bluuebunny/crossref_metadata_2025 huggingface dataset:
Adoptive transfer of murine relapsing experimental allergic encephalomyelitis
Authors: Lublin Fred D.
Published: January 2005

Relapsing experimental allergic encephalomyelitis (EAE), an autoimmune disorder resembling multiple sclerosis, has been produced by inoculating SJL/J mice with spinal cord or myelin basic protein in appropriate adjuvants. To determine whether initially sensitized lymphocytes or the persistence of antigen depots in the animal were responsible for the relapsing episodes of inflammatory demyelination, adoptive transfer studies were undertaken utilizing lymphocytes from relapsing EAE‐immunized donors transferred directly or after in vitro culture. In direct‐transfer studies donor lymphocytes produced clinical and pathological signs of relapsing EAE in 3 of 7 recipients of lymph node lymphocytes and 1 of 5 recipients of splenic lymphocytes. In vitro culture of lymphocytes in myelin basic protein or T cell growth factor prior to transfer increased both the incidence of disease and the number of animals having relapses, and allowed transfer with fewer lymphocytes. Because all animals had delayed onset of disease, this study demonstrates that the ability to develop relapsing inflammatory demyelination is transferable with lymphocytes and does no require the presence of antigen.
Maternally inherited mitochondrial myopathy and myoclonic epilepsy
Authors: Rosing Howard S. , Hopkins Linton C. , Wallace Douglas C. , Epstein Charles M. , Weidenheim Karen
Published: January 2005

A family is described with familial myoclonic epilepsy associated with mitochondrial myopathy. The disorder follows a maternal inheritance pattern consistent with a mitochondrial DNA (mtDNA) mutation. The large kindred permitted exclusion of autosomal dominant, recessive, and X‐linked patterns of transmission. Several characteristics of the inheriatnce and variability of expression within the pedigree are consistent with recently acquired knowledge about the genetics of human mtDNA. The clilnical spectrum of disease is compatible with a proportionality model of mutant and wild‐type mt DNAs.

Muscle biopsies of affected patients showed an increased number of abnormal muscle mitochondria. Serum levels of pyruvate or and lactate were elevated. The most severely affected pateint had constant myoclonic jerking, dementia, ataxia, spasticity, hearing loss, and hopoventilation. Cerebral dysfuntion in patients with mild involvement waas marked by prominent photic driving seen on electroencephalograms and high‐amplitude visual and somatosensory evoked responses but no myoclonus, ataxia, or dementia. The individual clinical features of the disease worsen over time for all patients; however, mildly affected patients have not become moderately afftected and moderately affected patients have not become severely affected.
Alzheimer changes in nondemented patients younger than sixty‐five: Possible early stages of Alzheimer's disease and senile dementia of Alzheimer type
Authors: Ulrich J.
Published: January 2005

Senile plaques (SP) and neurofibrillary tangles (NFT) were found in 38 (74.5%) of 51 unselected brains of nondemented patients who died between the ages of 55 and 64 years. A high proportion (22, or 43%) had only NFTs. These were consistently present in the entorhinal cortex and/or the hippocampus; the olfactory bulb, the amygdala, and the nucleus basalis of Meynert were also occasionally invloved. Isolated SPs were seen in only 3 brains (6%); SPs and NFTs coexisted in 13 (25.5%). The distribution patterns of NFTs and SPs occurred in a more generalized distribution over the base and convexity of the cerebrum. The plaques were usually small (30 μ in diameter) and consisted of delicate fibrillary material. Other types of SP were also seen. The incidence of various types of plaques in nondemented patients is considered to indicate a morphological evolution of these structures.
Tropical spastic paraparesis: A neuroepidemiological study in Colombia
Authors: Román Gustavo C. , Román Lydia N. , Spencer Peter S. , Schoenberg Bruce S.
Published: January 2005

A geographic isolate of tropical spastic paraparesis (TSP) in Tumaco, Colombia, is described. Fifity confirmed cases were identified (29 men, 21 women) with an estimated prevalence rario of 98 cases per 100, 000 population. Patients with identified cases ranged in age from 24 to75 years (mean, 46.5). TSP begins with burning feet, leg stiffness, spastic bladder, and, in men, impotence. Patients exhibited leg weakness, spasticity, hyperreflexia, and scissoring gait. Babinski, Chaddock, and Hoffmann signs could elicited. Ankle reflexes and vibratory sensation of the feet were decresed. Intellectual function, coordination, and cranial nerves remained normal. TSP is slowly progressive disorder but so far there have been no deaths from it. Forth cases in this report began between 1971 and 1980; the earliest documented case began in 1952. Living conditions and occupations of the patients were typical for the region. Yaws had occured in 74% of confirmed cases. No likely etiological neurotoxix or nutritional factors identified. TSP aslo has been described in India, Africa, the Seychelles, and Jamaica.
Seizures and cerebral infarction in the full‐term newborn
Authors: Levy Susan R. , Abroms Israel F. , Marshall Paul C. , Rosquete Elizabeth E.
Published: January 2005

Cerebral arterial infarction is a more common cause of neonatal seizures than has previously appreciated. In 50 full‐term newborns with seizures studied, 7 had cerebral infaction which was the secondmost common definable cause of seizures. We describe these 7 ful‐term infants with cerebrovascular accidents who presented with focal or generalized seizures. Onstetrical histories were normal in 5 of these patients. Their neurological examinations demonstrated lethargy and generalized hypotania. Electroencephalograms demonstrated focal abnormalities in 4 infants. Computed tomographic scans in the first week of life showed infarction in 6 newborns and in another at age 6 months. Neonatal stroke should be considered as a cause of seizures in a full‐term newborn in spite of a normal obstetrical history and a nonfocal neurological examination.
Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy
Authors: Graham Anna R. , Johnson Peter C.
Published: January 2005

Direct immunofluorescence examination was performed on peripheral nerve from 16 patients with diabetes mellitus and 53 additional patients with peripheral neuropathy of diverse cause. Six nerves from patients with diabetes mellitus yielded positive findings: 4 had grandular and lamellar deposition of IgM within the perineurium (of which 2 also had fibrinogen, IgA, C3, and albumin and I also had IgG); 1 had IgM, C3, and C4, and perineurial fibrinogen; the sixth contained linear perineurial C3 and fibrinogen. These 6 nerves contained axonal degeneration (3), axonal degeneraion with chornic demyelination (1), microvasculitis with wallerian degeneration (1), and no pathological change (1). Sixteen of 53 nerves from nondiabetics yielded positive findings with immunofluorescence, possibly as a result of vascular leakage or as a manifestation of impaired removal of plasma proteins. The deposition of immunoreactants, as well as other plasma proteins, in peripharal nerve from patients with diabetes mellitus probably represents a “trapping” phenomenon reflecting altered basement membrane permeability. Alternatively, the changes could reflect a defect in the blood‐nerve barrier in diabetic microangiopathy.
Postoperative contrast enhancement in patients with brain tumor
Authors: Caincross J. Gregory , Pexman J. H. Warwick , Rathbone Michel P. , DelMaestro Ronaldo F.
Published: January 2005

Contrast enhancement resulting from surgical trauma may mimic residual enhancing tumour, thereby complicating the interpretation of postoperative computed tomographic scans. We assessed the natural history of postoperative enhancement in 10 patients with brain tumour. Contrast enhancement distinguishable from residual enhancing tumor appered along the operative margin followingtumor resections but not lobectomies. Enhancement appeared as early as the fifth postoperative day, was most intense at two weeks, and persisted for several months. Prior to the fifth postoperative day, enhancement reflected residual tumor. Edema and artifacts were more prominent on the first and second postoperativedays than on the third and fourth. We recommend that postoperaive computed tomographic scans to assess residual enhancing tumor be performed on the third or fourth postoperative day. This timing avoids postoperative enhancement and minimizes interpretative difficulties caused by artifacts.
Leptomeningeal dissemination of primary central nervous system tumors of childhood
Authors: Packer Roger J. , Siegel Kathy R. , Sutton Leslie N. , Litmann Phillip , Bruce Derek A. , Schut Luis
Published: January 2005

Presymptomatic craniospinal radiation therapy improves the rate of survival for children with brain tumors, which frequently metastasize to the leptomeninges. Radiotherapy may cause neurological damage and should be used only in patients considered to be at highest risk for leptomeningeal dissemination (LMS) at either the time of initial diagnosis or onset of disease relapse. We reviewed 314 consecutive patients with brain tumors to determine the incidence, timing, and importance of LMS. LMS occurred in 60 (19%) children. LMS occurred before diagnosis in 30 patients, as the only site of relapse or simultaneously with local first disease recurrence in 17 patients, and after local disease recurrence in 13 patients. Children with primitive neuroectodermal tumors, anaplastic gliomas, and ependymomas most frequently had LMS. Patients with primitive neuroectodermal tumors and posterior fossa anaplastic gliomas frequently had LMS before diagnosis or at the onset of relapse, whereas patients with ependymomas had LMS after local disease relapse. Both myelography and cerebrospinal fluid cytological examination are required to diagnose LMS.
Complex partial status epilepticus: A depth‐electrode study
Authors: Williamson Peter D. , Spencer Dennis D. , Spencer Susan S. , Novelly Robert A. , Mattson Richard H.
Published: January 2005

Of 87 patients with complex partial epilepsy who were evaluated with depth electrodes, 8 developed complex partial status epilepticus (CPSE). Seizures originated extratemporally in all 8 patients. Frontal lobe onset was established in 4 patients and was probable in 1 more. Medial parietal onset was documented in 1 patient. Medial occipitoparietal onset occurred in another, and 1 patient had multifocal onsets. Even when seizures did not begin frontrally, the frontal lobes were prominently involved during CPSE. CPSE did not occur in 60 patients with seizures originating in the temporal lobe. Both recurrent clinical seizures and continuous altered behavior were observed. Some patients exhibited both clinical patterns at different times during the same episode. Depth recording consistently demonstrated recurrent isolated seizure discharges throughout episodes. The clinical patterns were related, in part, to electroencephalographic seizure frequency, duration, and intensity. Episodes of CPSE were not associated with intellectual deterioration.
Vitamin E deficiency associated with vision loss and bulbar weakness
Authors: Larsen Paul D. , Mock Donald M. , O'Connor Patrick S.
Published: January 2005

We describe a 14‐year‐old boy who was severely debilitated by the neurological syndrome associated with vitamin E deficiency secondary to chronic cholestatic liver disease. In addition to the usual neurological deficits described with this deficiency, the patient had severe bulbar weakness and vision loss which we attribute to the degree and duration of his vitamin E deficiency. Vitamin A deficiency may have contributed to his visual disturbance. Early recognition of vitamin E deficiency is important, as the neurological and visual disorders which result are treatable.
Intravenous lisuride corrects oscillations of motor performance in Parkinson's disease
Authors: Obeso J. A. , Luquin M. R. , Martínez Lage J. M.
Published: January 2005

Seventeen lisuride infusions were given to 12 patients with Parkinson's disease who showed daily oscillations in motor performance. The mean lisuride dose given in continuous intravenous infusion was 0.59 mg (range, 0.3 to 1.0 mg) during a mean period of 9.0 hours (range, 5 to 12 hours). A significant reduction in the number of hours “off” was obtained in all patients. Additional oral levodopa was necessary to maintain normal mobility throughout the infusions. Severe hypotension occurred in 2 patients which required termination of the infusions. Five patients experienced nausea, sweating, and malaise but this did not necessitate interruption of the infusions. Lisuride appears to be one of the best available dopamine agonists for continuous dopaminergic stimulation.
Cerebral mapping of apraxia in Alzheimer's disease by positron emission tomography
Authors: Foster Norman L. , Chase Thomas N. , Patronas Nicholas J. , Gillespie Marjorie M. , Fedio Paul
Published: January 2005

The ability to mimic skilled movements or to pantomime them in response to spoken command was compared with psychometric performance and with regional glucose utilization as estimated by [18F]fluorodeoxyglucose positron emission tomography in 17 right‐handed patients with Alzheimer's disease and 6 age‐matched normal subjects. Apraxia scores, both on tests to command and to imitation, were significantly lower in the Alzheimer patients. Imitation scores correlated best with performance on tests of visual–spatial ability and with cortical metabolism in the right parietal lobe; command scores related most closely with the results of tests reflecting verbal proficiency and with cortical metabolism in the left inferior hemisphere, especially frontally. Apraxia to command and imitation may thus reflect neuronal dysfunction in distinct cerebral regions in patients with Alzheimer's disease.
Granule cell deficit in the mouse cerebellum after total asphyxia
Authors: Yoshioka Hiroshi , Yoshida Akira , Ochi Masaharu , Iino Shigeru , Fujiwara Katsuhiko , Ishimura Kazuhisa , Kusunoki Tomoichi
Published: January 2005

The cerebellar granule cell continues to proliferate after birth in the mouse as well as in the human being. Total asphyxia in the neonatal period in 40 mice resulted in a 13% reduction in the granule cell number and a 7% reduction in the Purkinje cell number. Differential effects on granule cell and Purkinje cell populations were noted when particular cerebellar lobules were examined.
Kernicterus in an adult
Authors: Waser Marco , Kleihues Paul , Frick Paul
Published: January 2005

A 43‐year‐old woman was initially seen because of icterus. Clinical investigations revealed severe hepatic damage probably due to non‐A, non‐B hepatitis. She was treated with extracorporeal charcoal‐column perfusion but died two weeks later in a hepatic coma. At autopsy, the brain showed kernicterus with typical discoloration of the hippocampus, the subthalamic nuclei, and the cerebellar dentate nuclei. Kernicterus in an adult is very rare. In this case, extracorporeal charcoalcolumn perfusion treatment led repeatedly to severe depletion of fibrinogen, with extensive hemorrhages. Overload of the already reduced hepative glucuronyl‐transferase capacity resulted in high serum levels of unconjugated bilirubin, an apparent prerequisite for the development of bilirubin encephalopathy.
Carotid surgery, cognitive function, and cerebral blood flow in patients with transient ischemic attacks
Authors: Hemmingsen Ralf , Mejsholm Birgitte , Vorstrup Sissel , Lester Jack , Engell Hans Christian , Boysen Gudrun
Published: January 2005

Psychological testing, cerebral blood flow (CBF) measurement, and computed tomographic scan were performed before and 3 months after operation in 31 patients subjected to endarterectomy of the internal carotid artery (ICA) because of transient ischemic attacks and in 11 control patients operated on for atherosclerosis of the lower extremities. In preoperative psychological testing both carotid surgery patients and controls performed somewhat below the normal level for their age group. Postoperatively, cognitive functions improved in the carotid surgery group but not in the control group. The improvement was related to the laterality of the operation, being more marked in verbal tests in patients with left ICA operation and in visuospatial tests in patients with right ICA operation. Postoperatively regional CBF improved in 2 patients only. Hence the intellectual improvement could not be related to changes in CBF. Intellectual deterioration in patients with internal carotid atherosclerosis may be delayed or terminated by surgical abolition of the source of multiple cerebral embolizations.
Cerebral metabolic effects of neonatal seizures measured with in vivo 31P NMR spectroscopy
Authors: Younkin Donald P. , Delivoria‐Papadopoulos Maria , Maris John , Donlon Eileen , Clancy Robert , Chance Britton
Published: January 2005

In vivo phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy was used to evaluate changes in cerebral high‐energy phosphate compounds in 8 infants with seizures. During the study 4 babies had seizures that caused a 50% decrease in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio. Focal seizures caused lateralized decreases in the PCr/Pi ratio; generalized seizures caused bilateral decreases. Postictal spectra had increased PCr/Pi ratios, presumably due to postictal inhibition. Interictal 31P NMR spectra were normal. One patient's seizures were successfully treated with intravenously administered phenobarbital during NMR data acquisition, causing an immediate increase in the PCr/Pi ratio from 0.7 to 1.2. These studies indicate that cerebral PCr concentration decreases by approximately 33% and that oxidative metabolism increases by approximately 45% during neonatal seizures. Five babies had PCr/Pi ratios of less than 0.8 during seizures and subsequently developed long‐term neurological sequelae, which suggests that neonatal seizures may cause or exacerbate cerebral injury by increasing cerebral metabolic demands above energy supply.
Developmental Foix‐Chavany‐Marie syndrome in identical twins
Authors: Graff‐Radford Neill R. , Bosch E. Peter , Stears John C. , Tranel Daniel
Published: January 2005

Foix, Chavany, and Marie described a syndrome of faciopharyngoglossomasticatory diplegia resulting from bilateral anterior opercular infarction. We describe identical twins who have a developmental form of the syndrome. The twins, aged 41 years, were the product of a normal pregnancy and birth, but had subsequent delayed motor milestones, seizures, poor language development, mild mental retardation, drooling, absent gag reflexes, inability to protrude the tongue, briskk jaw jerks, impaired fine finger movements, symmetrical brisk reflexes, flexor plantar responses, and mildly spastic gait. Magnetic resonance imaging showed bilateral perisylvian cortical dysplasia compatible with polymicrogyria and incomplete opercula formation.
Loss of pedunculopontine neurons in progressive supranuclear palsy
Authors: Zweig Richard M. , Whitehouse Peter J. , Casanova Manuel F. , Walker Lary C. , Januarykel William R. , Price Donald L.
Published: January 2005

In the present study, the number of neurons (>20 μm in diameter) within the lateral part of the pedunculopontine nucleus pars compacta (PPNc) was determined at six rostrocaudal levels in 3 subjects with progressive supranuclear palsy (PSP), in 9 subjects with Alzheimer's disease, and in 6 age‐matched control subjects. At each level examined, significantly fewer neurons were present in patients with PSP than in control subjects (49 to 69% reduction). Significant differences in numbers of neurons were not demonstrated between control subjects and patients with Alzheimer's disease. The extent of pathological changes, particularly neurofibrillary tangles, was examined within the PPNc of subjects in these three groups. The average number of neurofibrillary tangles in a 12‐μm‐thick midlevel section of the lateral PPNc was 68.7 in subjects with PSP, 18.3 in those with Alzheimer's disease, and 3.0 in aged control subjects. These abnormalities of PPNc neurons in PSP may play important roles in some of the clinical features characteristic of this disease.
Familial alzheimer's disease in american descendants of the volga germans: Probable genetic founder effect
Authors: Bird Thomas D. , Lampe Thomas H. , Nemens Ellen J. , Miner Gary W. , Sumi S. M. , Schellenberg Gerard D.
Published: January 2005

Five families are described in which autopsy‐confirmed presenile Alzheimer's disease (AD) has occurred in men and women over multiple generations consistent with autosomal dominant inheritance. All 5 families are descendants of a group of immigrants known as the Volga Germans who came to the United States between 1870 and 1920. Their ancestors moved from Germany to the southern Volga region of Russia in the 1760s. All 5 American families are descendants of persons originally living in two small adjacent Volga German villages and share several surnames known to have been present in the census records of those villages. Although a single affected common ancestor cannot be identified, it is likely that the AD in these families represents an autosomal dominant gene inherited from one ancestor (the founder effect). This information is of importance in the genetic study of AD in these families because it greatly increases the probability of genetic homogeneity. There are more than 300,000 American descendants of the Volga Germans, and the prevalence of AD has never been studies in this population.
Neurological complications of human immunodeficiency virus infection in patients with lymphadenopathy syndrome
Authors: Janssen Robert S. , Saykin Andrew J. , Kaplan Jonathan E. , Spira Thomas J. , Pinsky Paul F. , Sprehn Gwen C. , Hoffman James C. , Mayer W. Brem , Schonberger Lawrence B.
Published: January 2005

To determine if there is a relationship between neurological abnormalities and human immunodeficiency virus (HIV) infection in patients with lymphadenopathy syndrome (LAS), we studied 39 homosexual/bisexual men with LAS (mean duration of LAS, 4.1 years) and 38 homosexual/bisexual men who were seronegative for HIV (controls). Six LAS patients had histories of symptoms suggesting mononeuropathy, 9 had symptoms suggesting distal symmetrical polyneuropathy, and 9 had histories of herpes zoster radiculitis. Overall, significantly more LAS patients (18) than controls (3) had histories of symptoms or signs of neurological abnormality (odds ratio, 10.0; p = 0.0003). By neuropsychological assessment, 9 of 18 LAS patients and 2 of 26 controls were abnormal (odds ratio, 12.0; p = 0.004). Of those abnormal on the neuropsychological assessment, the majority scored in the mildly impaired range. Magnetic resonance imaging was abnormal in 1 LAS patient and in 1 control. Neither neurological nor neuropsychological abnormalities correlated with duration of LAS, absolute T‐helper lymphocyte count, or T‐helper/T‐suppressor lymphocyte ratio. These results indicate an association of neurological and neuropsychological abnormalities with HIV in patients with LAS. They suggest that mild neurological abnormalities in LAS are common and that HIV may directly or indirectly be the cause.
Phenytoin does not block hippocampal long‐term potentiation or frequency potentiation
Authors: Stringer Janet L. , Lothman Eric W.
Published: January 2005

Recently, a theoretical scheme offered mechanisms by which phenytoin exerts its antiepileptic effects. Two predictions arising from this proposal are that phenytoin would suppress alterations in the potency of excitatory neurotransmission engendered by repetitive neural activation and that this effect would be augmented by displacing the extracellular concentration of K+ ([K+]0) away from its normal resting level. In the present study, we tested these predictions by examining the effects of phenytoin on short‐ and long‐term functional plasticity in vitro in the hippocampus. Extracellular field potentials were recorded in the CA1 region of the rat hippocampal slice in response to stimulation of the Schaeffer collaterals. Phenytoin (20 μg/ml) did not affect baseline excitatory neurotransmission as measured by input‐output curves (population spike amplitude versus stimulus intensity) obtained at low stimulus rates. The drug also had no effect on either frequency potentiation (2.5 Hz) or long‐term potentiation (50 Hz, 500 msec; or 400 Hz, 20 msec). When [K+]0 was raised to levels seen during seizures, the drug still did not alter frequency potentiation or long‐term potentiation induced by either type of stimulus train. Phenytoin also had no effect on either stimulus‐locked or spontaneous epileptiform bursts that appear in conjunction with elevated [K+]0 or on stimulus‐locked bursts that appear in the presence of 0.75 mM extracellular calcium. These results, showing that certain forms of functional synaptic plasticity are not affected by phenytoin, suggest a means by which phenytoin could exert its antiepileptic action without interfering with normal brain function.
Cerebrospinal fluid IgG in childhood: The establishment of reference values
Authors: Rust Robert S. , Dodson W. Edwin , Trotter John L.
Published: January 2005

A retrospective analysis of quantitative and qualitative immunoglobulin G (IgG) results from 253 children who were either medically and neurologically normal or highly unlikely to have abnormalities of CSF IgG is reported. Normal values in this reference population vary with age for CSF/albumin IgG ratio and CSF/serum IgG index and are significantly different from the adult reference values. The rate of false positivity is lower for quantitative values than for qualitative IgG determinations (oligoclonal bands).
Differential cognitive impairment in alzheimer's disease and huntington's disease
Authors: Brandt Jason , Folstein Susan E. , Folstein Marshal F.
Published: January 2005

The differentiation between cortical and subcortical dementias requires that the cognitive characteristics of dementias attributable to different causes be discriminable. For large samples of Alzheimer's disease and Huntington's disease patients, distinct cognitive profiles were obtained on the Mini‐Mental State Exam. The profile differences were independent of severity of dementia and were sufficiently robust to classify patients as Alzheimer's disease or Huntington's disease with 84% accuracy. The qualitative differences in cognitive functioning may also be typical of other cortical and subcortical dementias.
Long‐term duodenal infusion of levodopa for motor fluctuations in parkinsonism
Authors: Sage J. I. , Trooskin S. , Sonsalla P. K. , Heikkila R. , Duvoisin R. C.
Published: January 2005

We report the long‐term clinical responses of 2 parkinsonian patients with severe “on‐off” phenomena who have been receiving continuous duodenal levodopa (LD) infusions. The rate of LD infusion needed to keep the patients just “on” Decemberlined gradually during the initial 60 days of infusion and then remained constant. Total LD intake Decemberlined rapidly during the first several days and gradually for another 60 days, after which it remained stable. Motor fluctuations virtually disappeared in both patients during the time of the day when the pump was in use. This was accompanied by a Decemberline in the plasma LD concentration needed to just maintain the “on” stage in one patient.
Eales' disease presenting as stroke in the young adult
Authors: Gordon Marchk Forrest , Coyle P. K. , Golub Barry
Published: January 2005

Eales' disease is an uncommon idiopathic disorder characterized by retinal perivasculitis and recurrent vitreous hemorrhages in young males. Associated neurological involvement is rare. We report a 38‐year‐old man who presented with stroke attributed to Eales' disease.
Nondextrality and autoimmune disorders among relaives of language‐disabled boys
Authors: Urion David K.
Published: January 2005

The incidences of autoimmune diseases, nonright‐handedness, and premature graying of the hair have been said to be increased among the relatives of dyslexic persons. I undertook a prospective evaluation of the relatives of 100 language‐disabled boys seen in a tertiary hospital learning disabilities clinic. I established the incidence of these characteristics and compared the results with those obtained from the relatives of 100 boys referred to a neurology clinic for evaluation of seizures or muscle disease. The families of the language‐disabled boys were divisible into two groups, one with an increased incidence of these characteristics and one with a Decemberreased incidence as compared with the control group. This suggests a biological heterogeneity among these families, despite a similar phenotype among all the language‐disabled probands.
Hallervorden‐spatz syndrome: Clinical and magnetic resonance imaging correlations
Authors: Sethi K. D. , Adams R. J. , Loring D. W. , El Gammal T.
Published: January 2005

Two women with a presumptive diagnosis of Hallervor‐den‐Spatz syndrome had a combination of dystonia and parkinsonism. One had retinitis pigmentosa. Neuropsychological testing revealed Decemberreased verbal fluency and visuoconstructional and motor deficits. Magnetic resonance imaging performed with a high‐field‐strength unit (1.5 Tesla) showed striking abnormalities in the globus pallidus bilaterally (“eye‐of‐the‐tiger” sign). Magnetic resonance imaging may prove useful in the diagnosis of Hallervorden‐Spatz syndrome.
Depth electrode investigations in patients with bitemporal epileptiform abnormalities
Authors: So Norman , Gloor Pierre , Quesney L. Felipe , Jones‐Gotman Marilyn , Olivier André , Andermann Frederick
Published: January 2005

Fifty‐seven patients showing bitemporal independent epileptiform abnormalities on extracranial electroencephalograms (EEGs) in whom the epileptogenic zone could not be localized or lateralized by extracranial EEG and other noninvasive tests were investigated with stereotactic depth electrode recordings. In a majority of 44 patients (77%), seizures originated exclusively or with a strong predominance in one temporal lobe only. Of the remaining 13 patients (23%), 8 had seizures originating independently in either temporal lobe without significant lateralized predominance, and 5 had multiple seizure patterns, which were often diffuse. The patterns of seizure onset as recorded by depth electrodes tended to vary even in the same patient. Electrical stimulation studies and the determination of afterdischarge thresholds were of limited utility for lateralization of seizure onset.
Sleep abnormalities in progressive supranuclear palsy
Authors: Aldrich Michael S. , Foster Norman L. , White Roberta F. , Bluemlein Laurie , Ba Gregory Prokopowicz
Published: January 2005

We studied sleep patterns for three nights in 10 subjects with moderate to severe progressive supranuclear palsy and correlated the findings with disease severity using quantitative measures of motor, cognitive, and eye movement impairment. All subjects had severe insomnia, spending 2 to 6 hours awake per night; the mean time awake per night for the group was more than 4 hours. Sleep latency became shorter and the number of awakenings increased with greater motor impairment, and total sleep time declined as dementia worsened. These findings indicate that in progressive supranuclear palsy insomnia is related to disease severity. Insomnia associated with progressive supranuclear palsy appears to be worse than the insomnia of Parkinson's disease or Alzheimer's disease and may be due to degenerative changes in brain structures responsible for sleep maintenance.
The effect of MK‐801 on kindled seizures: Implications for use and limitations as an antiepileptic drug
Authors: Williamson John M. , Lothman Eric W.
Published: January 2005

MK‐801 is a new drug that produces a noncompetitive blockade at the subclass of glutamate receptors activated by N‐methyl‐D‐asparate (NMDA). The antiepileptic properties of MK‐801 were studied using kindled seizures as a model of complex partial seizures with secondary generalization. A test protocol was employed that allowed: (1) examination of the efficacy of MK‐801 against several parameters that gauge different aspects of epiletogenesis; (2) determination of the time‐action profile of these effects; and (3) examination of the toxicity of MK‐801 in animals experiencing seizures. The drug was found to be potent against the spread of seizures but less effective against parameters linked to partial seizures. At the higher doses of the drug required to truncate hippocampal afterdischarges, considerable neurotoxicity was encountered. In addition, the antiepileptic effects of MK‐801 showed a use dependence so that, at a given time after the drug was administered, a greater suppression of seizures was noted if there had been preceding seizures in the presence of the drug than if there had not been. These findings indicate that there may be limitations to the clinical utility of MK‐801 as an antiepileptic agent and that the drug may provide greatest benefit when used for the suppression of seizure generalization and when seizures are closely spaced.
Do oligodendrocytes mediate iron regulation in the human brain?
Authors: Gerber Megan R. , Connor James R.
Published: January 2005

We used immunohistochemical studies to demonstrate that transferrin (the iron mobilization protein) and ferritin (the iron storage protein) are specifically localized in oligodendrocytes in gray and white matter of the human central nervous system. In addition, iron is also localized predominantly in oligodendrocytes. Oligodendrocytes have been well established as the cells responsible for myelin production in the central nervous system. The results of this study suggest that oligodendrocytes (or a subpopulation of oligodendrocytes) might have the additional function of mediating iron mobilization and storage in the central nervous system.
Abnormal pattern electroretinograms in patients with senile dementia of the alzheimer type
Authors: Trick Gary L , Barris Michael C , Bickler‐Bluth Michelle
Published: January 2005

Patients with senile dementia of the Alzheimer type frequently have difficulty performing visual tasks. These difficulties may be due, at least partially, to degenerative changes in both the primary visual pathway and the visual association areas. To determine whether retinal ganglion cell dysfunction contributes to visual loss in senile dementia of the Alzheimer type, we tested a group of patients with this disease (n = 13) using the patten‐reversal electroretinogram to both low (4.0 reversals per second) and high (16.0 reversals per second) temporal frequency checkerboard patterns (1.0 degree checks). Significant amplitude reduction were noted for the patients relative to age‐matched control subjects (n = 30). In addition, the observed amplitude reduction were most pronounced for the high temporal frequency condition. Therefore, the results are consistent with retinal ganglion cell dysfunction and support the notion that optic nerve damage induced by senile dementia of the Alzheimer type preferentially affects the larger, faster‐conduction retinal ganglion cells along with their retinocortical projections.
Acetaminophen metabolism by cytochrome P450 monooxygenases in Parkinson's disease
Authors: Factor Stewart A. , Weiner William J. , Hefti Franz
Published: January 2005

It has been suggested that alterations in the activity of cytochrome P450 monooxygenases may play a role in the pathogenesis of Parkinson's disease, particularly in patients who had onset before the age of 40. We studied the P450‐mediated metabolism of acetaminophen to 3‐hydroxy‐acetaminophen in 26 patients with Parkinson's disease and in 18 control subjects. After subjects ingested 1,000 mg acetaminophen, urine was collected under controlled conditions. Acetaminophen and 3‐hydroxy‐acetaminophen were measured in the urine using newly developed high‐pressure liquid chromatography methods. The ratio of 3‐hydroxy‐acetaminophen to acetaminophen was calculated for each patient and no significant differences were observed in patients compared with control subjects. Abnormal metabolism was not observed in patients who had onset of Parkinson's diseae at or before the age of 40. In addition, no difference in metabolic activity was observed between the patients who were treated with levodopa/carbidopa and those who were not treated. These findings suggest that there are no alterations of P450‐mediated metabolism of acetaminophen in patients with Parkinson's disease.
Sympathetic skin responses are decreased and lymphocyte beta‐adrenergic receptors are increased in progressive multiple sclerosis
Authors: Karaszewski Joseph W. , Reder Anthony T. , Maselli Ricardo , Brown Margaret , Arnason Barry G. W.
Published: January 2005

Immune abnormalities, including deficient CD8 lymphocyte‐mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of betaadrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic‐mediated response. The density of beta‐adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 ± 1.8 fmol/106 cells in control subjects and 18.7 ± 2.6 fmol/106 cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 ± 0.4 fmol/106 cells in control subjects and 9.1 ± 1.6 fmol/106 cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 ± 0.1 fmol/106 cells in control subjects and 1.8 ± 0.4 fmol/106 cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10−5 M (–)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta‐adrenergic receptor density found on CD8 lymphocytes may be related.
Posthypoxic glucose supplement reduces hypoxic‐ischemic brain damage in the neonatal rat
Authors: Hattori Haruo , Wasterlain Claude G.
Published: January 2005

We evaluated the effect of posthypoxic glucose supplement in a neonatal hypoxic‐ischemic animal model. Seven‐day‐old rats underwent bilateral ligation of the carotid arteries, followed by exposure to an 8% oxygen atmosphere for 1 hour. The extent of hypoxic‐ischemic brain damage was assessed histologically 72 hours later. Gulcose load immediately after the end of the hypoxic exposure reduced the volume of neocortical infarction to 37% of the unsupplemented value, and attenuated ischemic damage in the striatum and the dentate gyrus. At the end of the hypoxic exposure, the brain level of glucose was 0.3 mmol/kg and the level of lactate, 9 mmol/kg. Glucose supplement produced a rapid rise in brain glucose level to 3 to 5 mmol/kg over the next 2 hours. Lactate in both brain and plasma gradually fell toward the baseline level during the first hour of recovery. Posthypoxic glucose supplement slightly retarded lactate restitution. At any period of this neonatal model, brain lactate levels did not exceed the toxic level, which is postulated to be responsible for cerebral infarction in adult ischemic models. These results illustrate the important role of glucose in the development of neonatal hypoxic‐ischemic encephalopathy and the fact that full cortical infarction can develop even if brain lactate levels are low.
NMDA antagonists potentiate antiparkinsonian actions of L‐dopa in monoamine‐depleted rats
Authors: Klockgether Thomas , Turski Lechoslaw
Published: January 2005

Systemically administered N‐methyl‐D‐aspartate (NMDA) antagonists, MK‐801((+)5‐methyl‐10,11‐dihydro‐5H‐dibenzo(a, d)cyclohepten‐5,10‐imine maleate) and CPP(3‐[(±)‐2‐carboxypiperazin‐4‐y1]‐propyl‐1‐phosphonate), potentiate the ability of L‐dopa (L‐3,4‐dihydroxyphenylalanine) to reverse akinesia and to alleviate muscular rigidity in monoamine‐depleted rats. On the basis of these findings, it is proposed that NMDA antagonists may be beneficial as adjunctive treatment in the therapy of Parkinson's disease. CPP locally injected into the subthalamic nucleus, entopeduncular nucleus–the rat homologue of the internal pallidal segment–or substantia nigra pars reticulata of monoamine‐depleted rats stimulates locomotor activity and alleviates rigidity, whereas local microinjection of CPP into the neostriatum is ineffective. These results make it unlikely that the neostriatum is the site of the antiparkinsonian action of NMDA antagonists in monoamine‐depleted rats, whereas the subthalamic nucleus, internal pallidal segment, and substantia nigra pars reticulata appear to be important for the effects of NMDA antagonists.
Visual dysfunction in Alzheimer's disease: Relation to normal aging
Authors: Cronin‐Golomb Alice , Corkin Suzanne , Rizzo Joseph F. , Cohen Jennifer , Growdon John H. , Banks Kathleen S.
Published: January 2005

In patients with Alzheimer's disease (AD), compared with age‐matched and young healthy control subjects, visual deficits in the following functions were observed: color, stereoacuity, contrast sensitivity, and backward masking (homogeneous and pattern). Critical flicker fusion thresholds were normal, relative to age‐matched healthy subjects. For color, the majority of the errors were tritanomalous (blue axis). Color and stereoacuity deficits were unrelated to severity of dementia, in accordance with models of vision that describe these functions as modular rather than diffuse for cortical localization. Although contrast sensitivity was depressed throughout the frequency range in AD, more patients were impaired at low than at high spatial frequencies, contrasting with the observed normal aging pattern of high‐frequency loss. Healthy elderly subjects showed depressed critical flicker fusion thresholds and reduced contrast sensitivity at high frequencies, relative to the young group; differences between these groups were not found for the other vision tests. A subset of the AD group received detailed neuro‐ophthalmological examination, and no abnormalities were found. This finding, taken together with normal thresholds for critical flicker fusion, suggests that the widespread visual dysfunction reported here is more likely to be related to known pathological changes in primary visual and association cortex in AD than to changes in the retina or optic nerve.
Lymphoma, motor neuron diseases, and amyotrophic lateral sclerosis
Authors: Younger D. S. , Rowland L. P. , Latov N. , Hays A. P. , Lange D. J. , Sherman W. , Inghirami G. , Pesce M. A. , Knowles D. M. , Powers J. , Miller J. R. , Fetell M. R. , Lovelace R. E.
Published: January 2005

We studied 9 patients with motor neuron disease and lymphoma. The following several observations have not been recognized in the past: (1) Motor neuron syndromes are associated with either Hodgkin's disease or non‐Hodgkin's lymphoma. (2) The syndromes are not restricted to lower motor neuron disorders; 8 of 9 patients had definite or probable upper motor neuron signs as well, qualifying for the diagnosis of amyotrophic lateral sclerosis. Corticospinal tracts were affected in both postmortem examinations. (3) The combination of motor neuron disease and lymphoma is often accompanied by paraproteinemia (3 of 7 patients studied), increased cerebrospinal fluid protein content (6 of 9 patients), and cerebrospinal fluid oligoclonal bands (3 of 9 patients). (4) In 2 patients, asymptomatic non‐Hodgkin's lymphoma was found only because the discovery of paraproteinemia gave impetus to examine the bone marrow. (5) Patients with both upper and lower motor neuron signs (amyotrophic lateral sclerosis) may show physiological evidence of conduction block in peripheral nerves or autopsy abnormalities in peripheral nerves. The cause of this syndrome is not known. Both lymphoma and motor neuron disease could have a common cause, possibly a retroviral infection. The frequency of paraproteinemia suggests that an immunological disorder may play a role in the pathogenesis of the neurological disorder.
The predictive value of intrathecal immunoglobulin synthesis and magnetic resonance imaging in acute isolated syndromes for subsequent development of multiple sclerosis
Authors: Sharief Mohammad K. , Thompson Edward J.
Published: January 2005

The intrathecal synthesis of IgM in patients presenting with acute monosymptomatic syndromes may be relevant in predicting eventual progression to multiple sclerosis but has not been previously evaluated. We undertook a prospective 18‐month combined clinical, cerebrospinal fluid, and magnetic resonance imaging study of 45 patients who had presented with acute isolated lesions of brainstem and spinal cord to evaluate the predicive value of intrathecal synthesis of IgM and IgG (through the detection of cerebrospinal fluid oligoclonal bands) and magnetic resonance imaging brain lesions at presentation, for the subsequent progression to multiple sclerosis. Results indicate that the highest risk of developing multiple sclerosis is seen in patients who are positive for oligoclonal IgM and IgG bands and who have disseminated cerebral white matter magnetic resonance imaging lesions at the initial presentation. Oligoclonal IgM bands predict progression to multiple sclerosis more frequently than oligoclonal IgG or magnetic resonance imaging alone. Our results confirm and further extend previous reports, and indicate that detection of cerebrospinal fluid oligoclonal IgM bands at presentation is a valuable prognostic indicator in patients presenting with acute isolated brainstem or spinal cord syndromes.
Benign familial neonatal convulsions: Evidence for clinical and genetic heterogeneity
Authors: Ryan Stephen G. , Wiznitzer Max , Hollman Charlotte , Torres M. Cristina , Szekeresova Maria , Schneider Sandra
Published: January 2005

The gene for autosomal dominant “benign” familial neonatal convulsions, a transient, primary epilepsy of infancy, has recently been assigned to chromosome 20q. To determine whether this disorder is genetically heterogeneous, we performed linkage analysis in two previously unreported pedigrees with benign familial neonatal convulsions in which clinical heterogeneity was evident. There were 14 affected persons in the first family, and none had seizures (febrile or afebrile) after the age of 2 months. The second family had 13 affected individuals and 2 obligate carriers; seizures frequently did not remit until 6 to 24 months, febrile convulsions occurred in at least 2 patients, apparent audiogenic seizures occurred in 4 patients, and 1 individual had refractory epilepsy until late adolescence. Linkage studies with the chromosome 20 markers D20S19 and D20S20 were performed in both families. The resulting data favored linkage of the disease and marker loci in Family 2 by a maximum odds ratio of 45:1 at 6% recombination. In Family 1, however, the odds were greater than 20,000:1 against linkage at 10% recombination or less. We conclude that the syndrome of benign familial neonatal convulsions is clinically and genetically heterogeneous. Further study will be necessary to clarify the relationship between phenotype and genotype in this disorder.