bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased prevalence and titer of Epstein‐Barr virus antibodies in patients with multiple sclerosis
Authors: Sumaya Ciro V. , Myers Lawrence W. , Ellison George W. , Ench Yasmin
Published: January 2005

The prevalence and titer of serum antibodies to several Epstein‐Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non‐blood‐related subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control group. A greater number of reduced ratios of serum: CSF IgG antibody to EBV‐capsid antigen and antibody to EBV‐early antigen components than to adenovirus, a referemce or control virus, were found in the multiple sclerosis group. Reduced ratios of these Ebv antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the result of an earlier report and strengthen the association between EBV and multiple sclerosis.
Motor neuron disease and adult hexosaminidase a deficiency in two families: Evidence for multisystem degeneration
Authors: Mitsumoto Hiroshi , Sliman Robert J. , Schafer Irwin A. , Sternick Cary S. , Kaufman Benjamin , Wilbourn Asa , Horwitz Samuel J.
Published: January 2005

We studied three patients from two unrelated families with adult hexosaminidase A deficiency. A 30‐year‐old, non‐Jewish proband in the first family had juvenile amyotrophic lateral sclerosis that evolved to mild demetia, ataxia, and axonal (neuronal) motor‐sensory peripheral neuropathy. A 36‐year‐old Jewish proband in the second family had “pure” spinal muscular atrophy. One supposedly healthy brother of the first proband was found to have borderline IQ, mild spasicity, ataxia but no evidence of motor neuron disease. Marked cerebellar atrophy was detected by head scans in all three patients. In both probands electromyograms were chacteriszed prominent, complex repetitive discharges in many muscles. Hexosaminidase A activities against the artificial substrate were similar to those reported in infantile Tay‐Sachs disease; however, the hexosaminidase A level against GM2 substrates was higher than that found infantile Tay‐Sachs disease. The hexosaminidase A levels of the parents were in the heterozygous range. Motor neuron disease in our patients and in those previously described appears to be park of a multisystem degeneration of the nervous system.
Leptomeningeal metastases: Peripheral nerve and root involvement—clinical and electrophysiological study
Authors: Argov Zohar , Siegal Tali
Published: January 2005

Twenty‐five patients with revently diagnosed leptomeningeal metastases underwent a prospective clinical and electrophysiological study to assess the mode and extent of peripheral nerve and spinal root invlovement. Motor conduction velocities and F wave latencies in the legs were found frequently to be disturbed compared with normal subjects and a control group of cancer patients. F wave changes were the most sensitive indicator of root involvement. Electrophysiological abnormalities were detected in 20 patients, compared with 15 who had abnormal clinical signs suggesting peripheral nerve dysfunction. Electrophysiological studies can be useful in the evaluation of patients with suspected leptomeningeal metastases, and repeated recording of F wave latencies may serve to indicate root recovery in a clinically stable patient.
Electroencephalographic spiking activity, drug levels, and seizure occurence in epileptic patients
Authors: Gotman J. , Marciani M. G.
Published: January 2005

We investigated the relationship among the electroencephalographic spiking rate, drug levels, and seizure occurence in 44 patients with focal epilepsy. Seizure occurence was continuously monitored by personnel or videorecording and spiking rate quantified by an atuomatic detection method. Results indicate that drug levels do not influence spiking rate, and spiking rate does not change before seizures but increases markedly after them, particularly secondarily generalized seizures. This increase can last several days and is observed during wakefulness and sleep. High or low spiking rates do not influence the occurence of seizures. We suggest that interictal spikes may passively reflect damage to the brain, a damage which worsened by further seizures. Spikes may not be directly related to seizure generation.
31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog
Authors: Young Richard S. K. , Osbakken Mary D. , Briggs Richard W. , Yagel Susan K. , Rice David W. , Goldberg Stuart
Published: January 2005

The effects of prolonged bicuculline‐induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes.
Evoked potential testing in relatives of multiple sclerosis patients
Authors: Nuwer Marc R. , Visscher Barbara R. , Packwood James W. , Namerow Norman S.
Published: January 2005

Evoked potential (EP) tests were obtained in 110 neurologically normal first‐degree relatives of patients with multiple sclerosis. Visual EP tests were performed in all relatives; brainstem auditory and median nerve somatosensory EP tests were performed in 67 relatives. The relatives had a mean visual EP P100 latency that was significantly longer than that for normal subjects controlled for age and gender. Asymmetries were seen in results from individual MS relatives, including interocular visual EP P100 differences of up to 14 ms, and interarm somatosensory Erb‐N18 differences of up to 3.0 ms. We identified 19 pairs of patients and relatives who were HLA identical and 18 other pairs who were HLA double nonmatched. EP asymmetries were seen more often in the HLA identical siblings than in the HLA double nonmatched siblings. This suggests that subclinical, focal, and electrophysiological changes do occur in relatives of MS patients, especially if they share HLA types with the patients. Since less than 2% of siblings of MS patients would be expected to eventually develop clinical MS, these small subclinical electrophysiological changes are not expected to be a sign of the future appearance of clinical MS. Clinicians should be aware not to overinterpret small EP changes in relatives of MS patients.
Cytomegalovirus and herpes simplex virus ascending myelitis in a patient with acquired immune deficiency syndrome
Authors: Tucker Tarvez , Dix Richard D. , Katzen Carolyn , Davis Richard L. , Schmidley James W.
Published: January 2005

Progressive ascending myelitis was the presenting feature of the acquired immune deficiency syndrome (AIDS) in a homosexual man who also had Kaposi's sarcoma, Pneumocystis pneumonia, and disseminated cytomegalovirus (CMV) infection. Neuropathological studies showed profuse cytomegalic cells throughout the brain and spinal cord, but no inflammatory response. At postmortem examination, CMV and herpes simplex virus, type 2 (HSV‐2), were recovered from multiple sites throughout the central nervous system (CNS). HSV‐2 was isolated from the anus, but from no other extraneural site; in contrast, pathology typical of CMV was also seen in the liver, gastrointestinal tract, adrenals, and lungs. Although histopathological evidence suggesting prior CMV infection has been seen in the brains of AIDS patients, the virus has never been cultured from the CNS in these immunosuppressed hosts, nor has it been known to infect the spinal cord. The absence of an inflammatory response suggests that the pathogenesis of CNS viral infections is altered in AIDS patients. Evidence for CMV infection of the CNS in AIDS patients is no longer circumstantial.
Serum prolactin and cortisol levels in evaluation of pseudoepileptic seizures
Authors: Pritchard Paul B. , Wannamaker Braxton B. , Sagel Julius , Daniel Charlene M.
Published: January 2005

In 6 patients with epilepsy, a twofold increase in serum prolactin levels followed true epileptic seizures, but no significant change followed pseudoepileptic attacks in 6 other patients. Serum prolactin concentration is a useful biochemical marker to distinguish between epileptic and pseudoepileptic seizures. Serum cortisol levels also increased after epileptic seizures, but diurnal and individual variations render the cortisol level a less reliable indicator of such attacks.
Human cutaneous mechanoreceptors during regeneration: Physiology and interpretation
Authors: Mackel Robert
Published: January 2005

Percutaneous microneurography was used to record activity from single cutaneous afferents reinnervating the glabrous skin of the hand. Recordings were obtained from 6 months to 10 years after complete transsection of the median and/or ulnar nerves with subsequent repair. Transitional properties in the discharge behavior and receptive field characteristics of regenerating afferents were detected during the early stages of regeneration, when axonal maturation was still in progress; these may contribute to the slow time course of sensory recovery. Properties of reinnervated receptors long after nerve repair, when regeneration can be considered complete, indicated a correlation between electrophysiological findings and the final state of clinical recovery. The insights into the neural basis of sensory deficits provided by single‐unit microneurography are not yielded by conventional study of the compound action potentials. This technique reveals new information about the pathophysiological nature of peripheral nerve injury and leads to a reinterpretation of clinical deficits.
Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy
Authors: Arnold D. L. , Taylor D. J. , Radda G. K.
Published: January 2005

Abnormal mitochondria are an increasingly recognized cause of neuromuscular disease. We have used phosphorus magnetic resonance spectroscopy to monitor noninvasively the metabolism of high‐energy phosphates and the intracellular pH of human skeletal muscle in vivo in 12 patients with mitochondrial myopathy. At rest, an abnormality could be demonstrated in 11 of 12 patients. Ten patients had evidence of a reduced muscle energy state with at least one of the following abnormalities: low phosphorylation potential, low phosphocreatine concentration, high adenosine diphosphate concentration, or high inorganic phosphate concentration. Two patients had abnormal resting muscle intracellular pH. In some patients phosphocreatine concentration decreased to low values during exercise despite limited work output. This was not accompanied by particularly severe intracellular acidosis. Evidence of impaired rephosphorylation of adenosine diphosphate to adenosine triphosphate during recovery from exercise was found in approately half the patients. Phosphorus magnetic resonance spectroscopy is useful in the noninvasive diagnosis of mitochondrial myopathies and in defining the pathophysiological basis of these disorders.
Neurotransmitter receptor alterations in Huntington's disease: Autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes
Authors: Whitehouse Peter J. , Trifiletti Rosario R. , Jones Bruce E. , Folstein Susan , Price Donald L. , Snyder Solomon H. , Kuhar Michael J.
Published: January 2005

In vitro receptor autoradiography was used to construct semiquantitative maps of subtypes of muscarinic cholinergic (labeled with [3H]N‐methylscopolamine), benzodiazepine ([3H]flunitrazepam), γ‐aminobutyric acid ([3H]muscimol), dopamine, and serotonin ([3H]spiperone) receptors in frontal cortex, parietal cortex, caudate, putamen, and globus pallidus in tissue sections from 5 patients with clinically well‐evaluated Huntington's disease and 5 controls matched with respect to age, sex, and postmortem delay. Homogenates were prepared from the remaining cortical and striatal tissue and used to characterize pharmacologically these same receptors, as well as histamine, adenosine, and nitren‐dipine receptors. Neuronal loss and gliosis were assessed in the contralateral formalin‐fixed caudate and putamen. All binding sites measured (except serotonin) were reduced relative to control values in striatum primarily because of changes in the number of receptors rather than in affinity. Autoradiographic studies generally revealed that these changes were greater in the caudate than the putamen, paralleling the more severe neuropathological changes present in the caudate. In addition, autoradiographic studies demonstrated an increase in γ‐aminobutyric acid‐related receptors in the globus pallidus. In the cortex, receptor alterations were limited to an increase in the number of benzodiazepine receptors in the frontal cortex which was most prominent in superficial cortical layers.
Developmental dyslexia: Four consecutive patients with cortical anomalies
Authors: Galaburda Albert M. , Sherman Gordon F. , Rosen Glenn D. , Aboitiz Francisco , Geschwind Norman
Published: January 2005

We report the neuroanatomical findings in 4 consecutively studied brains of men with developmental dyslexia. The patients, who ranged in age between 14 and 32 years, were diagnosed as dyslexic during life. Nonrighthandedness and several autoimmune and atopic illnesses were present in the personal and family histories. All brains showed developmental anomalies of the cerebral cortex. These consisted of neuronal ectopias and architectonic dysplasias located mainly in perisylvian regions and affecting predominantly the left hemisphere. Furthermore, all brains showed a deviation from the standard pattern of cerebral asymmetry characterized by symmetry of the planum temporale. The neuroanatomical findings in these 4 patients are discussed with reference to developmental cortical anomalies, cerebral asymmetries, reorganization of the brain after early lesions, and the association between learning disorders, left handedness, and diseases of the immune system.
Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management
Authors: Tandan Rup , Bradley Walter G.
Published: January 2005

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the motor system in adults that occurs in sporadic, familial, and Western Pacific forms. Involvement of non‐motor pathways has been increasingly recognized, both clinically and pathologically. Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end‐plates reveal small or absent nerve terminals. Subclinical non–motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non‐motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.
Bilateral and limited amygdalohippocampal lesions causing a pure amnesic syndrome
Authors: Duyckaerts C. , Derouesne C. , Signoret J. L. , Gray F. , Escourolle R. , Castaigne P.
Published: January 2005

A pure amnesic syndrome of 21 months' duration occurred in a 36‐year‐old man following a transient confusional state. The patient died of Hodgkin's disease. At postmortem examination, bilateral and symmetrical neuronal loss, without inflammatory changes, was restricted to the hippocampus and amygdaloid bodies.
Detection of picornavirus sequences in nervous tissue of amyotrophic lateral sclerosis and control patients
Authors: Brahic M. , Smith R. A. , Gibbs C. J. , Garruto R. M. , Tourtellotte W. W. , Cash E.
Published: January 2005

We used in situ hybridization to look for picornavirus ribonucleic acid (RNA) sequences in frozen sections of central nervous system (CNS) tissue of amyotrophic lateral sclerosis (ALS) and control patients. Using reconstruction experiments, we concluded that 30 copies of viral RNA per cell could be detected with the assay. RNA which hybridized to DNAs complementary (cDNAs) to both poliovirus and Theiler's virus was found at several levels in the CNS of 2 patients, 1 ALS patient, and 1 control. In transverse sections of the spinal cord, these sequences predominated in cells of the anterior horns. We assessed the specificity of hybridization by several criteria: (1) no hybridization was observed with heterologous visna virus cDNA probes; (2) hybridization was abolished by pretreatment of the sections with ribonuclease; (3) chemography artifacts were ruled out; and (4) the results were reproduced in three independent experiments. We concluded that RNA molecules, possibly belonging to a picornavirus having sequences in common with poliovirus and Theiler's virus, were present in the CNS of these 2 patients. On the other hand, 14 cases of classic ALS, 2 cases of Guamanian parkinsonian dementia, and 5 controls had negative results. However, the presence of picornavirus sequences in our series could be underestimated because in many cases autolysis times were 10 hours or longer.
Leukotrienes increase blood‐brain barrier permeability following intraparenchymal injections in rats
Authors: Black Keith L. , Hoff Julian T.
Published: January 2005

To examine whether leukotrienes could increase blood–brain barrier permeability, rats were anesthetized and injected intravenously with Evans blue. Ten microliters of vehicle, of leukotrienes B4, C4, or E4, or of arachidonic acid was injected over 1 hour directly into the brain parenchyma. The percentage of the total surface area of Evans blue extravasation in a coronal section of brain centered on the injection site was then determined as an estimate of blood–brain barrier permeability. Leukotrienes B4, C4, and E4, and arachidonic acid all increased blood–brain barrier permeability, but this effect was lost when the total dose was reduced to 20 ng. Increased blood–brain barrier permeability induced by arachidonic acid could be prevented by pretreatment with the lipoxygenase inhibitor BW755C, but not with indomethacin. Leukotrienes may play a role in the development of increased blood–brain barrier permeability after cerebral injury.
Similarity of brain CT appearance in spongy degeneration to that of subacute necrotizing encephalomyelopathy
Authors: Lo Warren D. , Sander James E. , Koenigsberger M. Richard
Published: January 2005

Reports of brain computed tomography (CT) findings in spongy degeneration describe radiolucent changes of the cerebral white matter, but have not described changes in the posterior fossa. We describe an infant with spongy degeneration in whom CT scans detected brainstem, cerebellar, and cerebral white matter radiolucencies before the diagnosis was established. The posterior fossa CT findings resembled the periventricular changes described in subacute necrotizing encephalomyelopathy (SNE). As the patient's initial clinical findings were consistent with SNE, the similarity of the posterior fossa radiolucencies was misleading. Without basal ganglia or thalamic involvement, or without variability in their appearance over time, posterior fossa periventricular radiolucencies are not diagnostic of a specific degenerative disorder.
The auditory pathology of brain death as revealed by auditory evoked potentials
Authors: Kaga Kimitaka , Takamori Akiyu , Mizutani Toshio , Nagai Taiji , Marsh Roger R.
Published: January 2005

A case of brain death is reported in which the auditory brainstem response, middle latency component, and slow vertex response were recorded before and after the cessation of cortical activity, and in which histological examination of the temporal bone and central auditory pathways was performed post mortem. Brain death of at least 48 hours' duration was demonstrated by neurological examination, flat electroencephalographic recording, and persistent absence of auditory evoked responses. The postmortem examination was performed 3 hours after death. The pathological studies of the whole length of the auditory pathway revealed total autolysis of the organ of Corti, marked cell loss in the dorsal cochlear nucleus, and moderate cell loss in other nuclei of the central auditory pathway. It should be considered that total autolysis of the organ of Corti and severe cell loss of the cochlear nucleus may occur if the auditory brainstem response becomes absent in comatose patients.
Amyotrophic leteral sclerosis: Part 2. Etiopathogenesis
Authors: Tandan Rup , Bradley Walter G.
Published: January 2005

The pathogenesis of the motor neuronal degeneration in amyotrophic lateral sclerosis (ALS) is unclear, though several possible etiological factors are currently being investigated. A unifying hypothesis will have to explain the diverse geographical occurrence, clinical features, and selective vulnerability and relative resistance of different neuronal populations in the disease. It is possible that different biochemical defects underlie this diversity, or alternatively that the many factors incriminated in the etiology may act upon an underlying genetic–biochemical abnormality to trigger premature neuronal death. Viruses, metals, endogenous toxins, immune dysfunction, endocrine abnormalities, impaired DNA repair, altered axonal transport, and trauma have all been etiologically linked with ALS, but convincing research evidence of a causative role for any of these factors is yet to be demonstrated.
Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis
Authors: Hafler David A. , Buchsbaum Marion , Johnson David , Weiner Howard L
Published: January 2005

A single‐cell cloning technique was used to analyze both phenotype and function of individual T cells in patients with multiple sclerosis (MS). Blood and cerebrospinal fluid (CSF) lymphocytes were plated at 1 cell per well, stimulated with phytohemagglutinin followed by interleukin 2, and expanded to 3 × 106 cells per “clone.” More than 90% of the T8 clones generated from patients with MS and controls in both blood and CSF were cytotoxic precursors. There was also a slight decrease in cytotoxic T4 clones in the blood of patients with MS. The cytotoxic precursor frequencies of T cells in the CSF generally reflected those in the blood. In separate experiments, antigen reactivity was examined in lines established from blood or CSF. No reactivity to myelin basic protein or white matter was found in patients with MS or controls. Myelin basic protein–reactive clones could, however, be generated after first stimulating lymphocytes with antigen before cloning. These results suggest that changes in the T8 population from the blood of patients with MS involve cytotoxic as well as suppressor cells. Sequestration of myelin basic protein–or white matter–reactive T cells was not seen in the CSF of patients with MS, unlike reports of viral meningoencephalitis, in which large numbers of antigen‐specific cells were found in the CSF. Direct single‐cell clonal analysis of the CSF should provide a more sophisticated approach to the study of T cell abnormalities in patients with MS.
α‐1 antitrypsin phenotypes in demyelinating disease: An association between demyelinating disease and the allele PiM3
Authors: McCombe P. A. , Clark P. , Frith J. A. , Hammond S. R. , Stewart G. J. , Pollard J. D. , McLeod J. G.
Published: January 2005

α‐1 Antitrypsin, the major circulating protease inhibitor, has more than thirty alleles that can be identified by electrophoresis. In addition to its role as a protease inhibitor, α‐1 antitrypsin may regulate the immune response. As there is evidence that both the inflammatory polyneuropathies and multiple sclerosis have an immune basis, and that genetic factors influence susceptibility, we have determined the α‐1 antitrypsin phenotypes (protease inhibitor types) of 63 patients with Guillain‐Barré syndrome, 52 patients with chronic inflammatory demyelinating polyneuropathy, and 178 patients with multiple sclerosis. In all 3 groups there was a significant increase in the proportion of patients with the protease inhibitor type M3 allele.
Stress‐induced neurological impairments in an animal model of parkinsonism
Authors: Snyder Abigail M. , Stricker Edward M. , Zigmond Michael J.
Published: January 2005

Adult rats were given the neurotoxin 6‐hydroxydopamine (6‐HDA) by means of cerebrospinal fluid to produce large dopamine‐depleting brain lesions. Although the animals behaved normally in their home cages, they became akinetic after such treatments as glucoprivation, tail shock, and exposure to severe cold. The neurological impairments were related both to the extent of dopamine depletion and to the intensity of the stress. Drugs known to enhance dopaminergic function were found to reverse the stress‐induced neurological deficits, while dopaminergic antagonists potentiated the debilitating effects of stress. After focal lesions were produced by injecting 6‐hydroxydopamine directly into specific brain regions, stress‐induced akinesia was found to correlate best with dopamine depletion in the corpus striatum, especially the lateral portion of that structure. These and other findings suggest that the acute emergence of parkinsonian symptoms during stress may reflect extensive damage to the dopaminergic nigrostriatal pathway that had been concealed in a preclinical phase, owing to compensatory neurochemical changes in the dopaminergic neurons that yet remain intact.
Aspergillosis of the central nervous system: Clinicopathological analysis of 17 patients
Authors: Walsh Thomas J. , Hier Daniel B. , Caplan Louis R.
Published: January 2005

The clinical, laboratory, and pathological features of aspergillosis of the central nervous system (CNS) were studied in a series of 17 autopsied patients. Two groups were defined. Group A consisted of 8 patients with diseases commonly associated with CNS aspergillosis: leukemia, lymphoma, aplastic anemia, and renal transplantation. Group B contained 9 patients with various illnesses not generally known to be associated with CNS aspergillosis. CNS aspergillosis was diagnosed and treated before death in only 1 patient. Patients in Group A received cytotoxic drugs, often had granulocytopenia, less commonly had focal neurological deficits, and seldom had seizures. Group B patients were not granulocytopenic, received no cytotoxic agents, underwent nontransplant surgery, and more frequently had focal neurological deficits. Eleven of the 17 patients (65%) had focal deficits, most of them hemiparesis. Meningeal signs were rare, but the cerebrospinal fluid was usually abnormal. The principal neuropathological process was Aspergillus invasion of blood vessels causing hemorrhagic infarction. Focal clinical deficits correlated neuroanatomically with Aspergillus lesions. In 2 patients, such lesions were detected by 99mTc‐DTPA or cerebral angiography before computed tomographic scanning. The lungs were the usual portal of entry, but isolated CNS lesions occurred in 2 patients. CNS aspergillosis should be considered as a cause of new onset of focal neurological deficits in patients with illnesses that are more diverse than has generally been appreciated.
The inferior longitudinal fasciculus: A reexamination in humans and monkeys
Authors: Tusa Ronald J. , Ungerleider Leslie G.
Published: January 2005

The inferior longitudinal fasciculus is commonly considered to be a long association fiber bundle interconnecting the occipital and temporal lobes. Based on blunt dissections of human and monkey brains, we have found that the only long fiber bundle common to both the occipital and temporal lobes is the geniculostriate pathway (i.e., optic radiations), located within the external sagittal stratum. In addition, our autoradiographic experiments indicate that the pathway from the occipital to the temporal cortex in monkeys consists of a series of U fibers that course beneath the cortical mantle to connect adjacent regions in striate, prestriate, and inferior temporal cortex. We suggest that the occipital and temporal lobes in human beings are similarly connected by a series of U fibers and that the term inferior longitudinal fasciculus be replaced with the term occipitotemporal projection system. Different clinical syndromes attributed to lesions of the inferior longitudinal fasciculus, including visual agnosia, prosopagnosia, and impaired visual recent memory, are probably due to interruption of fibers at different points along this projection system.
Biotinidase deficiency: Initial clinical features and rapid diagnosis
Authors: Wolf Barry , Heard Gregory S. , Weissbecker Karen A. , McVoy Julie R. Secor , Grier Robert E. , Leshner Robert T.
Published: January 2005

Biotinidase deficiency is the primary defect in most individuals with late‐onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.
Positron emission tomographic measurement of blood‐to‐brain and blood‐to‐tumor transport of 82Rb: The effect of dexamethasone and whole‐brain radiation therapy
Authors: Jarden Jens O. , Dhawan Vijay , Poltorak Alexander , Posner Jerome B. , Rottenberg David A.
Published: January 2005

Unidirectional blood‐to‐brain and blood‐to‐tumor transport rate constants for rubidium 82 were determined using dynamic positron emission tomography in patients with primary or metastatic brain tumors. Regional influx rate constants (K1) and plasma water volume (Vp) were estimated from the time course of blood and brain radioactivity following a bolus injection of tracer. Eight patients were studied before and 24 to 72 hours after treatment using pharmacological doses of dexamethasone, and 6 additional patients with metastatic brain tumors were studied before and within 60 to 90 minutes after 200‐ to 600‐rad whole‐brain radiation therapy. Steroid treatment was associated with a 9 to 48% decrease in tumor K1 and a 21% mean decrease in tumor Vp. No consistent changes in K1 or Vp were observed in control brain regions. Tumor K1 and Vp did not increase in patients undergoing whole‐brain radiation therapy, all of whom were taking dexamethasone at the time of study. These data suggest that corticosteroids decrease the permeability of tumor capillaries to small hydrophilic molecules (including those of some chemotherapeutic agents) and that steroid pretreatment prevents acute, and potentially dangerous, increases in tumor capillary permeability following cranial irradiation.
Transient global amnesia: A case‐control study
Authors: Kushner Michael J. , Hauser W. Allenn
Published: January 2005

The clinical findings and laboratory results from 18 patients with clear‐cut transient global amnesia (TGA) were compared with the results from 90 nonischemic neurological control patients using case‐control analysis. A prior episode of cerebral ischemia, generally in the posterior circulation, was the most significant risk factor for TGA. Other risk factors for cerebrovascular disease were more prominent in the TGA group, but this association became less significant when cerebral ischemia was controlled for. Migraine, epilepsy, and psychiatric disorders were not significantly associated with TGA. In 5 of 13 patients, computed tomography showed focal thalamic and temporal lobe abnormalities. The recurrence rate was 7.0% for both TGA and subsequent cerebral ischemia. We conclude that TGA is closely linked to cerebrovascular disease. Further, prior damage to anatomical structures critical to memory may be necessary for the expression of this syndrome.
Effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow and histopathology after middle cerebral artery occlusion
Authors: Mohamed A. A. , Gotoh O. , Graham D. I. , Osborne K. A. , McCulloch J. , Mendelow A. D. , Teasdale G. M. , Harper A. M.
Published: January 2005

We used the [14C]iodoantipyrine autoradiography technique to study the effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow (1CBF) in rats that underwent middle cerebral artery (MCA) occlusion. In untreated control animals there were profound localized reductions in 1CBF 30 minutes after MCA occlusion. These were most pronounced in neocortical areas and in the caudate nucleus ipsilateral to the MCA occlusion. In animals pretreated with nimodipine (1 μg · kg−1 · min−1 for 30 minutes before and 30 minutes after MCA occlusion), the ipsilateral decrease in 1CBF in cortical regions was significantly less than that in control animals. The drug did not appear to alter 1CBF in the ipsilateral caudate nucleus. Neuropathological quantification of the ischemic damage present 3 hours after occlusion showed thai: nimodipine pretreatment reduced the volume and extent of cellular damage in the periphery but not in the core of the lesion.
Vasoactive drugs produce selective changes in flow to experimental brain tumors
Authors: Panther Lori A. , Baumbach Gary L. , Bigner Darell D. , Piegors Donald , Groothuis Dennis R. , Heistad Donald D.
Published: January 2005

Most vasoactive drugs do not readily penetrate the blood‐brain barrier and do not affect cerebral blood flow. We tested the hypothesis that vasoactive drugs may alter blood flow to brain tumors in which the blood‐brain barrier is abnormal. Blood flow was measured with microspheres in dogs with brain tumors induced by avian sarcoma virus. Intravenously administered adenosine increased blood flow to tumor more than twofold but did not alter flow to normal brain. Intravenously administered norepinephrine decreased blood flow to tumor but not to normal brain. Thus, vasoactive drugs, which have little effect on blood flow to normal cerebrum, produce large changes in blood flow to brain tumors. We also examined responses to systemic hypercapnia. Hypercapnia increased blood flow to normal cerebrum more than twofold but failed to increase flow to tumors. Impaired vasodilator responses to hypercapnia in brain tumors, which cannot be explained primarily by an abnormality of the blood‐brain barrier, probably reflect another fundamental difference between vessels in normal brain and brain tumors. The finding that vasoactive drugs have selective effects on blood flow to brain tumors has important implications for delivery of lipid‐soluble chemotherapeutic drugs to the tumors.
Conduction failure and nerve conduction slowing in experimental allergic neuritis induced by P2‐specific T‐cell lines
Authors: Heininger Kurt , Stoll Guido , Linington Christopher , Toyka Klaus V. , Wekerle Hartmut
Published: January 2005

P2‐specific T cells (LiP2/A) mediate experimental allergic neuritis (EAN) in the Lewis rat after adoptive transfer to naive recipients. After a latent period of 4 days, injection of 2 × 106 line cells induced fulminant paraplegia and complete conduction failure in the peripheral nerves and roots, resembling acute axonal breakdown. Injection with 106 cells caused milder clinical signs, nerve conduction failure, and conduction slowing. Clinical and electrophysiological recovery from adoptively transferred EAN was nearly complete and its time course was inversely correlated to the initial severity of EAN. These findings suggest that EAN induced by the P2‐specific T‐cell line can lead to a profound and rapidly evolving nerve dysfunction in a dose‐dependent fashion.
Opening the blood–brain and blood–tumor barriers in experimental rat brain tumors: The effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow
Authors: Hiesiger E. M. , Voorhies R. M. , Basler G. A. , Lipschutz L. E. , Posner J. B. , Shapiro W. R.
Published: January 2005

Using quantitative autoradiography, we investigated the effect of intracarotid infusions of hyperosmolar mannitol solutions on capillary permeability and blood flow. Capillary permeability, expressed in terms of a blood‐to‐tissue transfer constant (K), was determined in two rat brain tumor models by measuring the entry of 14C‐alpha aminoisobutyric acid into brian tumor, into brain tissue adjacent to tumor, and into cortex. Cerebral blood flow was determined by measuring the uptake of 14C‐iodoantipyrine in one rat brain tumor model. Blood flow was examined in the same regions as K, as well as in the corpus callosum. Before mannitol administration, K values in both Walker 256 (W256) carcinosarcoma and C6 gliomas were much higher than those in cortex. C6 gliomas were about three times more permeable than were W256 tumors. There was a direct correlation between tumor size and increased capillary permeability. Mannitol at a concentration of 1.37 M did not increase the K values for either tumor or adjacent tissue. At 1.6 M, mannitol increased the K values for both tumors (1.7‐fold in C6 glioma and 13‐fold in W256) as well as for adjacent tissue. At both concentrations, mannitol markedly increased cortical K values in all groups: by 48‐to 72‐fold at 1.37 M and by 90‐ to 105‐fold at 1.6 M. The net effect of the mannitol was to reverse the tumor‐to‐cortex permeability relationship. Cortical blood flow increased modestly after intracarotid mannitol administration on both sides of the brain. These data provide little justification for using intracarotid mannitol during chemotherapy of human brain tumors.
A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study
Authors: Brun A. , Englund E.
Published: January 2005

In cases of Alzheimer's presenile and senile dementia, Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT), respectively, we have observed, in addition to the gray matter degeneration, a lesion that has the character of an incomplete infarction confined to the white matter. It is encountered in 60% of both groups, with mild changes in two thirds and moderate or severe changes in one third. It involves the deep white matter symmetrically, tapering off toward the cortex. It is characterized by partial loss of myelin, axons, and oligodendroglial cells; mild reactive astrocytic gliosis; and sparsely distributed macrophages as well as stenosis resulting from hyaline fibrosis of arterioles and smaller vessels. No complete or cavitating infarctions and no hypertensive vascular changes were observed. The white matter changes are thought to be due to hypoperfusion of the concerned white matter territories since, in addition to the white matter hyaline vascular stenosis, these cases show signs of cardiovascular disease, usually with hypotension.

The white matter disorder also occurs independent of the gray matter process of AD and SDAT and may be seen as the sole brain lesion in non‐AD subjects. Its occurrence is thus neither regularly related to the severity nor to the regional appearance and accentuation of the cortical Alzheimer process and is thus not likely to be just the result of a wallerian degeneration. Histologically it is similar in several respects to Binswanger's disease, although with some distinct differences. It is thus related to the cerebrovascular group of disorders in addition to AD and SDAT. In view of its frequency and severity, this white matter lesion is important to define, to diagnose, and ultimately to prevent or cure.
Swallowing and speech production in Parkinson's disease
Authors: Robbins Jo Anne , Logemann Jerilyn A. , Kirshner Howard S.
Published: January 2005

Videofluoroscopy was used to examine movement patterns during swallowing and speech production in 6 parkinsonian subjects and 6 age‐matched controls. Motility patterns for liquid and semisolid swallows were documented. We performed temporospatial analyses of oropharyngeal structures, particularly the velum, which is prominently involved in both motor speech production and swallowing. Differences were found between groups and conditions. All of the parkinsonian subjects exhibited abnormal oropharyngeal movement patterns and timing during the volitional oral as well as the pharyngeal stage of swallowing; only 50% of these subjects admitted to any swallowing difficulty upon questioning. Two of the subjects with Parkinson's disease aspirated liquids. Duration of velar movement during speech production significantly differentiated the groups (p < 0.01), reflecting reduced range of velar motion. Our findings suggest that rigidity and bradykinesia underlie the volitional speech abnormality as well as the disordered oral and pharyngeal stages of swallowing. Findings indicate that parkinsonian patients may be “silent aspirators” with decreased cough reflexes and lack of awareness of aspiration. The clinical value of videofluoroscopic monitoring of swallowing is that aspiration may be detected and managed early.
Human autonomy and the frontal lobes. Part II: Patient behavior in complex and social situations: The “environmental dependency syndrome”
Authors: Lhermitte F.
Published: January 2005

Imitation and utilization behavior have previously been described in terms of a simple interaction between an examiner and a patient, and were interpreted as an excessive dependence on environmental cues. In this study, patient dependence was observed in complex situations of everyday life. Two patients with focal unilateral frontal lobe lesions were observed while in a doctor's office, a lecture room, a car, and a garden, while visiting an apartment where various activities were possible, and while in a gift shop. The patients' behavior was striking, as though implicit in the environment was an order to respond to the situation in which they found themselves. The term environmental dependency syndrome is proposed for this condition. It implies a disorder in personal autonomy. Individual psychological traits influenced the way in which loss of autonomy was manifested. This study does not offer a physiological model of autonomy, but it does provide clinical and behavioral observations on the loss of autonomy secondary to unilateral lesions of the frontal lobe.
Dopamine denervation does not alter in vivo 3H‐spiperone binding in rat striatum: Implications for external imaging of dopamine receptors in Parkinson's disease
Authors: Bennett James P. , Wooten G. Frederick
Published: January 2005

Striatal particulate preparations, both from rats with lesion‐induced striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3H‐neuroleptic binding, which is interpreted to be the mechanism of denervation‐induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3H‐spiperone (3H‐SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate‐bound 3H‐SP in dopamine‐denervated compared with intact striata. 3H‐SP in vivo binds to less than 10% of striatal sites labeled by 3H‐SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3H‐SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3H‐SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3H‐SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo–administered 3H‐SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo.
Giant axonal neuropathy: Central abnormalities demonstrated by evoked potentials
Authors: Majnemer Annette , Rosenblatt Bernard , Watters Gordon , Andermann Frederick
Published: January 2005

Previous studies of giant axonal neuropathy have reported clinical and pathological findings that indicate involvement of the central nervous system. We studied 3 boys with giant axonal neuropathy, who were 14 to 16 years of age, using auditory, visual, and somatosensory evoked potentials. Absence of waveforms and prolongation of peak and interwave latencies were found. Abnormalities were noted in all modalities. The auditory brainstem evoked response in particular indicated a significant increase in brainstem conduction time. These studies add clinical neurophysiological confirmation of the central nervous system involvement in this disorder and may also provide a means of quantitative evaluation of its progression.
The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia
Authors: Dyck Peter James , Karnes Jeannine L. , O'Brien Peter , Okazaki Haruo , Lais Alfred , Engelstad JaNean
Published: January 2005

Characterization and quantitation of the spatial distribution of pathological abnormalities along the length of nerves may be helpful in understanding the underlying mechanisms of diabetic polyneuropathy. To this end, by examining transverse sections of nerve roots and proximal‐to‐distal levels of lower limb nerves in 9 controls and 15 diabetic patients with polyneuropathy, we have determined the myelinated fiber (MF) number, size distribution, median diameter, and variability of density (MFs/mm2) among frames and among fascicles. Even in cases with mild polyneuropathy, fiber loss, a decrrease in the median diameter, and an increase in the variability of density among frames and among fascicles began in proximal nerve and extended to distal levels. Multifocal fiber loss along the length of nerves and sprouting provide the best explanation for these findings. The pattern is dissimilar from that observed in diffuse metabolic disease of Schwann cells, neuronal degeneration, and dying‐back neuropathy, but like that found in experimental ischemic neuropathy induced by embolization of nerve capillaries.