bluuebunny/crossref_metadata_2025 huggingface dataset:
Paramedian thalamic and midbrain infarcts: Clinical and neuropathological study
Authors: Castaigne P. , Lhermitte F. , Buge A. , Escourolle R. , Hauw J. J. , Lyon‐Caen O.
Published: January 2005

The clinical and neuropathological findings in 28 cases of paramedian thalamic and midbrain infarcts are reported. The 4 instances of unilateral paramedian thalamic infarct were characterized by mood and behavioral changes, limitation of the infarct to the center of the anatomical paramedian territory, and symmetrical configuration of the paramedian thalamic arteries. Basilar artery occlusion was found in 1 patient. The 5 cases of bilateral paramedian thalamic infarcts were characterized by disturbances of consciousness and behavior, extension of the infarct (to the mammillothalamic tracts in 4 cases, the red nuclei in 3, and the hypothalamus in 2), and a variable paramedian thalamic arterial pattern. The arterial pattern was symmetrical in 2 cases, asymmetrical in 1, and unilateral in 1. The basilar artery was occluded in 1 case, the basilar communicating and posterior cerebral arteries in 1, and a third patient had occlusion involving an aneurysm of the basilar artery. The 19 patients with paramedian thalamopeduncular infarcts had marked disturbances of consciousness (hypersomnia, deep coma, akinetic mutism) associated with ocular motility changes. Later, abnormal movements—always delayed—and memory, disturbances were observed in some. Thalamic changes were restricted to the paramedian territory in only 3 cases. The arterial pattern was symmertical in 5. The basilar and posterior cerebral arteries were occluded in 4 patients each.

Paramedian infarcts were rarely found as isolated lesions and were always bilateral when there was only one arterial pedicle. The paramedian thalamic pedicle can supply the polar thalamic territory.
Neurological status of language‐impaired and normal children
Authors: Johnston Robert B. , Stark Rachel E. , Mellits E. David , Tallal Paula
Published: January 2005

The performance on a neurological test battery of 33 language‐impaired children who had no gross neurological findings and 37 normal children controlled for age, performance IQ, and socioeconomic status was compared. The language‐impaired group was distinguished by less efficient performance in a number of areas, particularly in tasks involving rate of movement, perception of dichhaptic stimuli, and left‐right identification. Discriminant function analysis identified six variables that correctly classified 87% of the population into their respective normal and language‐impaired groups.
Selective carnitine palmitoyltransferase deficiency in fibroblasts from a patient with muscle CPT deficiency
Authors: Pula T. P. , Max S. R. , Zielke H. R. , Chacon M. , Baab P. , Gumbinas M. , Reed W. D.
Published: January 2005

A 13‐year‐old boy developed cramps and myoglobinuria following exertion. Mitochondrial preparations from a skeletal muscle biopsy were deficient in carnitine palmitoyltransferase (CPT) activity when assayed by the hydroxamate and kinetic assays. The patient's fibroblasts were also deficient when assayed by the hydroxamate and kinetic assays, but not when tested by the DTNB (5′,5′‐dithiobis‐[2‐nitrobenzoic acid]) method. This disparity probably indicates a specific deficiency in fibroblasts of one of the two carnitine palmitoyltransferases, presumably CPT II.
Lysosomal abnormalities in cultured schwann cells from a patient with peripheral neuropathy and continuous muscle fiber activity
Authors: Askanas Valerie , Engel W. King , Berginer Vladimir M. , Odenwald Ward F. , Galdi Albert
Published: January 2005

Schwann cell cultures were established from a sural nerve containing large membrane‐bound vaculoes in its schwann cells, obtained from a patient with neuropathy and continuous muscle fiber activity. cultured Schwann cell contained may large membrane‐bound vaculoles, presumably lysosomes, resembling those present in the biopsied nerve. the acid phosphatase reaction was excessive in the patient's cultured schwann cells but practically negative in normal cultured Schwann cells. this study Indicates that the patient's neuropathy is primary dysschwannian with abnormal lysosomes as a major abnormality.
Computerized tomography in subacute necrotizing encephalomyelopathy (Leigh disease)
Authors: Schwartz William J. , Hutchison Harrol T. , Berg Bruce O.
Published: January 2005

The computerized tomographic brain scans of two patients with subacute necrotizing encephalomyelopthy contained symmetrical focal lesions that corresponded to the sites of known anatomical abnormalities in this disease.
A cortical network for directed attention and unilateral neglect
Authors: Mesulam M.‐Marchsel
Published: January 2005

Unilateral neglect reflects a disturbance in the spatial distribution of directed attention. A review of unilateral neglect syndromes in monkeys and humans suggests that four cerebral regions provide an integrated network for the modulation of directed attention within extrapersonal space. Each component region has a unique functional role that reflects its profile of anatomical connectivity, and each gives rise to a different clinical type of unilateral neglect when damaged. A posterior parietal component provides an internal sensory map and perhaps also a mechanism for modifying the extent of synaptic space devoted to specific portions of the external world; a limbic component in the cingulate gyrus regulates the spatial distribution of motivational valence; a frontal component coordinates the motor programs for exploration, scanning, reaching, and fixating; and a reticular component provides the underlying level of arousal and vigilance. This hypothetical network requires at least three complementary and interacting representations of extrapersonal space: a sensory representation in posterior parietal cortex, a schema for distributing exploratory movements in frontal cortex, and a motivational map in the cingulate cortex. Lesions in only one component of this network yield partial unilateral neglect syndromes, while those that encompass all the components result in profound deficits that transcend the mass effect of the larger lesion. This network approach to the localization of complex functions offers an alternative to more extreme approaches, some of which stress an exclusive concentration of function within individual centers in the brain and others which advocate a more uniform (equipotential or holistic) distribution.

In human beings, unilateral neglect syndromes are more frequent and severe after lesions in the right hemisphere. Also, right hemisphere mechanisms appear more effective in the execution of attentional tasks. Furthermore, the attentional functions of the right hemisphere span both hemispaces, while the left hemisphere seems to contain the neural apparatus mostly for contralateral attention. This evidence indicates that the right hemisphere of dextrals has a functional specialization for the distribution of directed attention within extrapersonal space.
Clinical and biochemical heterogeneity of globoid cell leukodystrophy
Authors: Farrell Donald F. , Swedberg Kathy
Published: January 2005

The residual galactosylceramide β‐galactosidase activity in cultured skin fibroblasts from a child with late‐onset globoid cell leukodystrophy (GLD) was distinctly different from that found in the typical infantile form of the disease. The residual enzyme activity and maximum velocity of the enzyme reaction were higher in this patient, while the Michaelis constant was similar in controls and in the two forms of GLD. The pH optimum of enzyme activity from the patient was similar to that of controls and a more acidic pH optimum was found in the infantile form. Cultured skin fibroblasts from the patient accumulated less [63H]‐galactosylceramide than did cells from the infantile form. These various biochemical measurements correlated well with the age of onset of the disease and suggest that different allelic mutations of the galactosylceramide β‐galactosidase locus are responsible for the different clinical forms of GLD.
Myelin basic protein in Alzheimer disease neuronal fractions and mammalian neurofilament preparations
Authors: Selkoe Dennis J. , Brown Beverly A. , Salazar Fernando J. , Marchotta Charles A.
Published: January 2005

We previously reported a marked increase of a 20,000 molecular weight (MW) protein, P20, in some neuronal fractions and whole cortical homogenates isolated from affected cortex in Alzheimer disease; P20 comigrated electrophoretically with an unidentified, major 20,000 MW protein present in human neurofilament (NF) fractions. We now report that the 20,000 MW protein is a major constituent of rodent as well as human NF fractions and that it comigrates by one‐ and two‐dimensional gel electrophoresis with purified myelin basic protein (MBP). Peptide mapping and staining with amido black confirmed the identity of the 20,000 MW protein of mammalian NF fractions as MBP. One‐ and two‐dimensional gel electrophoresis of neuronal perikaryal fractions from human cortex indicated that the increased P20 protein in Alzheimer neuronal fractions comigrates with human MBP. Deliberate contamination of cortical samples with adjacent subcortical white matter (i.e., myelin) prior to neuronal separation did not result in an increase of P20 in the neuronal fraction. On the basis of these and additional experiments, we conclude that the increase of a 20,000 MW protein in neuronal fractions and whole homogenates from affected cortex in Alzheimer disease represents MBP of intracortical origin.
Eaton‐lambert myasthenic syndrome: Long‐term treatment of three patients with prednisone
Authors: Streib Erich W. , Rothner A. David
Published: January 2005

Three patients with the myasthenic syndrome of Eaton‐Lambert (ELS) were treated with prednisone for 6 and 12 months and more than 3 years, respectively. Muscle strength increased considerably in all, reaching a peak after 3 to 4 months, and was accompanied by simultaneous electromyographic improvement. Reduction of prednisone led to deterioration in all 3 patients; strength was regained when the higher dosage of prednisone was resumed. Prednisone is an alternative form of treatment for ELS, although the mechanism for its action is unclear.
Angiographic findings in herpes zoster arteritis
Authors: MacKenzie Roderick A. , Forbes Glenn S. , Karnes William E.
Published: January 2005

Four adult patients who experienced an ipsilateral hemispheric deficit 6 to 8 weeks after having developed herpes zoster ophthalmicus were seen during a six‐month period. All four patients underwent full‐circle angiography, including study of the extracranial arteries in the three older patients. Each examination demonstrated areas of segmental constriction of arteries on the ipsilateral side; two locations that were especially affected were the A2 segment of the pericallosal artery beneath the genu of the corpus callosum and the M1 segment of the middle cerebral artery. The cerebral arteries of the opposite hemisphere and the extracranial vessels did not contain demonstrable abnormalities. Pathological studies suggest that patients with this syndrome may have a necrotizing arteritis of ipsilateral blood vessels; in patients with disseminated zoster, a granulomatous angiitis of cerebral blood vessels has been found. We propose that the pattern of angiographic abnormalities described here is characteristic of herpes zoster arteritis; furthermore, the distribution pattern of the lesions suggests that the virus may spread to these arteries via branches of the ophthalmic division of the trigeminal nerve.
Cryoglobulinemia with encephalopathy: Successful treatment by plasma exchange
Authors: Reik Louis , Korn Joseph H.
Published: January 2005

A 54‐year‐old man with essential mixed cryoglobulinemia developed a diffuse and focal encephalopathy while systemic vasculitis was active and serum cryoglobulin was markedly increased. No other cause for his encephalopathy could be determined and the diagnosis of cryoglobulinemic cerebral vasculitis was made. Treatment with plasma exchange, prednisone, and cyclophosphamide resulted in clearing of the encephalopathy and reduction in serum cryoglobulin. The onset of improvement was temporally related to the initiation of plasma exchange. Plasma exchange may have a role in the treatment of other patients with life‐threatening immune complex diseases involving the nervous system.
Cerebrospinal fluid: A selective review
Authors: Cutler Robert W. P. , Spertell Robert B.
Published: January 2005

Tenchnical advances of the past decade permit detection in the cerebrospinal fluid of many endogenous substances elaborated by the brain. Study of the composition of cerebrospinal fluid in health and disease undoubtedly will supply clues to the pathophysiology of many neurological disorders.
Neurosyphilis: Intrathecal synthesis of oligoclonal antibodies to treponema pallidum
Authors: Vartdal Frode , Vandvik Bodvar , Michaelsen Terje E. , Loe Kristian , Norrby Erling
Published: January 2005

Oligoclonal IgG was present in the cerebrospinal fluid (CSF) of each of three patients with neurosyphilis studied. Conventional serological tests disclosed reduced serum/CSF ratios of antibodies to Treponema pallidum (TP) in each patient, consistent with intrathecal production of treponemal antibodies. Antibody analyses of electrofocused specimens by an immunofixation technique disclosed intrathecal production of oligoclonal TP antibodies in all patients. Treponemal antibody light chains showed a close correlation with the light chains of the oligoclonal CSF IgG. Absorption of the CSF with TP caused removal of the oligoclonal IgG. The results provide strong evidence that the oligoclonal CSF IgG in neurosyphilis represents TP antibodies, reflecting a specific immune response in the central nervous system to the infectious agent.
Hematogenous origin of the inflammatory response in acute poliomyelitis
Authors: Wolinsky Jerry S. , Jubelt Burk , Burke Susan , Narayan Opendra
Published: January 2005

To determine the origin of the inflammatory response, and in particular the microglial rod cell response, in acute viral encephalitis, 4‐week‐old Swiss mice were injected with tritiated thymidine to label actively dividing cells prior to infection with the Lansing type 2 strain of poliovirus. As expected, the majority of polymorphonuclear and mononuclear leukocytes within the central nervous system perivascular infiltrates were shown to be hematogenous in origin. As early as 24 hours after infection, isotope‐labeled cells having light histological and ultrastructural features consistent with microglia and microglial rod cells were identified within brain parenchyma and were shown to participate in neuronophagia and formation of glial nodules. Supraependymal and suprachoroidal cells were also shown to contain the label. However, neither endothelial cells nor pericytes contained label as determined by electron microscopy. These studies support a hematogenous origin for all cellular elements of the classic inflammatory response in viral infections of brain.
Thoracic root pain in diabetes: The spectrum of clinical and electromyographic findings
Authors: Kikta Donald G. , Breuer Anthony C. , Wilbourn Asa J.
Published: January 2005

Diabetic thoracic radiculopathy has been reported rarely. Fifteen new cases, seen in an equal number of patients over a 3‐year period and confirmed by electromyographic findings, have been analyzed. All patients presented with severe abdominal or chest pain, which often was not radicular in character. The presence of dysesthesias and an abnormal sensory examination of the trunk aided diagnosis. The pain was frequently associated with marked weight loss but carried a good prognosis for recovery. Six additional patients with negative electromyographic examinations were considered to have the disorder. Diabetic thoracic radiculopathy produces a distinct syndrome and may be more common than is generally recognized.
Intrusions as a sign of Alzheimer dementia chemical and pathological verification
Authors: Fuld Paula Altman , Katzman Robert , Davies Peter , Terry Robert D.
Published: January 2005

Word intrusions, a behavioral abnormality previously observed in experimental subjects receiving anticholinergic medication as well as in patients with Alzheimer dementia (Alz), were studied as a diagnostic indicator of Alz in 29 elderly nursing home residents who later came to autopsy. Those who intruded words from one portion of a mental status test to another tended to have low levels of choline acetyltransferase in the cerebral cortex (median, 104.33,p<0.05) and large numbers of cortical senile plaques (median, 16.0,p<0.01). Immediate perseverations and “guesses” on a memory test were not counted. In another group of 38 patients for clinical neurological examination for dementia, intrusions were associated with Alz in 84% of those who exhibited them and identified 90% of patients with this presumptive diagnosis.

Word intrusion appears sufficiently characteristic of Alz to be helpful diagnostically. The association of this behavioral phenomenon with low choline acetyltransferase levels and large numbers of senile plaques suggests that these changes may be important in producing the characteristic behavioral deterioration of Alz.
Distemper and multiple sclerosis in Sitka, Alaska
Authors: Cook Stuart D. , Dowling Peter C.
Published: January 2005

The annual incidence of multiple sclerosis (MS) in Sitka, Alaska, was determined in the period 1949–1979, spanning a severe 1965 epidemic of canine distemper in the dog population. Three patients were identified, and each had the onset of MS in 1969 or 1970. This time cluster of MS is significant (p < 0.01) and was predicted by the hypothesis that MS may be linked to canine distemper virus.
Cerebral blood flow after experimental basal ganglia hemorrhage
Authors: Ropper Allan H. , Zervas Nicholas T.
Published: January 2005

The effect of cerebral hemorrhage on regional cerebral blood flow (RCBF) in awake, unrestrained rats was studied by comparing intracaudate injections of whole blood (N = 14), centrifuged blood (N = 2), and inert plastic (N = 1). RCBF was measured by the polarographic hydrogen clearance technique using chronically implanted electrodes in the cortex and caudate bilaterally.

After hemorrhage, animals became comatose and flows diminished 23 to 30% (p < 0.01) below baseline values. Recovery of RCBF to prehemorrhage values was accompanied by awakening and survival while persistently low RCBF in all regions occurred only in the 2 animals that died, suggesting that physiological changes which lower RCBF after hemorrhage may be harmful. Transient hyperfusion of the contralateral cortex occurred in 6 of 10 animals during the first 10 minutes after hemorrhage.

In all 8 animals tested daily there was significant hyperperfusion of one or both cortical regions during the second or third day after hemorrhage (mean increase in right cortex RCBF, 30%, p < 0.05; left, 45%, p < 0.01). Injection of an identical volume of plastic was not accompanied by hyperperfusion, suggesting that destruction of the caudate or addition of an inuracerebral mass was not responsible for the increase in blood flow. However, injection of centrifuged blood components caused immediate hyperperfusion, which persisted in some cortical regions on the following day. A substance in cerebral hemorrhage clot may cause increased cortical RCBF.
Shortening reaction in patients with cerebellar ataxia
Authors: Angel Ronald W.
Published: January 2005

During passive extension of the elbow, the triceps muscle normally shows a burst of electromyographic activity. This shortening reaction (SR) is known to be exaggerated in extrapyramidal disease states, but the effects of cerebellar disease are unknown. The SR was measured in both arms of a patient with hemiataxia, the unaffected arm serving as a matched control. In the ataxic arm, the SR was significantly larger and did not show the normal increase during “reinforcement.” In a patient with bilateral ataxia, the SR was grossly exaggerated as compared with the SRs in a group of normal subjects. The present findings indicate an unexpected point of similarity between cerebellar and extrapyramidal disease states, which is discussed in terms of the anatomical connections of the cerebellum and basal ganglia. The techniques used in this work provide a quantitative approach to disorders of movement and muscle tone.
PPD‐, PWM‐, and PHA‐induced interferon in stable multiple sclerosis: Association with HLA‐DW2 antigen and clinical variables
Authors: Salonen Reijo , Ilonen Jorma , Reunanen Mauri , Nikoskelainen Jukka , Salmi Aimo
Published: January 2005

Interferon production after stimulation of lymphocytes with purified protein derivative, pokeweed mitogen, and phytohemagglutinin was studied in 39 patients with stable multiple sclerosis (MS) and 39 age‐ and sex‐matched controls. Stable MS patients produced less interferon, and the number of subjects producing undetectable amounts of interferon was higher in the MS group (11/39) than in the control group (2/39). A tendency toward an association between low interferon production and HLA‐Dw2 antigen was found in MS patients. There was no clear‐cut correlation between interferon production and the duration of disease or disability of the patients. Although there was no systematic correlation of age with interferon, production patients older than 55 years tended to be very poor interferon producers.
Detection of herpes simplex virus mRNA in latently infected trigeminal ganglion neurons by in situ hybridization
Authors: Tenser Richard B. , Dawson Marilyn , Ressel Steven J. , Dunstan Marie E.
Published: January 2005

Latent infection of the trigeminal ganglion with herpes simplex virus type 2 (HSV‐2) was studied in guinea pigs by in situ DNA hybridization. Frozen ganglion sections from animals killed during the period of latent virus infection were studied under nondenaturing conditions. Some sections were treated with deoxyribonuclease (DNase) or ribonuclease (RNase) before incubation with HSV DNA probes. HSV probes consisted of viral DNA nick translated and labeled in vitro with tritiated nucleotides. Bacteriophage lambda DNA, similarly prepared, was used as a control probe. The lamba probe was negative in all situations, including HSV‐2‐infected monolayer cells in cell culture. HSV‐2 probes produced heavy label and, therefore, evidence of hybridization with HSV‐2‐infected monolayer cells. When HSV‐2 probes were incubated with latently infected ganglion sections, hybridization was detected in 71% of guinea pigs and 46% of ganglia. Label was seen only in neurons, and in positive ganglia 0.3 to 5% of neurons were labeled. The amount of label was markedly decreased by pretreatment of ganglion sections with RNase but not DNase, indicating that the DNA probes hybridized to HSV messenger RNA in the latently infected ganglia.
Complex partial seizures on closed‐circuit television and EEG: A study of 691 attacks in 79 patients
Authors: Escueta A. V. Delgado , Bacsal Fe Enrile , Treiman David M.
Published: January 2005

Automatisms of 691 complex partial seizures in 79 patients were studied on closed‐circuit television (CCTV) and by electroencephalography. Simple stereotyped perseverative automatisms such as chewing, swallowing, and fumbling with clothes or sheets followed an initial motionless stare and lapse of consciousness in type I attacks. Ambulatory automatisms, bilateral arm and leg perseverative movements, and tonic adversive head or eye movements (or both) characterized type II attacks, in which a motionless stare was not observed. Type III started with a drop attack followed by confusion, amnesia, and gradual recomposure. Some type II and III attacks are suspected to begin in areas outside the temporal lobe, while type I attacks are thought to originate from the temporal lobe. Further studies using CCTV and depth electrode recordings are necessary to verify these suspicions.
Neurons in human epileptic cortex: Correlation between unit and EEG activity
Authors: Wyler Allen R. , Ojemann George A. , Ward Arthur A.
Published: January 2005

A total of 90 neurons were recorded extracellularly from 17 awake patients undergoing craniotomy for excision of epileptogenic cortex. Relationships between single‐unit activity and gross epileptiform spikes recorded locally by the microelectrode or from the immediate overlying cortical surface by electrocorticography (ECoG) were examined. Similar relationships were also sought between interictal bursts from nearby cells when action potentials from several neurons had been recorded simultaneously by the tungsten electrodes. Although 40 single units fired action potentials in some relation to ECoG spikes, the relationships were variable between units and, often, for the same unit. For many units, action potentials were more consistently related to one phase of the local field potential recorded through tungsten microelectrodes than to the ECoG recorded from the overlying cortical surface. Synchronous firing between single units recorded simultaneously by the same microelectrode was rarely seen except at the onset of an ictal event. In addition, a high degree of synchrony between unit firing and local ECoG spikes was recorded in a few patients, but these patients had frequent focal spontaneous seizures. The data imply that in human epilepsy, unlike some animal models of the disorder, relationships between surface epileptiform events and single‐unit burst firing are not easily found in interictal recordings. The data also suggest that synchrony between unit and surface events requires a high degree of synchrony among neurons within the epileptogenic focus.
Valproate‐induced hyperammonemia
Authors: Batshaw Mark L. , Brusilow Saul W.
Published: January 2005

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 μM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 ± 1.9 (SEM) versus 23.6 ± 1.5 μM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.
Intradentate colchicine retards the development of amygdala kindling
Authors: Dasheiff Richard M. , McNamara James O.
Published: January 2005

The mechanisms underlying the kindling model of epilepsy are unknown. Presumably, an altered network of neural circuits underlie amygdala kindling. Biochemical and radiohistochemical studies have pointed to the dentate granule cells (DGC) of the hippocampal formation as a member of this altered circuit. To test the role of these cells, colchicine, a neurotoxin of DGC, was directly injected into the dentate gyrus. Prior destruction of DGC retarded the development of amygdala kindling. Destruction of DGC after kindling was completed did not reverse the kindling effect. We conclude that DGC play a key role in the development, but not the permanence, of amygdala kindling. We propose a model whereby the greater the input to the hippocampal formation, the faster limbic kindling will proceed.
Long‐term follow‐up of patients with subacute sclerosing panencephalitis treated with inosiplex
Authors: Dyken Paul R. , Swift Andrea , Durant Robert H.
Published: January 2005

During the past five years, 15 patients with subacute sclerosing panencephalitis (SSPE) were treated with inosiplex. Using a disability index specifically designed for the disease, this study monitored the course of SSPE in each patient before and during inosiplex therapy. Posttreatment follow‐up ranged from 2 to 144 months. Inosiplex had an apparently beneficial effect on morbidity and mortality in 10 of the 15 patients tested. Eight improved immediately after treatment, 2 had a delayed improvement, and 1 patient stabilized. Four patients followed a typical course for SSPE and died a mean of 9 months after onset. Treatment was not associated with adverse reactions. Due to its low risk‐benefit ratio, inosiplex is recommended for continuous use in SSPE even after extended remissions.
Reversal of debrancher deficiency myopathy by the use of high‐protein nutrition
Authors: Slonim Alfred E. , Weisberg Charlene , Benke Paul , Evans Owen B. , Burr Ian M.
Published: January 2005

A child with debrancher deficiency presented with myopathy, recurrent hypoglycemia, and growth failure. Evidence for enhanced gluconeogenesis was demonstrated by low postabsorptive gluconeogenic plasma amino acids, a marked fall in alanine during fasting, and a substantial rise in plasma glucose following protein ingestion. The patient was treated with high‐protein nocturnal intragastric therapy, which resulted in marked improvement in exercise tolerance, muscle strength and mass, electromyographic findings, and growth.
Occipitotemporal epilepsy studied with stereotaxically implanted depth electrodes and successfully treated by temporal resection
Authors: Olivier André , Gloor Pierre , Andermann Frederick , Ives John
Published: January 2005

A young woman had seizures suggestive of temporal lobe origin with some clinical features indicative of occipital onset. Electroencephalograms recorded through scalp and sphenoidal electrodes showed predominantly right posterior temporooccipital epileptogenic discharges. Stereotaxic depth electrode recordings from the right temporal and occipital lobes demonstrated that some seizures arose independently from either the temporal or occipital lobes. Most arose within the occipital lobe, but to become clinically evident, the seizure discharge had to spread to the temporal lobe. Following temporal lobe resection, including excision of limbic structures, the patient has remained seizure free for four years except for a few generalized seizures before and after delivery of her child.
Neuroimmunology I: Immunoregulation in neurological disease
Authors: Weiner Howard L. , Hauser Stephen L.
Published: January 2005

Aberrations in immune function that ultimately result in disease states may involve three aspects of immune regulation: (1) regulatory T cells, which both suppress and induce immune responses; (2) idiotype‐antiidiotype networks, which serve as internal regulatory networks during generation of an immune response; and (3) immune response genes, which determine genetic differences in an individual's immune response. Three major diseases of the nervous system, multiple sclerosis, myasthenia gravis, and acute inflammatory polyneuropathy (Guillain‐Barré syndrome), are classified as “autoimmune” in nature and may be due to underlying disorders of immunoregulation. In multiple sclerosis there is a loss of suppressor T cells in the peripheral blood during attacks, in myasthenia gravis there are thymic abnormalities and antibodies against the acetylcholine receptor, and in acute inflammatory polyneuropathy, macrophage‐mediated destruction of peripheral nerve myelin occurs in the context of sensitized T cells and is usually associated with a preceding viral illness. In each of these disease the following central questions must be answered: (1) against what antigen (or antigens) of the nervous system is the autoimmune response directed? (2) what is the mechanism of immune damage? and (3) what initiates, or triggers, the autoimmune response?
Temporal profile of neuronal damage in a model of transient forebrain ischemia
Authors: Pulsinelli William A. , Brierley James B. , Plum Fred
Published: January 2005

This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four‐vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion‐fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four‐vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium‐sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3–5, paramedian zone) increased significantly (p < 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracte increase in its incidence between 24 and 72 hours could reflect either delayed‐appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.
Ocular tilt reaction due to an upper brainstem lesion: Paroxysmal skew deviation, torsion, and oscillation of the eyes with head tilt
Authors: Hedges Thomas R. , Hoyt William F.
Published: January 2005

A patient with a focal brainstem abscess in the region of the zona incerta developed a chronic oculocephalic dyskinesia in which paraoxysmal tonic skew deviation and torsion of the eyes were coupled with ocular oscillations and head tilt.
Slowly progressive aphasia without generalized dementia
Authors: Mesulam M.‐Marsel
Published: January 2005

Six right‐handed patients experienced a slowly progressing aphasic disorder without the additional intellectual and behavioral disturbances of dementia. The symptoms almost universally started in the presenium. The initial difficulty was an anomic aphasia in five of the patients and pure word deafness in the sixth. Continuous and gradual deterioration occurred in the five patients who presented with an anomic aphasia. They eventually experienced additional impairment of reading, writing, and comprehension. In four patients, other areas of comportment were not involved within the 5 to 11 years of follow‐up. A more generalized state of dementia may have emerged in the other two patients, but only after 7 years of progressive and debilitating aphasia. Neurodiagnostic procedures were consistent with preferential involvement of the left perisylvian region. In one patient, cortical biopsy did not show any pathognomonic change; specifically, no neurofibrillary tangles, amyloid plaques, neuronal inclusions, or gliosis were seen. This condition may constitute a syndrome of relatively focal cerebral degeneration with a predilection for the left perisylvian region.
Neurological complications of immunization
Authors: Fenichel Gerald M.
Published: January 2005

Vaccines prepared from whole, killed organisms (pertussis and possible influenza) may cause neurological allergic reactions producing encephalopathy. These reactions are characterized by acute, monophasic demyelinative processes and occur with no greater frequency than 1 per 100,000 vaccine recipients; onset is within 4 days of immunization, and recovery is usually complete. No evidence suggests that these vaccines produce an insidious, progressive encephalopathy. Only with the swine influenza program of 1976 has Guillain‐Barré syndrome appeared to follow immunization.

Vaccines prepared from live‐attenuated viruses (measles, mumps, rubella, and trivalent oral poliovirus) can cause symptomatic viral infection of the nervous system, including measles encephalitis, which occurs in 1 of 1,000,000 vaccine recipients; rubella neuritis, in less than 1 of 10,000 recipients; and paralytic poliomyelitis, in 1 of 3,000,000 vaccine recipients or their close contacts. A cause‐and‐effect relationship between immunization and brachial plexus neuritis, acute transverse myelitis, and cranial neuropathies has been suggested by never proved.
Prostaglandin I2, indomethacin, and heparin promote postischemic neuronal recovery in dogs
Authors: Hallenbeck J. M. , Leitch D. R. , Dutka A. J. , Greenbaum L. J. , McKee A. E.
Published: January 2005

Forty‐five conditioned male mongrel dogs were exposed to multifocal ischemia sufficient to maintain suppression for 60 minutes of the P1–N1 amplitude of the cortical sensory evoked response (CSER), a quantifiable index of neuronal function. Ischemia was induced and regulated by successive embolization of 20 to 50 μl increments of air via the right internal carotid artery. Subsequently, the P1–N1 amplitude recovery of the CSER was followed for an additional 15, 60, or 120 minutes while the dogs were treated or left untreated. The combination of prostaglandin I2 (PGI2), indomethacin, and heparin promoted a statistically significant augmentation of return of CSER amplitude relative to no treatment, PGI2 alone, indomethacin alone, PGI2 and heparin, indomethacin and heparin, or PGI2 and indomethacin. After 60 minutes of recovery, animals receiving combined PGI2, indomethacin, and heparin achieved a 57% recovery of P1–N1 amplitude relative to baseline, while the corresponding recoveries in all other groups clustered around 20%. By 120 minutes of postischemic follow‐up, the CSER recovery induced by PGI2, indomethacin, and heparin was 80% compared to 17% in untreated animals. By 15 minutes into the recovery period, the combination of the three agents had eliminated very low flows in the “neuron‐disabling” range (defined as 0 to 15 ml/100gm/min for gray matter and 0 to 6 ml/100gm/min for white matter) in contrast to the relative inefficacy of no treatment or treatment with other than the triple combination of drugs. The study lends some support to a planned clinical trial of PGI2, indomethacin, and heparin in acute occlusive stroke in humans.
Neurotoxicity of the pyrimidine synthesis inhibitor N‐phosphonoacetyl‐L‐aspartate
Authors: Wiley R. G. , Gralla R. J. , Casper E. S. , Kemeny N.
Published: January 2005

PALA (N‐phosphonoacetyl‐L‐aspartate) impairs de novo pyrimidine biosynthesis by inhibiting the enzyme aspartate transcarbamylase. During cancer chemotherapy trials the drug was given by weekly intravenous infusion. Seizures developed in 9 (11%) of the first 80 patients to receive a total dose of 9 gm/m2 or more. Seven of the affected patients had structural brain lesions; they developed seizures at a lower total dose (median of 16.4 gm/m2) than the 2 patients without clinically detectable brain lesions (115 to 130 gm/m2). Reversible encephalopathy was observed in 6 (7.5%) additional patients without clinically detectable cause other than PALA. Both seizures and encephalopathy began after the second dose of PALA or later. Experiments in rats demonstrated similar delayed‐onset seizures after two or three combined systemic and intracerebral doses of PALA at 4‐day intervals. Concurrent administration of uridine or carbamyl aspartate prevented the development of seizures in rats, indicating that pyrimidine starvation of the central nervous system was responsible for PALA neurotoxicity.
Tetrabenazine has properties of a dopamine receptor antagonist
Authors: Login Ivan S. , Cronin Michael J. , MacLeod Robert M.
Published: January 2005

Tetrabenazine is considered to act in a manner similar to reserpine to reduce the involuntary movements of tardive dyskinesia or Huntington's disease and to improve psychoses. We determined that tetrabenazine also has properties of a dopamine receptor antagonist by testing the ability of tetrabenazine to block the inhibitory effect of dopamine on prolactin secretion from rat anterior pituitary glands in vitro and to displace3H‐spiperone binding to dopamine receptors in the pituitary, corpus striatum, and a rat transplantable prolactin‐secreting tumor. Under in vitro conditions, 0.5 to 10 μM tetrabenazine directly blocked dopaminergic inhibition of prolactin secretion. Furthermore, 1 hour after tetrabenazine injection (30 mg/kg intraperitoneally) in vivo, when the serum prolactin had increased from 22 ± 9 to 450 ± 52 ng/ml (p< 0.01), pituitary glands of the treated rats examined in vitro were refractory to dopaminergic inhibition of prolactin release. Tetrabenazine apparently interacts with the dopamine receptor, because this drug displaced the dopamine antagonist3H‐spiperone from dopamine receptors of the three different tissues with an apparent inhibitory constant of about 5 μM. We conclude that tetrabenazine has biological and pharmacological properties typical of a dopamine receptor antagonist. These observations should stimulate a reevaluation of the mechanisms for the actions of tetrabenzine previously attributed exclusively to a “reserpine‐like” effect.
Complement activation in muscle fiber necrosis: Demonstration of the membrane attack complex of complement in necrotic fibers
Authors: Engel Andrew G. , Biesecker Gregory
Published: January 2005

The membranolytic C5b‐9 complement membrane attack complex (MAC) is assembled after activation of either the classic or the alternative complement pathway. The quaternary configuration of the MAC macromolecule presents neoantigenic determinants not present on precursor molecules. Consequently, antibodies specific for these neoantigen(s) do not detect nonspecifically bound native complement precursors of MAC. By means of antibodies rendered specific for MAC neoantigen(s), MAC was localized by the immunoperoxidase reaction in cryostat sections of human muscle. In 66 biopsy specimens containing necrotic muscle fibers (Duchenne dystrophy, 13; other dystrophies, 15; inflammatory myopathies, 31; miscellaneous myopathies, 7) all of the necrotic fibers reacted for MAC neoantigen(s). C3 and C9 were also consistently localized in necrotic fibers, but localization of C1q, C4, and IgG was variable and often did not exceed background staining. None of the nonnecrotic fibers reacted for immunoglobulin or complement. Detection of MAC neoantigen(s) in necrotic fibers in a wide variety of muscle diseases unambiguously shows that (1) the lytic complement pathway is consistently activated and participates in muscle fiber necrosis in vivo, and (2) complement reaction products are generated that can stimulate cellular infiltration and phagocytosis of the necrotic fiber. The findings also suggest that cell necrosis in general may involve participation of complement.
Immune regulation in myasthenia gravis: Evidence for an increased suppressor T‐cell population
Authors: Miller Andrea E. , Hudson James , Tindall Richard S. A.
Published: January 2005

The production of anti‐acetylcholine receptor antibodies in myasthenia gravis represe‐hyphen;ts a peresents a persistent and unexplained break in self‐tolerance. The studies reported here demonstrate an altered regulatory T‐cell population with an increase in the percentage of circulation T‐suppress cells as defined by two independently developed murine Monoclonal antibody markers. Leu 2a‐ and OKT8a‐positive cells were significantly increased within the T‐cell population in myasthenia gravis (25.0 ± 6.4% versus 20.7 ± 2.9% and 34.9 ± 7.0% versus 26.0 ± 3.2%, respectively) compard to an age‐ and sex‐equivalent group. In addition, the circulating total T‐cell population was reduced in myasthenia gravis. Patients with symptomatically uncontrolled disease (with or without immunosuppression) demonstrated significantly altered ratios of helper to suppressor T‐cells, while patients whose myasthenia symptoms were controlled did not differ from normal subjects.
Reciprocal excitation of antagonistic muscles as a differentiating feature in spasticity
Authors: Myklebust Barbara M. , Gottlieb Gerald L. , Penn Richard D. , Agarwal Gyan C.
Published: January 2005

The electromyographic activity evoked by forced ankle rotation in spastic patients with cerebral palsy differs markedly from that found in normal subject or in patients with adult‐onset injuries to the central nervous system. Rapid dorsiflexion can produce a strong myotatic reflex electromyogram at 30 to 50 msec in the normal adult's stretched soleus muscle, while the antagonist tibialis anterior muscle remains quiet. The same is true of spastic patients whose injury has an adult onset. In patients with cerebral palsy this early response is found in both muscle groups. The pattern of “reciprocal excitation” is in marked contrast to the reciprocal inhibition normally seen. This reflex behavior suggests a fundamental developmental error in neuronal interconnections of the spinal cord in cerebral palsy.
Treatment of the “on‐off” phenomenon in parkisnonism with lithium carbonate
Authors: Coffey C. Edward , Ross Donald R. , Ferren E. L. , Sullivan John L. , Olanow C. Warren
Published: January 2005

Six patients with severe parkinsonism complicated by the “on‐off” phenomenon were treated with lithium carbonate in addition to regular antiparkinsonian medications. A randomized double‐blind crossover trial of lithium versus placebo was conducted, followed by an open trial of lithium therapy. Five patients had marked reductions in akinesia (mean, 70%) and improved by one grade in parkinson staging. This result was more striking in male than in female patients, and in all responders benefit has been maintained during the open phase of lthium treatment (mean follow‐up of 36 weeks). In no patient was reduction in akinesia observed during placebo treatment. Lithium carbonate appears to offer a new and potentially effective approach to treatment of the on‐off phenomenon.
Tomographic mapping of human cerebral metabolism: Sensory deprivation
Authors: Mazziotta John C. , Phelps Micael E. , Carson Richard E. , Kuhl David E.
Published: January 2005

Local cerebral glucose metabolism was measured in 22 right‐handed, normal volunteers using 18F‐fluorodeoxyglucose and positron computed tomography. Three states consisting of selective or combined auditory or visual deprivation were examined. Results demonstrated a progressive decline in overall glucose metabolism with reduced sensory inputs. The relative metabolism of the frontal cortex compared to that of the parietal and occipital cortex progressively increased from the eyes‐closed to the ears‐closed to the both‐closed states. Left‐right symmetry was found throughout the distribution of structures within the region of brain sampled for both the selective auditory and visual deprivation test conditions, but a relative decrease in right‐sided metabolism occurred in the combined audiovisual deprivation state. The most significant metabolic asymmetries occurred in the perisylvian, inferior prefrontal, and lateral occipital cortex. The relative metabolic rates of the medial occipital cortex, measured as a percentage of the hemispheric mean, doubled bilaterally with eye opening. The results demonstrate the difficulties inherent in defining a stable and reproducible “resting” state for the human brain.
Selective reduction of blood flow to white matter during hypotension in newborn dogs: A possbile mechanism of periventricular leukomalacia
Authors: Richard S. K. Young , Hernandez Milton J. , Yagel Susan K.
Published: January 2005

The cerebrovascular response of newborn animals to hypotension has not been defined on a regional basis. Using an autoradiographic technique employing 14C‐iodoantipyrine as indicator, we studied the cerebral physiological responses of newborn dogs to hypotension induced by exsanguination or by administration of Escherichia coli endotoxin. Regional cerebral blood flow (rCBF) to all gray matter structures was preserved, even at mean arterial pressures as low as 20 mm Hg. In contrast, rCBF to periventricular and occipital white matter decreased significantly during severe hypotension. The selective hypoperfusion of cerebral white matter during severe hypotension may provide a mechanistic explanation for the pathogenesis of periventricular leukomalacia.