the degree of clinical deterioration between the two groups over the 6‐month period. These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.
Loss of chromosome 22 alleles in human sporadic spinal schwannomas
Authors: Fontaine Bertrand , Hanson Mark P. , Von Sattel Jean Paul , Martuza Robert L. , Gusella James F.
Published: January 2005

Acoustic neuromas occur either as sporadic solitary tumors in the general population or as inherited bilateral tumors typically in patients with neurofibromatosis type 2. Loss of heterozygosity for markers on the long arm of chromosome 22 has been reported in both instances, and neurofibromatosis type 2 has been genetically linked to a marker on the long arm of this autosome, suggesting that a unique locus on chromosome 22 is implicated in tumorigenesis of both sporadic and inherited acoustic neuromas. To determine whether the locus for neurofibromatosis type 2 might also be responsible for tumorigenesis of those schwannomas distinct from acoustic neuromas in people without neurofibromatosis type 2, we studied the DNA content of three sporadic spinal schwannomas. In all three, we found loss of heterozygosity for at least three markers on the long arm of chromosome 22, indicating a partial or total monosomy 22 in the tumor. Our results suggest that a locus on chromosome 22 is responsible for tumorigenesis in schwann cells regardless of their location in the central nervous system, and that some other mechanism (genetic or nongenetic) might account for the relative high proportion of schwannomas developing from the eighth cranial nerve.
Heterogeneity of the T‐cell receptor β gene rearrangements generated in myelin basic protein‐specific T‐cell clones isolated from a patient with multiple sclerosis
Authors: Richert John R. , Robinson Bs Eve D. , Johnson Armead H. , Bergman Cynthia A. , Dragovic Ljubo J. , Reinsmoen Nancy L. , Hurley Carolyn Katovich
Published: January 2005

Seventeen T‐cell clones derived from the peripheral blood of a patient with multiple sclerosis and reactive with a synthetic peptide corresponding to residues 152–170 of the human myelin basic protein molecule were previously shown to be cytotoxic for myelin basic protein‐coated target cells. Genetic restriction studies have now demonstrated that these clones recognize myelin basic protein in association with human leukocyte antigen DRw13. Studies of the T‐cell receptor β gene rearrangements generated by these clones demonstrated 12 different patterns, as evaluated by Southern blot analysis. Thus, the human T‐cell response to myelin basic protein is exceedingly heterogeneous, even among T cells that recognize the same small fragment of the molecule in association with the same class II restriction element.
BN rats do not reject F344 brain allografts even after systemic sensitization
Authors: Poltorak Maciej , Freed PhD William J.
Published: January 2005

Embryonic brain tissue allografts under many circumstances survive transplantation into the brain. It is generally believed that such grafts will not survive if the host animal is systemically sensitized, by skin grafting or other means, to major histocompatibility complex (MHC) antigens of the donor animal. We have found that F344 brain grafts survive in BN hosts even when the host is systemically sensitized to F344 tissue. Embryonic cerebral neocortex from F344 donors was transplanted into BN host rats (n = 95). Subsequently, the host rats were systemically sensitized with donor skin (n = 25), brain tissue (n = 41), or spleen cells (n = 6) and compared with a control group of rats consisting of allografts with no sensitization or sham procedures (n = 23). Rejection of the transplants in BN rat hosts was not provoked by any of the sensitization methods tested. Minor immunological responses that did not result in rejection were, however, present in many host animals. We did not observe infiltration of W3/13+ T cells and OX8+ cytotoxic lymphocytes in any of the groups. Nevertheless, substantial infiltrations of OX6+ antigen‐presenting cells and W3/25+ helper T cells were present. There was also an extensive enhancement of MHC class I immunoreactivity in parts of the grafted tissue developing within the third ventricle, but not for the same type of graft in the lateral ventricle. This increase of MHC class I expression was not accompanied by infiltration of cytotoxic T cells. Our findings thus suggest that neural graft rejection depends on general genetic susceptibility to immune reactions, particularly experimental allergic encephalomyelitis and not only on disparity between donor and host antigens encoded by the MHC. Moreover, enhancement of MHC class I and class II expression within transplanted tissue does not predict graft rejection.
Putative chromaffin cell survival and enhanced host‐derived TH‐Fiber innervation following a functional adrenal medulla autograft for Parkinson's disease
Authors: Kordower Jeffrey H. , Cochran Elizabeth , Penn Richard D. , Goetz Christopher G.
Published: January 2005

We report heretofore undescribed clinical and histological features of a patient with idiopathic Parkinson's disease who showed marked and persistent motoric benefit from an adrenal medulla autograft for 18 months following grafting. The patient returned to the preoperative level of disability prior to his death 30 months after implantation, the longest survival to date for an adrenal transplant. The graft site was primarily necrotic and large numbers of macrophages were still present at the time of death. A few tyrosine hydroxylase‐immunoreactive cells were found within the graft, providing the first evidence that adrenal medullary cells may be viable and produce catecholamines following human transplantation, A dense network of tyrosine hydroxylase‐immunoreactive terminals and processes was also seen ventral to the implant site and on both of its lateral borders. This response may represent sprouting by residual host dopaminergic neurons mediated by the vigorous response to injury displayed by the host striatum The relative paucity of surviving chromaffin cells, however, provides further evidence that adrenal medulla grafts survive poorly following intracerebral implantation, and factors other than dopamine replacement may be responsible for most of the functional effects observed following chromaffin cell transplantation.
Carbamazepine and phenytoin inhibit somatostatin release from dispersed cerebral cells in culture
Authors: Reichlin Seymour , Mothon Stella
Published: January 2005

To elucidate the mechanism by which carbamazepine lowers somatostatin concentration in cerebrospinal fluid of humans, the effect of carbamazepine on secretion of this peptide was studied in rat cerebral cell cultures. Concentrations of carbamazepine within the therapeutic range (4 × 10−5 M) inhibited spontaneous release of somatostatin and blocked secretory responses to the epileptogen, picrotoxin, and to the cyclic cAMP stimulator forskolin. One of the proposed mechanisms of carbamazepine action is that it binds to adenosine receptors, but in this study, aminophylline, an adenosine antagonist, in a concentration as high as 2.4 × 10−4 M, did not reverse carbamazepine effects. Carbamazepine suppression of picrotoxin, however, was overcome by exposure to veratridine, a sodium channel‐active compound. This finding supports the hypothesis that carbamazepine acts by binding to sodium channels. Phenytoin, another anticonvulsant with many similar properties, also blocked picrotoxin‐induced somatostatin release at a concentration of 10−4 M, and its effects were also reversed by veratridine at a concentration of 10−5 M. These findings clarify the mechanism by which carbamazepine and phenytoin act in epilepsy and trigeminal neuralgia.
In vivo magnetic resonance spectroscopy of brain and muscle in a type of mitochondrial encephalomyopathy (MERRF)
Authors: Matthews P. M. , Berkovic S. F. , Shoubridge E. A. , Andermann F. , Karpati G. , Carpenter S. , Arnold D. L.
Published: January 2005

Phosphorus magnetic resonance spectroscopy allows noninvasive measurement of the intracellular phosphate‐containing metabolites and intracellular pH in localized volumes of human muscle and brain in vivo. This technique was used to study 8 patients with a mitochondrial cytopathy (myoclonus epilepsy with ragged red fibers). Phosphorus magnetic resonance spectroscopy of resting gastrocnemius muscle demonstrated significantly increased relative intracellular inorganic phosphate concentrations (p < 0.0005) and decreased phosphocreatine to inorganic phosphate concentration ratios (p < 0.01) in the patients, although only 3 had myopathic signs or symptoms. We propose, therefore, that phosphorus magnetic resonance spectroscopy of resting skeletal muscle is a useful clinical test in evaluation of progressive myoclonus epilepsy. In contrast to results from muscle, however, the relative phosphate metabolite concentrations and intracellular pH in central volumes of the brains of these patients were normal, despite evidence from our previous positron emission tomography studies suggesting that there is diffuse impairment of cerebral oxidative metabolism.
Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography
Authors: Meyer E. , Ferguson S. S. G. , Zatorre R. J. , Alivisatos B. , Marrett S. , Evans A. C. , Hakim A. M.
Published: January 2005

In human primary somatosensory cortex, the cerebral blood flow response to vibrotactile stimulation of the fingers (110 Hz), as measured by positron emission tomography and H215O, was 13% higher (p < 0.025) when the subjects attended to the stimulus, compared to when they were simultaneously engaged in a distraction task. This suggests that the physiological response of a primary cortical area can be modulated by the attentive behavior of the subject.
The erythrocyte‐type glucose transporter in blood vessels of primary and metastatic brain tumors
Authors: Harik Sami I. , Roessmann Uros
Published: January 2005

We previously demonstrated that brain microvessels have a high density of the erythrocyte‐type glucose transporter and suggested this could be used as a marker of cells with “occluding” junctions. Now, we have studied by immunocytochemistry the tissue distribution of the glucose transporter in a variety of primary and metastatic human brain tumors with a monoclonal antibody to the glucose transporter of human erythrocytes. Microvessels in normal brain tissue distant from the tumor, and in brain surrounding the tumor, immunostained strongly for the glucose transporter. Microvessels in primary and metastatic tumors, however, lacked glucose transporter immunoreactivity. Only in the relatively benign juvenile cerebellar astrocytomas was glucose transporter immunoreactivity retained in some of the tumor microvessels. Because a high glucose transporter density is a marker of vessels with barrier properties, our results indicate that the vast majority of brain tumor microvessels do not have an intact blood‐brain barrier.
Epileptogenic effect of hypoxia in the immature rodent brain
Authors: Jensen F. E. , Applegate C. D. , Holtzman D. , Belin T. R. , Burchfiel J. L.
Published: January 2005

The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age‐dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0,2,3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40percnt; of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia‐induced epileptiform EEG changes was highest in the animals subjected to moderately hyoxic conditions (3% and 4percnt; oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia.
The time course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid administration of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐tetrahydropyridine to monkeys
Authors: Kurlan Roger , Kim Michael H. , Gash Don M.
Published: January 2005

We studied rhesus monkeys with hemiparkinsonism or bilateral parkinsonism produced by unilateral or bilateral intracarotid administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine. Using a standardized clinical rating scale, 4 hemiparkinsonian monkeys showed a 13 to 56% (mean, 36%) spontaneous improvement during an obsevation period of up to 25 weeks. Generally, recovery leveled off after 14 weeks. Four bilaterally parkinsonian monkeys showed a 5 to 42%(mean, 22percnt;) improvement over a period of up to 30 weeks. Our findings emphasize that spontaneous recovery is a potentially confounding characteristic of this monkey model when used for assessing novel antiparkinsonian therapies.