bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal disseminated hemorrhagic toxoplasmic encephalitis as the initial manifestation of AIDS
Authors: Wijdicks Eelco F. M. , Borleffs Jan C. C. , Hoepelman Andy I. M. , Jansen Gerard H.
Published: January 2005

A 28‐year‐old woman presented with progressive coma after being asymptomatic for 1 year after the demonstration of seropositivity for human immunodeficiency virus and high serum immunoglobulin G toxoplasma titers. Computed tomographic scanning showed multiple rounded cerebral hemorrhages and massive cerebral edema. Postmortem examination disclosed Toxoplasma gondii cysts scattered throughout the brain. An overwhelming fatal toxoplasmosis associated with multiple cerebral hemorrhages may be the first presentation of the acquired immunodeficiency syndrome. We raise the possibility that frequent neuroradiological monitoring may be indicated in asymptomatic human immunodeficiency virus–infected patients with high immunoglobulin G toxoplasma titers.
A controlled trial of propoxyphene and naltrexone in patients with tourette's syndrome
Authors: Kurlan Roger , Majumdar Lisa , Deeley Cheryl , Mudholkar Govind S. , Plumb Sandra , Como Peter G.
Published: January 2005

To investigate the effect of drugs acting on the endogenous opioid system, we studied 10 adults with Tourette's syndrome who received propoxyphene hydrochloride (260 mg/day), naltrexone hydrochloride (50 mg/day), and placebo in a double‐blinded, randomized clinical trial. Using a self‐report scale (Tourette's Syndrome Symptom List), subjects noted a significant (p < 0.04) lessening of tics after treatment with naltrexone when compared with placebo. An improvement in performance on the Trail Making B test, a measure of attention and visuomotor sequencing and planning, occurred after receiving naltrexone when compared with placebo (p < 0.08) or propoxyphene (p < 0.02). The Trail Making B test best discriminated the treatments (p < 0.02, analysis of variance). No other treatment effects were observed for several other measures of tic severity, attentional ability, or obsessive‐compulsive symptoms. Our findings indicate that pharmacological manipulation of the endogenous opioid system does influence symptoms of Tourette's syndrome.
Genetic linkage analysis of nerve growth factor (beta) in familial alzheimer's disease
Authors: Alberts Marchk J. , Pericak‐Vance Margaret A. , Royal Vernice , Bebout Jackie , Gaskell Peter , Thomas John , Hung Wu‐Yen , Clark Chris , Earl Nancy , Roses Allen D.
Published: January 2005

Recent studies have not shown linkage of late‐onset (mean age, >60 years) familial Alzheimer's disease (FAD) to the chromosome 21 locus reported linked to earlyonset FAD. Beta nerve growth factor (β‐NGF) has been considered a candidate gene in the pathogenesis and therapy of FAD, based on its localization in the cortex and hippocampus and its ability to enhance the growth and survival of cholinergic neurons. A 1.5‐kb fragment of the β‐NGF gene was used to detect a Bgl II restriction fragment length polymorphism, which was then used for linkage analysis. A total of 30 families (27 late onset) with 147 affected members were studied. Close linkage (θ < 0.03, z < −2.00) of late‐onset FAD with β‐NGF was excluded. Two apparent obligate crossovers between affected members were detected in different autopsy‐confirmed families. Based on these results, β‐NGF is not the gene responsible for late‐onset FAD in the families analyzed.
Na+‐Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter
Authors: Stys Peter K. , Waxman Stephen G. , Ransom Bruce R.
Published: January 2005

White matter of the mammalian central nervous system suffers irreversible injury after prolonged anoxia, which can result in severe neurological impairment. This type of injury is critically dependent on Ca2+ influx into cells. We present evidence that the Na+, Ca2+ exchanger mediates the majority of the damaging Ca2+ influx into cells during anoxia in white matter. Anoxic injury was studied in the isolated rat optic nerve, and functional recovery was monitored using the compound action potential. Blockers of voltage‐gated Na+ channels (tetrodotoxin and saxitoxin) significantly improved recovery, as did perfusion with zeroNa+ solution; both maneuvers would prevent intracellular [Na+] from rising and thus prevent Ca2+ influx by inhibiting reverse operation of the Na+, Ca2+ exchanger. Direct pharmacological blockade of the Na+, Ca2+ exchanger during anoxia with bepridil or benzamil also significantly improved recovery. These findings suggest that reverse operation of the Na+, Ca2+ exchanger during anoxia is a critical mechanism of Ca2+ influx and subsequent white matter injury.
Short‐chainL‐3‐hydroxyacyl‐CoA dehydrogenase deficiency in muscle: A new cause for recurrent myoglobinuria and encephalopathy
Authors: Tein I. , De Vivo D. C. , Hale D. E. , Clarke J. T. R. , Zinman H. , Laxer R. , Shore A. , Dimauro S.
Published: January 2005

We report on a 16‐year‐old girl with short‐chainL‐3‐hydroxyacyl‐coenzyme A (CoA) dehydrogenase deficiency resulting in juvenile‐onset recurrent myoglobinuria, hypoketotic hypoglycemic encephalopathy, and hypertrophic/dilatative cardiomyopathy. Urinary organic acids showed traces of 3‐hydroxy‐dodecanedioic acids and small amounts of suberic, sebacic, and adipic acids. There was a marked decrease inL‐3‐hydroxyacyl‐CoA dehydrogenase activity in muscle with acetoacetyl‐CoA as substrate (2.48 μmol/min/gm; normal = 6.90 ± 1.80 μmol/min/gm of tissue; n = 11), contrasting with normalL‐3‐hydroxyacyl‐CoA dehydrogenase activity with 3‐ketooctanoyl‐CoA and 3‐ketopalmitoyl‐CoA as substrates. Short‐chainL‐3‐hydroxyacyl‐CoA dehydrogenase activity was normal in fibroblasts, suggesting a tissue‐specific defect.
Presynaptic parkinsonism in olivopontocerebellar atrophy: Clinical, pathological, and neurochemical evidence
Authors: Pascual Julio , Pazos Angel , del Olmo Elena , Figols Javier , Leno Carlos , Berciano José
Published: January 2005

The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe a patient with olivopontocerebellar atrophy whose clinical presentation was levodopa‐responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H‐spiperone showed normal densities of D2 dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson's disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson's disease, nor does it exclude multiple‐system, atrophy‐related parkinsonism.
Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, san francisco, 1981–1989
Authors: Gillespie Sheila M. , Chang Yuan , Lemp George , Arthur Ray , Buchbinder Susan , Steimle Anthony , Baumgartner James , Rando Thomas , Neal Denesse , Rutherford George , Schonberger Lawrence , Janssen Robert
Published: January 2005

Progressive multifocal leukoencephalopathy (PML), a rare neurological disease, has been sporadically reported in persons infected with human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). From January 1981 through February 1989, in San Francisco, we identified 94 HIV‐infected persons with PML, of whom 48 (51%) were pathologically confirmed (as required for AIDS case reporting). These 48 patients were significantly older when diagnosed with AIDS (20% older than 50 years) than patients with AIDS without PML. The remaining 46 (49%) patients, diagnosed clinically and by neuroimaging, did not differ significantly from definitive patients in demographic or survival characteristics after PML diagnosis. We detected antibodies to JC virus, the causative agent of PML, in 9 of 14 (64%) AIDS‐related patients with PML, and in 9 of 14 (64%) matched control subjects, suggesting that determination of JC virus antibody status before AIDS diagnosis does not reliably indicate which patients will contract PML. Our study shows that the proportion of patients with AIDS who contracted PML remained stable between 1981 and 1988, but increased in the first 2 months of 1989. Our findings further indicate that PML in HIV‐infected patients may be underestimated by as much as 50%.
Expression patterns of β‐amyloid precursor protein (β‐APP) in neural and nonneural human tissues from alzheimer's disease and control subjects
Authors: Arai Hiroyuki , Lee Virginia M.‐Y. , Messinger Meridith L. , Greenberg Barry D. , Lowery David E. , Trojanowski John Q.
Published: January 2005

Both neural and nonneural human tissues from patients with or without Alzheimer's disease (AD) were surveyed to detect the presence of the β‐amyloid protein and its precursors. This was accomplished using polyclonal and monoclonal antibodies to epitopes in the 695 amino acid long β‐APP (i.e., β‐APP695), as well as in related β‐APPs. Immunoreactivity in β‐APP in brain was prominent in senile plaques, extraneuronal tangles, and neurons. Outside the brain, β‐APP staining was seen in neurons and satellite glial cells of the dorsal root, enteric and trigeminal gangila, the adeno‐and neurohypophysis, megakaryocytes, and adrenal gland in samples from patients with AD and those without AD. Western blots of neocortex revealed three major proteins with apparent molecular masses of 105, 115, and 125 kDa in the insoluble membrane‐associated fractions, while two broad bands with a molecular weight centered at about 100 and 120 kDa were detected in soluble fractions. In addition, the pituitary and adrenal glands as well as cardiac muscle revealed prominent immunobands in membrane‐associated fractions. Notably, other nonneural tissues were devoid of β‐APP immunoreactivity. Thus, the β‐APPs are detectable only in a limited number of nonneural tissues. Taken together, these data suggest that β‐APPs produced in the brain are sources of β‐APP peptides that accumulate as senile plaques in AD.
Codon 618 variant of alzheimer amyloid gene associated with inherited cerebral hemorrhage
Authors: Fernandez‐Madrid Ivan , Levy Efrat , Marder Karen , Frangione Blas
Published: January 2005

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA‐D) is an autosomal dominant form of severe cerebrovascular amyloid angiopathy causing recurrent strokes during the fifth and sixth decades of life. The major constituent of the amyloid deposits in HCHWA‐D is the amyloid β‐protein (Aβ), also found in Alzheimer's disease. A point mutation in the DNA sequence encoding Aβ has been found in 2 unrelated patients with HCHWA‐D, and an assay detecting the single base change was developed for diagnostic purposes. We describe the detection of the point mutation in a patient living in the United States, suffering from recurring cerebral hemorrhages, who only recently was diagnosed with HCHWA‐D. In addition, we tested a number of family members, and found the mutation in 2 additional individuals, one of them too young to exhibit clinical manifestations. This study combined with the study of two other families in Holland indicates that the codon 618 variant in the amyloid precursor protein gene segregates with HCHWA‐D.
Reflex activity and muscle tone during elbow movements in patients with spastic paresis
Authors: Dietz V. , Trippel M. , Berger W.
Published: January 2005

Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis. During sinusoidal (0.3‐Hz) isometric or isotonic elbow tracking, with a control either of joint position or of torque, randomly timed displacements were induced (at one of three velocities) stretching either the activated flexor or the extensor muscles. On the spastic side, exaggerated short‐latency reflexes were apparent, but in contrast, the amplitude of long‐latency electromyography (EMG) responses was reduced. The latter responses were differentially modulated on the unaffected side, predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque, while the mode of muscle contraction (isometric or isotonic) had little influence on this behavior. This difference in reflex modulation was lost on the spastic side. The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements. The ratio of torque to EMG activity during displacements was higher for both background and reflex‐induced EMG on the spastic limb than on the unaffected side. This effect was more pronounced for the flexor than for the extensor muscles. Consequently, the development of spastic muscle hypertonia cannot be attributed to an increase in EMG activity. It is suggested that secondary to a supraspinal lesion, mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched.
Parkinsonian bradykinesia is due to depression in the rate of rise of muscle activity
Authors: Godaux E. , Koulischer D. , Jacquy J.
Published: January 2005

Parkinsonian bradykinesia is defined by a slowness in the execution of movement. We studied the pathophysiology of this symptom in rapid arm‐reaching movements to a visual target carried out in a reaction‐time task. The major cause of bradykinesia was found to be depression in the rate of rise of electromyographic activity. The amplitude of the peak of this activity did not change significantly. There was no change either in the sequential activation of muscles, in the amount of co‐contraction activity, in the accurary of aim toward the visual target, or in the movement trajectory.
Parietal lobe epilepsy: Diagnostic considerations and results of surgery
Authors: Williamson P. D. , Boon P. A. , Thadani V. M. , Darcey T. M. , Spencer D. D. , Spencer S. S. , Novelly R. A. , Mattson R. H.
Published: January 2005

Eleven patients, evaluated between 1983 and 1988, with parietal lobe seizure origin as determined by circumscribed lesion detection in all and successful surgery in 10, were retrospectively evaluated in terms of clinical seizure characteristics and electroencephalographic (EEG) findings. Seven of 11 patients reported auras prior to seizures. In 4 patients, auras were lateralized somatosensory sensations, but in 1 they were ipsilateral to the side of seizure origin, and in 2 they had only occurred many years previously when seizures began. Other auras were either nonspecific or suggested seizure origin outside of the parietal lobe. Observed seizures were of two types: asymmetrical tonic seizures with or without clonic activity and complex partial seizures with loss of contact and automatisms. Four patients had only the first type of seizure and an equal number had only the second type. Three patients had both types of seizures during different episodes. Scalp EEGs correctly localized the side and region of seizure onset in only 1 patient. Three additional patients with congruent parietal localization on scalp EEG had additional misleading EEG findings. All patients had lesions detected with neuroimaging, but in 5 this detection occurred after they had been initially evaluated. These 5 patients had intracranial EEG studies designed to localize the region of seizure origin, and correct seizure onset localization was achieved in 2. Of the other 3 patients, false localization occurred in 1, and 2 could not be localized. Four patients with known lesions and 2 of the patients in whom lesions were detected after initial intracranial evaluations were studied with subdural grid electrodes placed over the lesions. Seizures were recorded during monitoring in all 6 patients, but seizure origin was well localized in only 1. One patient with false localization had a temporal lobectomy, and 2 unlocalized patients had partial corpus callosotomies. Surgery was ineffective in all 3. Surgery aimed at lesion resection in 10 patients (including 2 who had had preious procedures) resulted in all 10 patients becoming seizure‐free with minimal or no neurological deficits. We conclude that (1) a syndrome of parietal lobe epilepsy based on clinical and scalp EEG findings could not be defined in this series of 11 patients; (2)intracranial EEG findings are often not helpful and sometimes misleading, even when parietal lesions are known or suspected; (3) when circumscribed parietal lobe lesions are detected they are the cause of the patient's seizures regardless of seizure type and EEG findings; and (4) guided by the results of functional mapping, parietal lobe lesions can be safely resected with excellent surgical results.
Localization of extratemporal epileptic foci during ictal single photon emission computed tomography
Authors: Marks David A. , Katz Amiram , Hoffer Paul , Spencer Susan S.
Published: January 2005

We obtained single photon emission computed tomography (SPECT) scans with technetium‐99M‐hexamethyl‐propylene‐amine‐oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci.
Cortically evoked motor responses in patients with Xp22.3‐linked Kallmann's syndrome and in female gene carriers
Authors: Danek Adrian , Heye Babett , Schroedter Robert
Published: January 2005

Patients with Kallmann's syndrome show hypothalamic hypogonadism, hyposmia, and congenital mirror movements. As a correlate, a defect of gonadotropic neuron migration into the brain was recently detected. Considering abnormal outgrowth of neurons also as a possible substrate underlying mirror movements, we studied 3 patients and 2 asymptomatic female gene carriers from a kindred with proven linkage to Xp22.3, using focal transcranial magnetic stimulation of motor cortex hand areas with a figure‐eight coil. In all 3 affected brothers, bilateral responses could be evoked almost simultaneously in their thenar muscles (slight latency differences were statistically insignificant). In contrast, the mother and the maternal aunt showed only unilateral, normal thenar responses, even with maximum tolerable stimulator output and high signal amplification. Correspondingly, mirror movements were present in the patients, but not in the gene carriers. Bilaterality of cortically evoked hand muscle responses and mirror movements, therefore, behaved as X‐chromosomal recessive traits. A likely cause might be a disorder of neuronal outgrowth in the motor system, particularly of inhibitory callosal fibers. For normal anatomical development of the motor system, one intact Xp22.3 gene seems necessary.
Electroconvulsive therapy treatment of depression in a patient with adult GM2 gangliosidosis
Authors: Renshaw Perry F. , Stern Theodore A. , Welch Charles , Schouten Ronald , Kolodny Edwin H.
Published: January 2005

Adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underlying gangliosidosis. We report the successful use of electroconvulsive therapy for treatment of severe depression in a young man with adult GM2 gangliosidosis.
Chronic neuroleptic treatment: D2 dopamine receptor supersensitivity and striatal glutamatergic transmission
Authors: Calabresi Paolo , De Murtas Marco , Mercuri Nicola Biagio , Bernardi Giorgio
Published: January 2005

We studied the in vitro electrical activity of rat neostriatal neurons following chronic neuroleptic treatment. In haloperidol‐treated rats, unlike naive animals, activation of neostriatal D2 dopamine receptors induced a potent presynaptic inhibition of glutamate‐mediated excitatory synaptic potentials. Haloperidol treatment did not affect the intrinsic membrane properties of the neostriatal neurons. Pre‐ and postsynaptic physiological responses to direct and indirect gamma‐aminobutyric acid (GABA)–ergic and cholinergic agonists were not affected by chronic haloperidol treatment. These findings suggest that movement disorders induced by chronic neuroleptic treatment may result, at least in part, from a hypersensitivity of presynaptic D2 dopamine receptors regulating the release of glutamate.
Motor dyscontrol in narcolepsy: Rapid‐eye‐movement (REM) sleep without atonia and REM sleep behavior disorder
Authors: Schenck Carlos H. , Mahowald Mark W.
Published: January 2005

Narcolepsy involves abnormalities of rapid‐eye‐movement (REM) sleep, including a short latency to the onset of REM sleep, hypnagogic hallucinations, and sleep paralysis. In addition, persistence of muscle tone by electromyographic criteria or excessive muscle twitching during REM sleep or both have been reported in treated and untreated narcoleptic patients. We report that another previously described abnormality of REM sleep, REM sleep behavior disorder, may also be a symptom of narcolepsy. This disorder was found in 10 narcoleptic patients during routine clinical evaluations involving polysomnography and multiple sleep latency tests. During REM sleep, 7 additional narcoleptic patients displayed persistent muscle tone and/or excessive twitching, which we believe to be subclinical components of REM sleep behavior disorder. These 17 patients, diagnosed by established criteria for narcolepsy and for REM sleep behavior disorder, ranged in age from 8 to 74 years. Seventy‐one percent were male. Narcolepsy and REM sleep behavior disorder most commonly emerged in tandem. In 3 patients, treatment of narcolepsy‐cataplexy with stimulants and tricyclics either induced or exacerbated REM sleep behavior disorder.
L‐2‐hydroxyglutaric acidemia: A novel inherited neurometabolic disease
Authors: Barth Peter G. , Hoffmann Georg F. , Jaeken Jaak , Lehnert Willy , Hanefeld Folker , Van Gennip Albert H. , Duran Marinus , Valk Jaap , Schutgens Ruud B. H. , Trefz Friedrich K. , Reimann Gabriele , Hartung Hans‐Peter
Published: January 2005

Routine screening for organic acids revealed increased and isolated urinary excretion of L‐2‐hydroxyglutaric acid in 8 mentally retarded patients from five unrelated families, including three pairs of siblings. L‐2‐Hydroxyglutaric acid concentration was also found to be increased in the cerebrospinal fluid (CSF) and to a lesser extent in plasma. The only other biochemical abnormality was an increased concentration of lysine, both in plasma and in CSF. No organic acid abnormality was found on screening of asymptomatic family members. Patients were of either sex, and became symptomatic during childhood, with moderate to severe mental deficiency in all and definite cerebellar dysfunction in 7. Magnetic resonance imaging revealed an identical abnormal pattern with subcortical leukoencephalopathy, cerebellar atrophy, and signal changes in the putamina and dentate nuclei, in all patients. No specific biochemical function or catabolic pathway involving L‐2‐hydroxyglutaric acid is known in mammals, including humans. Preliminary loading and dietary studies failed to reveal the origin of the compound. The elevated CSF/plasma ratio suggests that it is in part generated within the central nervous system. This report describes a novel inherited neurometabolic disease, probably autosomal recessive, with distinct clinical, biochemical, and neuroimaging features.
Spontaneous remission of a third‐nerve palsy in meningeal lymphoma
Authors: Galetta Steven L. , Sergott Robert C. , Wells Gregg B. , Atlas Scott W. , Bird Shawn J.
Published: January 2005

We report on a patient with spontaneous remission of a third‐nerve palsy who was subsequently found to have meningeal lymphoma. Initial magnetic resonance images (MRI) showed bilateral enhancement of the third nerves. Follow‐up MRI 7 months later, without treatment, showed complete resolution. One year after initial presentation, the patient developed multiple lumbosacral radiculopathies and examination of a nerve root biopsy specimen disclosed a B‐cell lymphoma. Serial cerebrospinal fluid analyses over the previous year showed occasional atypical cells, later found to resemble closely the biopsy cell type. We conclude that meningeal lymphoma may have a protracted course, with spontaneous remission of both clinical and neuroimaging findings.
Detection of Epstein‐Barr virus in the brain by the polymerase chain reaction
Authors: Pedneault Louise , Katz Ben Z. , Miller George
Published: January 2005

Epstein‐Barr virus (EBV) has been implicated in a variety of central nervous system syndromes. In a few well‐studied patients, EBV has been detected by viral isolation or EBV DNA has been found by Southern hybridization analysis. Using polymerase chain reaction, we evaluated brain biopsy specimens from 24 patients for the presence of EBV genomes. EBV DNA was found in brain specimens from 18 patients in whom presence of the virus in the brain was suspected clinically or on the basis of serological tests. Six patients had acquired immunodeficiency syndrome; 2 were kidney transplant recipients. Brain specimens from 4 patients with encephalitis due to other herpes group viruses and from a patient with metabolic encephalopathy were negative for EBV DNA as determined by polymerase chain reaction. The findings indicate a need to evaluate the role of EBV in diverse neurological syndromes, especially those occurring in immunodeficient hosts.
The persistent vegetative state in children: Report of the child neurology society ethics committee
Authors: Ashwal Stephen , Bale James F. , Coulter David L. , Eiben Robert , Garg Bhuwan P. , Hill Alan , Myer Edwin C. , Nordgren Richard E. , Shewmon D. Alan , Sunder Theodore R. , Walker Russell W.
Published: January 2005

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% belived that this applied to infants younger than 2 months and 70% in the 2‐month to 2‐year group; (2) a period of 3 to 6 months was belived to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4,1;2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% “never” withhold fluid and nutrition from infants and children in a PVS and 28% “always” give medication for pain and suffering. The data suggest that child neurologists believe PVS can be diagnosed in children after 2 years of age, but that in younger children a more cautious approach is indicate. The findings suggest reasonable agreement concerning many of these issues, and it may be possible at this time to develop a position statement on the medical aspects of PVS in children.
HTLV‐I‐specific cytotoxic T lymphocytes in the cerebrospinal fluid of patients with HTLV‐I‐associated neurological disease
Authors: Jacobson Steven , McFarlin Dale E. , Robinson Susan , Voskuhl Rhonda , Martin Roland , Brewah Alfred , Newell Amy J. , Koenig Scott
Published: January 2005

Recently, it has been shown that in patients with human T‐cell lymphotropic virus type I (HTLV‐I)–associated neurological disease, high levels of HTLV‐I–specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood. These CTLs predominantly recognized products of the pX region of HTLV‐I, had a CD8+ phenotype, and were human leukocyte class I restricted. Moreover, these responses were not detected in asymptomatic, HTLV‐I–seropositive individuals. This implied a role for these CTLs in the pathogenesis of the neurological disorder associated with HTLV‐I. We have extended these observations by demonstrating HTLV‐I–specific CTLs directly from lymphocytes obtained from the cerebrospinal fluid of patients with HTLV‐I–associated myelopathy/tropical spastic parapare‐sis. Uncultured cerebrospinal fluid lymphocytes were used directly as effectors on a variety of targets expressing HTLV‐I. These cells were lysed in a virus‐specific and HLA class I‐restricted manner. Moreover, the cerebrospinal fluid lymphocytes were sorted into purified CD8+ populations, cloned by limiting dilution, and assayed for CTL activity. An exceedingly high proportion of these resultant lines were shown to be cytolytic and precursor frequency analysis indicated that as many as 1 in 500 cells were HTLV‐I–specific CTLs. The majority of these CTL lines recognized HTLV‐I gene products encoded within the pX region of HTLV‐I. The significance of these HTLV‐I–specific CTLs in the central nervous system of patients with HTLV‐I–associated neurological disease is discussed with regard to the potential role of CTLs in the pathogenesis of this disease.
No evidence for spumavirus or oncovirus infection in relapsing–remitting multiple sclerosis
Authors: Svenningsson Anders , Lycke Jan , Svennerholm Bo , Gronowitz Simon , Andersen Oluf
Published: January 2005

Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T‐cell lymphotropic virus types I {HTLV‐I} and II {HTLV‐II}) in multiple sclerosis. Eleven patients with relapsing‐remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV‐I), and pol (HTLV‐II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.
Using gadolinium‐enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis
Authors: McFarland Henry F. , Frank Joseph A. , Albert Paul S. , Smith Mary E. , Martin Roland , Harris Jonathan O. , Patronas Nicholas , Maloni Heidi , McFarlin Dale E.
Published: January 2005

The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing‐remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)‐enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd‐enhanced lesions as the outcome measure. Frequent (>1/mo) Gd‐enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd‐enhancing lesions as an outcome measure in a clinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd‐enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS.
Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity
Authors: Bicknese Alma R. , May William , Hickey William F. , Dodson W. Edwin
Published: January 2005

Four unrelated children were thought to have valproate‐associated hepatotoxicity. They presented with recurrent partial secondarily generalized status epilepticus and epilepsia partialis continua followed by mental and motor regression. Despite treatment with multiple antiepileptic medications, they continued to have seizures. After initiation of valproic acid (VPA), all 4 manifested liver failure within 3 months. Two of these children each had 1 sibling who was not exposed to VPA, but who developed the same clinical picture including liver failure. At the time of autopsy, all 6 children had similar neuropathological findings with focal areas of spongiosis and neuronal loss, diffuse gliosis, and Alzheimer type II cells. One VPA‐treated patient underwent a successful liver transplantation only to die from relentlessly progressive neurological deterioration. We propose that many of the reported patients with VPA‐associated hepatotoxicity represent undiagnosed patients with early childhood hepatocerebral degeneration, the Huttenlocher variant of Alpers' syndrome. This disease manifests by obstinate partial seizures, recurrent partial secondarily generalized status epilepticus, epilepsia partialis continua, psychomotor deterioration, and hepatic dysfunction that is exacerbated by VPA administration. The accelerated demise from liver failure in the nontransplanted patients before the central nervous system pathology fully evolves makes the diagnosis of this rare condition difficult. The occurrence of disease in the unexposed siblings suggests recessive inheritance.
Temporal lobectomy for uncontrolled seizures: The role of positron emission tomography
Authors: Theodore William H. , Sato Susumu , Kufta Conrad , Balish M. B. , Bromfield E. B. , Leiderman Deborah B.
Published: January 2005

We evaluated the role of positron emission tomography (PET) with [18F]deoxyglucose (FDG) (FDG‐PET) for planning surgery in 53 patients who had temporal lobectomy for uncontrolled seizures at the National Institutes of Health from 1981 to 1990. Investigators blinded to PET data used results of telemetered video‐electroencephalographic ictal monitoring and other standard criteria to decide whether subdural electrodes (22 patients, i.e., the “invasive” group) should be implanted or surgery performed. PET scans were analyzed using a standard regional template. Mean lateral but not mesial temporal asymmetry was significantly higher in patients who became seizure free (p < 0.03). Patients with ≤ 15% hypometabolism were significantly more likely to be seizure free in the entire study population and the invasive subgroup. Visual identification of hypometabolism was less accurate. When a clear temporal ictal surface electroencephalographic focus was present, FDG‐PET provided less additional information. FDG‐PET may be particularly valuable if the surface electroencephalographic scan is nonlocalizing. In addition to helping to identify the seizure focus, it may allow limitation of invasive electrode placement to those necessary for functional mapping. When PET is used to identify epileptic foci, quantitative measurements of asymmetry should be made.
Large focal tumor‐like demyelinating lesions of the brain: Intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients
Authors: Kepes John J.
Published: January 2005

Thirty‐one patients with large, focal cerebral demyelinating lesions are reported. Twenty‐four patients had solitary lesions and 7 had multiple foci, the latter apparently of identical age. The lesions presented clinically and radiologically as brain tumors (gliomas or metastases) or as multiple cysts. Six patients were older than 57 years (2 in their 70s) at the onset of their symptoms. The demyelinating nature of the lesions was established through biopsy in each patient and all improved significantly after corticosteroid therapy. Three patients developed additional lesions during the follow‐up periods ranging from 9 months to 12 years consistent with the course of multiple sclerosis. Twenty‐eight patients did not develop additional lesions. These included 6 patients with multiple lesions at the onset. In 1 of the patients, the first symptoms developed 10 days after receiving vaccination against influenza. Two patients had concomitant malignancy (chronic monomyelogenous leukemia and retroperitoneal seminoma respectively) and 1 patient developed immunoblastic sarcoma in the opposite hemisphere after biopsy diagnosis and steroid treatment of her demyelinating lesion. Tumor‐like masses of demyelination may occupy an intermediate position between multiple sclerosis and postinfectious/postvaccination encephalitis. The clinical course (history of vaccination in one instance, acute onset, good response to corticosteroids, no clinical or radiological evidence of new lesions in the great majority of patients) favored postinfectious/postvaccination encephalitis. Lesion size however greatly exceeded that of the small foci of perivenous demyelination seen in typical postinfectious/postvaccination encephalitis and tended to present as space‐occupying masses.
Multiple sclerosis: Remyelination of nascent lesions: Remyelination of nascent lesions
Authors: Prineas J. W. , Barnard R. O. , Kwon E. E. , Sharer L. R. , Cho E.‐S.
Published: January 2005

The relationship between plaque pathology and disease duration was examined in 15 patients with multiple sclerosis who died early in the course of their illness. Myelin‐stained sections revealed that most plaques examined in patients who died during the first month of their illness showed evidence of ongoing myelin destruction accompanied by a loss of oligodendrocytes. Plaques containing large numbers of oligodendrocytes were not observed in these patients, but were relatively common in patients who died more than 1 month after clinical onset. Remyelination affecting more than 10% of the plaque area was observed in 3 of 82 plaques in 5 patients who died within 10 weeks of clinical onset, in 38 of 105 plaques in 5 patients who died 3 to 10 months after clinical onset, and in 19 of 92 plaques in 5 patients who died 18 months or longer after clinical onset. The study provides new evidence that both oligodendrocytes and myelin are destroyed in new lesions, that this activity ceases completely in many lesions within a few weeks, and that remyelination frequently ensues following repopulation of the plaque by oligodendrocytes. The findings suggest that new lesions normally remyelinate unless interrupted by recurrent activity and that remyelinated shadow plaques are the outcome of a single previous episode of focal demyelination.
“Signing tics”—insights into the pathophysiology of symptoms in Tourette's syndrome
Authors: Lang Anthony E. , Consky Earl , Sandor Paul
Published: January 2005

We describse the case of a young woman with Tourette's syndrome who incorporated sign language into her tic behavior. Sign language was used in complex “phonictic” such as swearing, echoing what others said, or repeating what she said, read, or thought. We suggest the descriptive terms “coprolaliopraxia,” “echolaliopraxia,” and “palilaliopraxia” to denote these symptoms. The incorporation of such complex, learned movements into the repertoire of hyperkinesias further emphasizes the complicated association between purposeful and automatic execution of movements comprising tic behavior. This case also provides strong evidence against the suggestion that obscenities vocalized in Tourette's syndrome are due to a random generation of high‐probability sequences of letters or phonemes.
Risk factors for late‐ onset Alzheimer's disease: A population‐ based, case‐control study
Authors: Fratiglioni Laura , Ahlbom Anders , Viitanen Matti , Winblad Bengt
Published: January 2005

Our current Knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early‐onset disease. This study aimed to determine the risk factors for late‐onset Alzheimer's disease using a case‐control approach. Ninetyeight case and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2;95% confidence interval, 1‐8‐5.7) with the presence of at least one first‐degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4–13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our date suggest the the main risk factor for late‐onser alzheimer's disease is a family history of dementia, as has been previously reported for early‐onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this from of the disease.
Increased mitochondrial DNA in blood vessels and ragged‐red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS)
Authors: Tokunaga Makoto , Mita Shuji , Sakuta Ryoichi , Nonaka Ikuya , Araki Shukuro
Published: January 2005

Using in situ hybridization, we studied muscle hiopsy specimens from 4 patients with mitochondrial myoparthy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Three of the 4 prients with MELAS had a mutation at position 3243 of mitochondrial DNA (mt DNA) in the transfer RNA leu(UUR) gene, and the other patient had a mutation at position 3271 in the same transfer RNA leu(UUR)gene. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) ware extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase‐reactive blood vessels) and ragged‐red fibers. Cytochrome oxidase activity in most of these reactive blood vessels and ragged‐red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome c oxidase is not a primarily defective enzyme. The pattern of expression of genes of mtDNA‐encoded ribosomal RNA and the protein coding region cytochrome c oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.
Ocular torsion and tilt of subjective visual vertical are sensitive brainstem signs
Authors: Dieterich Marianne , Brandt Thomas
Published: January 2005

Deviations of the position of the ey in the roll plance, ocular trosion (OT), and the subjective visual vertical (SVV) wre systematically studied in 111 patients with acure vascular brainstem lesions. Of the 111 partents, 104 (94%) showed a direction‐specific pathological tilt of the static SVV in our series, Sevenry‐one (83%) of 86 partients exhibited pathological static OT of one (47%) or both (36%) eyes. OT and SVV tilts are therefore sensitive signs in acture unilateral brainstem disorders. Measurements of SVV and OT may prove to be useful components of the neuroophthalmological evaluation. With respect to the directions of pathological tilt, SVV an OT are generally in the same direction. Based on neuroimaging, we conclude that all unilateral brainstem lesion caudal to the upper pons cause ipsiversive Ot of one or both eyes, with concurrent ipsiversive tilts of SVV adjustments; all lesions rostral to this pontine level cause Contraversive tills of OT and SVV. Evidence is presented that pathological tilts of OT and SVV are secondary to a dysfunction of the tonic bilateral vestibular imputs that stabilize the eyes and head in normal upright position in the roll plance and dominate our perception of verticality.
Loss of C1 and C3 epinephrine‐synthesizing neurons in the medulla oblongata in parkinson's disease
Authors: Gai W.‐P. , Geffen L. B. , Denoroy L. , Blessing W. W.
Published: January 2005

We used immunohistochemical analysis to determine whether medulla oblongata neurons containing phenylethanolamine N‐methyltransferase (PNMT) are affected in patients who died with idiopathic Parkinson's disease (n = 7) compared with age‐matched control subjects who died with nonneurological diseases (n = 8). Transverse sections (50μm) of medulla were prepared either for conventional neuropathological examination or for the immunohistochemical demonstration of PNMT. Immunopositive neurons at approximately 30 rostrocaudal levels, evenly spaced throughout the whole medulla, were mapped and cells in each section were counted with a camera lucida system linked to a computer. In the ventrolateral medulla, from the level of the obex to 11 mm rostral to the obex where the C1 group of neurons is located, there were 7,631 ± 844 PNMT‐positive neurons in control brains and 3,604 ± 1,051 in brains affected by Parkinson's disease (47% of control). Many PNMT‐positive neurons contained Lewy bodies. We observed a previously undescribed midline (C3) group of PNMT‐positive neurons in normal brains, and this group was also severely affected (12% of control) in parkinsonian brains. Neither the C2 group nor the small PNMT‐positive neurons in the nucleus tractus solitarii were significantly reduced in numbers but there was a reduction in the numbers of melanin‐pigmented cells in both the ventrolateral (50% of control) and the dorsomedial (79% of control) region. Our results demonstrate a selective loss of C1 and C3 PNMT‐positive neurons, providing the first quantitative evidence for damage to these presumed brainstem sympathetic premotor neurons in Parkinson's disease. These changes may underlie some of the autonomic symptoms occurring in this condition.