bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease
Authors: Mouradian M. Maral , Heuser Isabella J. E. , Baronti Fabio , Chase Thomas N.
Published: January 2005

The management of fluctuations in motor function complicating advanced Parkinson's disease with continuously administered dopaminomimetics was studied in 12 patients. In response to 7 to 12 days of round‐the‐clock intravenous infusions of levodopa, fluctuations in motor performance gradually diminished, ultimately by more than 40°. The beneficial effect persisted for about 6 days after withdrawal of continuous parenteral treatment and resumption of standard oral therapy. Clinical improvement was associated with changes in several pharmacological indices: Acute dose‐response studies of intravenous levodopa showed a shift of the curve to the right in the immediate postinfusion phase compared to preinfusion studies; the therapeutic index improved significantly as patients demonstrated about 76° increased beneficial antiparkinsonian response with an equal degree of toxic dyskinetic effects; and the duration of action levodopa was prolonged by 30°. These results suggest that changes in central dopaminergic mechanisms contributing to motor complications in advanced Parkinson's disease can be modified by procedures that provide continuous dopamine replacement. Presumably these modifications underlie the gradual amelioration of motor fluctuations over several days of round‐the‐clock therapy. Results of the present study also suggest potential deleterious effects of chronic intermittent oral treatment in the development of motor complications and thus support the role of long‐term, continuous administration of dopaminomimetics.
Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord
Authors: Giulian Dana , Robertson Claudia
Published: January 2005

Transient ischemia to the lumbar and sacral sections of the spinal cord of rabbit leads to a deterioration in neurological function that usually worsens 24 to 48 hours after injury. This decline in movement of the hindlimbs develops simultaneously with the appearance of mononuclear phagocytes in the gray matter of injured neural tissue. Chloroquine and colchicine inhibit phagocytic and secretory functions in mononuclear phagocytes. When given up to 6 hours after an induced ischemic lesion in rabbit, this drug combination decreased the number of mononuclear phagocytes found within the gray matter of damaged spinal cord, improved the recovery of function of the hindlimbs and bladder, preserved spinal somatosensory evoked potentials, and promoted the survival of motor neurons. In contrast, the glucocorticoid dexamethasone, a weak inhibitor of mononuclear phagocytes in vivo, did not reduce the number of inflammatory cells in the spinal cord and did not improve motor and bladder functions. The suppression of mononuclear phagocytes soon after ischemic injury may offer a new approach in the treatment of vascular disease in the central nervous system.
Antimyelin basic protein and antimyelin antibody‐producing cells in multiple sclerosis
Authors: Olsson Tomas , Baig Shahid , Jeberg Bo Hö , Link Hans
Published: January 2005

The B‐Cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty‐seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 104 mononuclear cells, respectively. Total numbers of IgG‐producing cells occurred at a mean number of 75 per 104 CSF Cells. Cells producing antimyelin or anti–myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG‐producing cells. A pronounced B‐cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.
Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis
Authors: Murayama Shigeo , Mori Hiroshi , Ihara Yasuo , Bouldin Thomas W. , Suzuki Kinuko , Tomonaga Masanori
Published: January 2005

Neuronal inclusions in lower motor neurons in 23 cases of adult‐onset sporadic amyotrophic lateral sclerosis were studied immunocytochemically and ultrastructurally. Monoclonal and polyclonal antiubiquitin antibodies recognized four structures in the neuronal perikarya: (1) all Lewy body–like inclusions in 6 cases with a relatively short clinical course, (2) a small percentage of Bunina bodies in 4 cases with abundant Bunina bodies, (3) ill‐defined structures closely associated with Bunina bodies (Bunina body–related structures) in 15 cases, and (4) a focally aggregated meshwork of fine filamentous structures not associated with Bunina bodies in all cases. These four structures were not recognized by the antibodies raised against cytoskeletal proteins (neurofilament, tubulin, microtubule‐associated protein 2, and phosphorylated tau). Electron microscopy revealed Lewy body–like inclusions to be accumulations of randomly oriented filaments, approximately 15 nm in diameter, covered by fine granules. Bundles of coated filaments 12 nm in diameter that sometimes formed Bunina body–like structures were also observed in the perikarya. Immunoelectron microscopy showed the reaction product with antiubiquitin to be on the filaments, 15 nm in diameter, of Lewy body–like inclusions. Our study revealed the existence of two types of filaments in lower motor neurons of patients with amyotrophic lateral sclerosis: (1) ubiquitin‐positive, granule‐associated filaments, approximately 15 nm in diameter, that form Lewy body–like inclusions; and (2) 12 nm coated filaments that may be a candidate for another ubiquitin‐positive structure and possibly a precursor of Bunina bodies. These two types of filaments may represent early pathological changes of lower motor neurons in amyotrophic lateral sclerosis.
A disorder of axonal development, necrotizing myopathy, cardiomyopathy, and cataracts: A new familial disease
Authors: Lyon Gilles , Arita Fernando , Le Galloudec Eric , Vallée Louis , Mission Jean‐Paul , Ferrière Gérard
Published: January 2005

We report severe congenital encephalopathy and profound hypotonia associated with necrotizing myopathy, cardiomyopathy, and cataracts in 3 infants, including 2 sisters. Brain scans suggested agenesis of the corpus callosum. Neuropathological findings consisted of severe atrophy of the corpus callosum (not the usual agenesis with longitudinal callosal bundles), atrophy of the white matter, and absence of pyramidal tracts in the medulla. Multiple axonal swellings were present in the white matter and in Purkinje Cells. Except for the corpus subthalamicum, gray matter structures were preserved. These findings are considered to be the expression of a primary disorder of axonal development leading to a reduction in interneuronal synaptic contacts. It is suggested that the anomaly may be due to an extension of the normal phenomenon of axonal elimination, related to a primary defect of the axonal cytoskeleton. The concept of a primary axonal disorder may also apply to other, mostly familial, conditions with progressive atrophy of the cerebral white matter and corpus callosum.
Delineation of single‐word semantic comprehension deficits in aphasia, with anatomical correlation
Authors: Hart John , Gordon Barry
Published: January 2005

In 3 of 18 aphasic patients pure deficits in semantic comprehension at the single‐word level were defined through a series of tasks that excluded possible confounding deficits in auditory perception, visual perception, or speech production. In these pure cases, deficits were found at the superordinate, equivalence, and subordinate levels of single‐word semantic processing. Pure semantic deficits were found to be correlated with damage to the left posterior temporal and inferior parietal region; patients whose damage spared this area did not evince such deficits, and the converse was also true. This study confirms the existence of separable deficits in semantic comprehension and points conclusively to the left posterior temporal and inferior parietal region as being critical for semantic processing. This anatomical localization is in keeping with anatomical studies from nonhuman primates, suggesting that these regions may be concerned with multimodal processing and integration of language.
A large kindred with autosomal dominant Parkinson's disease
Authors: Golbe Lawrence I. , Di Iorio Giuseppe , Bonavita Vincenzo , Miller Douglas C. , Duvoisin Roger C.
Published: January 2005

We report two large kindreds with Parkinson's disease (PD) apparently inherited in autosomal dominant fashion. Forty‐one persons in four generations have been affected; we have examined 7 of them. The two kindreds originated in a single small town in southern Italy and therefore are probably related. The illness was typical for PD except for early onset at a mean age of 46.5 years and a rapid course that averaged 9.7 years from onset to death. Clinical appearance and response to levodopa were typical for PD. Only one instance of difinite nonpenetrance is known. Autopsy of 2 patients in one kindred showed the pathological changes typical of PD with Lewy bodies. Disease duration among affected persons who spent most of their lives in Italy was longer than for their affected US relatives, suggesting that exogenous agents may influence the course of this genetic illness. We conclude that what is probably a single gene without an additional environmental insult can cause the pathological changes typical of PD. Our findings therefore enhance the likelihood of significant genetic component in the cause of sporadic PD. By identifying a toxic gene product, future molecular genetic studies in our kindred(s) may provide insight into the pathogenesis of sporadic PD.
Detection of epileptiform activity by different noninvasive EEG methods in complex partial epilepsy
Authors: Goodin Douglas S. , Aminoff Michael J. , Laxer Kenneth D.
Published: January 2005

The diagnostic utility of different noninvasive electrode placements for deriving the electroencephalogram and detecting interictal epileptiform discharges was compared. Anterior temporal and nasopharyngeal electrodes in combination with routine scalp electrodes detected over 97% of the spikes, whereas recording from only standard electrode placements detected 58%. Minisphenoidal and surface sphenoidal electrodes were generally not helpful. In some circumstances, however, the use of surface sphenoidal electrodes provided important confirmatory information. In no case did the minisphenoidal electrodes provide unique information, and their use seems unjustified, although the inclusion of other nonstandard electrodes in the recording montage is important to increase the yield.
Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism‐dementia complex on guam in comparison with those in Parkinson's and Alzheimer's diseases
Authors: Goto Satoshi , Hirano Asao , Matsumoto Sadayuki
Published: January 2005

A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism‐dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine‐enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism‐dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism‐dementia complex showed severe reduction (> 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico‐subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism‐dementia complex on Guam.
Successful chemotherapy for newly diagnosed aggressive oligodendroglioma
Authors: Macdonald David R. , Gaspar Laurie E. , Cairncross J. Gregory
Published: January 2005

We treated 3 patients with newly diagnosed aggressive oligodendroglioma with chemotherapy prior to radiotherapy and observed responses. All had residual or progressive tumor following initial surgery. We used a combination called PCV‐3 because recurrent anaplastic oligodendroglioma responds predictably to this regimen. Chemotherapy for response induction followed by radiotherapy for consolidation is feasible and effective initial treatment for this tumor.
Dominantly transmitted congenital indifference to pain
Authors: Landrieu P. , Said G. , Allaire C.
Published: January 2005

Two patients from a family with dominantly inherited indifference to pain were investigated. Perception of the other sensory modalities was normal as was the remainder of the neurological examination. Electrophysiological studies and morphometric evaluation of myelinated and unmyelinated fibers of nerve biopsy specimens were normal. This is the first morphometric study of peripheral nerve in dominantly inherited indifference to pain.
Cholinergic deficiency and frontal dysfunction in Parkinson's disease
Authors: Dubois Bruno , Pillon Bernard , Lhermitte Françlois , Agid Yves
Published: January 2005

To investigate the influence of Central cholinergic deficit on cognitive function in Parkinson's disease (PD), we compared the neuropsychological performance of a group of 20 patients who were treated with anticholinergic drugs (mean daily dose, 10.2mg) with that of a group of 20 patients who received no anticholinergics. The two groups were matched for all the variables of parkinsonism and levodopa therapy. At the dose used, there was no significant difference between the two groups of patients for intellectual, visuospatial, instrumental, and memory function. In contrast, in the group that received anticholinergics severe impairment was observed on tests believed to assess frontal lobe function. These results suggest that the lesion of the ascending cholinergic neurons, which has been demonstrated post mortem in PD, may play a role in the subcorticofrontal behavioral impairment of this disease.
Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome
Authors: Kushner Michael , Nencini Patrizia , Reivich Martin , Rango Mario , Jamieson Dara , Fazekas Franz , Zimmerman Robert , Chawluk John , Alavi Abass , Alves Wayne
Published: January 2005

We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F‐fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p < 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p < 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p < 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus.
Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo‐obstruction: POLIP syndrome
Authors: Simon Lynn T. , Horoupian Dikran S. , Dorfman Leslie J. , Marks Michael , Herrick Maie Kaarsoo , Wasserstein Philip , Smith Marion E.
Published: January 2005

We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external opthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo‐obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, opthalmoplegia, leukoencephalopathy, and intestinal pseudo‐obstruction.
Synaptic transmission in human neocortex removed for treatment of intractable epilepsy in children
Authors: Wuarin Jean‐Pierre , Kim Yang In , Cepeda Carlos , Tasker Jeffrey G. , Walsh John P. , Peacock Warwick J. , Buchwald Nathaniel A. , Dudek F. Edward
Published: January 2005

Synaptic transmission to pyramidal cells was studied in slices of neocortex resected from infants and children (n = 10, age 8 months to 13 years) undergoing surgical treatment for intractable epilepsy. Most specimens were from the least abnormal area of the resection. Stable intracellular recordings could be obtained for up to 8 hours. Most of the recorded neurons had electrophysiological characteristics similar to those of regular‐firing pyramidal cells and were in layers III to V, which was confirmed by intracellular staining with Lucifer yellow. Local extracellular stimulation evoked a sequence of excitatory and inhibitory postsynaptic potentials. Kynurenic acid, a broad‐spectrum excitatory amino acid antagonist, depressed the evoked excitatory postsynaptic potential. After application of the gamma‐aminobutyric acid antagonist, bicuculline (10–30 μM), extracellular stimulation induced large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous bursts occasionally occured in bicuculline. This effect of bicuculline was observed in all the tissue samples, even those from infant patients (n = 4, age 8–16 months). Kynurenic acid depressed or abolished both spontaneous and stimulation‐induced bursts. The competitive antagonist for N‐methyl‐D‐aspartate receptors, DL‐2‐amino‐5‐phosphonopentanoic acid decreased the duration of bicuculline‐induced bursts. These data provide evidence that, similar to rat and cat neocortex, excitatory and inhibitory amino acids are important transmitters to pyramidal cells in immature human neocortex.
Quadriceps myopathy: Forme fruste of Becker muscular dystrophy
Authors: Sunohara Nobuhiko , Arahata Kiichi , Hoffman Eric P. , Yamada Hitoshi , Nishimiya Jin , Arikawa Eri , Kaido Misako , Nonaka Ikuya , Sugita Hideo
Published: January 2005

We examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles. All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as “patchy” or discontinuous immunostaining at the surface membrane of the muscle fibers. One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy. We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy.
A follow‐up study of intractable seizures in childhood
Authors: Huttenlocher Peter R. , Hapke Ronald J.
Published: January 2005

One hundred forty‐five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset. The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age. Age of onset was significantly later (mean 5.0 ± 0.5 yr [SEM]) in the group of children with borderline to normal intelligence. Follow‐up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year. Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation. Seizure type had some effects on outcome. Children with focal atrophic brain lesions did no worse than those without definable pathology on brain‐imaging studies.
Extended levodopa release from a subcutaneously implanted polymer matrix in rats
Authors: Sabel B. A. , Dominiak P. , Häuser W. , During M. J. , Freese A.
Published: January 2005

It is well recognized that plasma fluctuations resulting from oral levodopa therapy may cause an unstable clinical response in parkinsonian patients. We have therefore developed a slow‐release polymer matrix system that can deliver levodopa continuously for extended periods of time (at least 225 days) after subcutaneous implantation in rats. Advantages of this approach include (1) the elimination of levodopa plasma fluctuations and (2) the possibility of reducing the required dose due to constant plasma levels and because the gastrointestinal tract is circumvented. The peripheral implantation of polymer systems containing levodopa, dopamine receptor agonists, or other anti‐Parkinson agents may constitute a novel technology of drug delivery to improve the care of patients with Parkinson's disease.
Developmental dyslexia in women: Neuropathological findings in three patients
Authors: Humphreys Peter , Kaufmann Walter E. , Galaburda Albert M.
Published: January 2005

Brains from male cases with dyslexia show symmetry of the planum temporale and predominantly left‐sided cerebrocortical microdysgenesis. We now report on three women with dyslexia. In all brains, the planum temporale was again symmetrical. Also, in two of the brains, multiple foci of cerebrocortical glial scarring were present. In both women, many of the scars were myelinated, suggesting origination during late intrauterine or early postnatal life. In one, scars were mainly left perisylvian and involved portions of the vascular border zone of the temporal cortex. In the other, scars were more numerous and occurred in the border zone of the anterior, middle, and posterior cerebral arteries symmetrically. All three cases showed to a variable extent brain warts, molecular layer ectopias, and focal architectonic dysplasia identical to those seen in the male cases. Two women had primary brain neoplasms, an oligodendroglioma and a low‐grade astrocytoma, respectively, and two women showed small angiomas. Reexamination of previously reported male cases disclosed one with myelinated glial scars. Two control brains with asymmetrical plana temporale showed myelinated glial scars as well. The significance of the anatomical findings is discussed, and possible etiological factors are considered with known effects of autoimmune diseases on the nervous system.
Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography
Authors: Gilman Sid , Junck Larry , Markel Dorene S. , Koeppe Robert A. , Kluin Karen J.
Published: January 2005

Local cerebral metabolic rate for glucose was studied with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age‐matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedrich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.
General assay for phosphoproteins in cerebrospinal fluid: A candidate market for paraneoplastic cerebellar degeneration
Authors: Gandy Samuel E. , Grebb Jack A. , Rosen Neal , Albert Katherine A. , Devinsky Orrin , Blumberg Hilary , Anderson Neil , Cedarbaum Jesse M. , Porter Roger J. , Sedvall Göran , Posner Jerome B. , Greengard Paul
Published: January 2005

The components of protein phosphorylation systems (protein kinases, protein phosphatases, and their phosphoprotein substrates) are highly enriched in neuronal cells compared with other cell types. We exploited this relative neuronal enrichment of protein phosphorylation system components to develop a general assay technique for putative protein kinase substrates (phosphoproteins) in human cerebrospinal fluid. Using this cerebrospinal fluid phosphoprotein assay, we have detected a putative protein kinase C substrate protein of apparent Mr 60 kd in 6 of 14 patients with paraneoplastic cerebellar degeneration but not in any of 55 patients with a variety of other neurological diseases. Phosphoproteins in cerebrospinal fluid may provide novel and unique markers for the diagnosis or staging of neuronal diseases as well as offer potential insights into the biochemical characterization of affected neuronal populations.
OKT3 encephalopathy
Authors: Coleman Anton E. , Norman Douglas J.
Published: January 2005

OKT3 therapy for induction immunosuppression in a patient who underwent renal transplantation produced obtundation and quadriparesis associated with computed tomographic scan evidence of brain edema. These findings resolved over 3 days with supportive therapy and OKT3 withdrawal.
Nerve growth factor prevents toxic neuropathy in mice
Authors: Apfel Stuart C. , Lipton Richard B. , Arezzo Joseph C. , Kessler John A.
Published: January 2005

Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy. Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor. We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo. Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve. Coadministration of nerve growth factor prevented all of these sings of neurotoxicity. These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies.
Capillary prolactin measurement for diagnosis of seizures
Authors: Fisher Robert S. , Chan Daniel W. , Bare Mary , Lesser Ronald P.
Published: January 2005

Measurement of serum prolactin levels can be useful in the diagnosis of epilepsy, since prolactin levels often rise after seizures, but not after most imitators of epilepsy. Utility of the test is limited by the need to obtain blood 10 to 20 minutes after the episode. The present study documents the validity of prolactin measurements using capillary blood, which was obtained by the finger‐stick method after a possible seizure and then applied to filter paper. Venous and capillary prolactin levels were determined 10 to 20 minutes after seizure‐like episodes in 20 patients who were studied in an epilepsy monitoring unit. Venous and capillary prolactin values correlated, with a Pearson coefficient of 0.90. Using a criteria of any elevation above the laboratory upper limit of normal, capillary prolactin values correctly identified seizure versus pseudoseizure in 9 (100%) of 9 patients with generalized tonic‐clonic seizures, in 5 (71%) of 7 patients with complex partial seizures, and 4 (100%) of 4 patients with pseudoseizures. Prolactin values were unaffected by leaving filter paper samples at room temperature for up to 1 week. This study suggests the utility of diagnostic capillary blood collection kits to assist in the diagnosis of epilepsy in outpatients.
JC virus detection by in situ hybridization in brain tissue from elderly patients
Authors: Mori Mayumi , Kurata Hirokazu , Tajima Masako , Shimada Hiroyuki
Published: January 2005

Brains from 10 patients aged 68 to 96 years at time of death were studied for JC viral DNA and common papovaviral capsid protein. In situ hybridization to JC viral DNA was performed by affinity cytochemistry using a biotinylated fragment of JC viral DNA. Immunohistochemistry was performed on brain tissue by the avidin DH‐biotinylated horseradish peroxidase technique using polyclonal antibody raised against the papovaviral capsid protein. Viral protein and DNA were detected in 4 of 10 patients. JC virus may be present in the brains of aged patients more frequently than previously suspected.
The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage
Authors: Rinkel Gabriel J. E. , Wijdicks Eelco F. M. , Vermeulen Marinus , Hasan Djo , Brouwers Paul J. A. M. , van Gijn Jan
Published: January 2005

We studied the early clinical course of 65 patients with perimesencephalic (nonaneurysmal) subarachnoid hemorrhage. None of the patients rebled; none had delayed cerebral ischemia; and only 3 patients (5%) developed clinical signs of acute hydrocephalus, 2 requiring ventricular shunting. Hyponatremia and electrocardiographic changes were found in the same proportions as in patients with aneurysmal rupture. All patients had a good outcome after 3 months. To control for the influence of the relatively small amount of cisternal blood in perimesencephalic hemorrhage on the absence of delayed cerebral ischemia, we compared these 65 patients with 49 patients who had aneurysmal subarachnoid hemorrhage. This control group with aneurysms was selected according to a similar amount of cisternal blood, a comparable level of consciousness on admission, and absence of other factors known to increase the risk for delayed cerebral ischemia. We found that 4 of the 49 patients with aneurysmal hemorrhage developed delayed cerebral ischemia (Fisher's exact test, p = 0.03); therefore the relatively small amount of blood does not account for the absence of delayed cerebral ischemia in perimesencephalic hemorrhage. Patients with a perimesencephalic pattern of hemorrhage and a normal angiogram should be considered to have a distinct subset of subarachnoid hemorrhage and should be excluded from future treatment trials of patients with subarachnoid hemorrhage.
Cold‐induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn‐Superoxide dismutase
Authors: Chan P. H. , Yang G. Y. , Chen S. F. , Carlson E. , Epstein C. J.
Published: January 2005

It has been proposed that oxygen‐derived radicals, superoxide in particular, are involved in the alteration of blood‐brain barrier permeability and the pathogenesis of brain edema following trauma, ischemia, and reperfusion injury. Using transgenic mice that overexpress the human gene for copper‐zinc‐superoxide dismutase, we studied the role of superoxide radicals in the blood‐brain permeability changes, edema development, and delayed infarction resulting from cold‐trauma brain injury. At 2 hours after a 30‐second cold injury, cerebral water and Evans blue contents were reduced, respectively, from 80 ± 0.2% and 132.7 ± 12.9 m̈g/gm of dry weight for nontransgenic mice to 78.5 ± 0.3% and 87.1 ± 9.9% m̈g/gm of dry weight for transgenic mice. Infarction, as measured by 2,3,5‐triphenyltetrazolium chloride staining, was reduced by 52% in transgenic brains. These data indicate that an increased level of superoxide dismutase activity in the brain reduces the development of vasogenic brain edema and infarction. Superoxide radicals play an important role in the pathogenesis of these lesions in cold‐traumatized brain.
Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy
Authors: McDonald John W. , Garofalo Elizabeth A. , Hood Terry , Sackellares J. Chris , Gilman Sid , McKeever Paul E. , Troncoso Juan C. , Johnston Michael V.
Published: January 2005

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N‐methyl‐D‐aspartate (NMDA), strychnine‐insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma‐aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age‐comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate‐type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.
Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease
Authors: Saper Clifford B. , Sorrentino Denise M. , German Dwight C. , Lacalle Sonsoles De
Published: January 2005

Parkinson's disease is thought ot cause degeneration of melanin‐pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation.
The European stroke prevention study (ESPS): Results by arterial distribution
Authors: Sivenius Juhani , Riekkinen Paavo J. , Smets Philippe , Laakso Markku , Lowenthal Armand
Published: January 2005

The European Stroke Prevention Study was a multicenter study comparing the effect of the combination of dipyridamole, 75 mg, and acetylsalicylic acid, 330 mg, three times a day, to that of placebo in 2,500 patients in the secondary prevention of stroke or death after one or more transient ischemic attacks, reversible ischemic neurological deficits, or strokes of antherothrombotic origin. The patients with vertebrobasilar events at entry comprised one‐third of the whole patient population. The overall total incidene of stroke or death (the end points) during the 2‐year follow‐up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women.
Strongly succinate dehydrogenase–reactive blood vessels in muscles from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes
Authors: Hasegawa Hitomi , Matsuoka Taro , Goto Yu‐ichi , Nonaka Ikuya
Published: January 2005

Intramuscular blood vessels were examined with succinate dehydrogenase stain in skeletal muscle biopsy specimens from 6 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Almost all arteries had large granular deposits with high succinate dehydrogenase activity in their walls. Electron microscopic examination of serial frozen sections of these biopsies showed that the smooth muscle cells of the strongly succinate dehydrogenase–reactive blood vessels contained markedly proliferated mitochondria, characteristic of patients with MELAS. The presence of strongly succinate dehydrogenase–reactive blood vessels in muscle biopsy specimens provides an important clue toward understanding the underlying pathogenetic mechanism in patients with MELAS as well as another approach to the diagnosis of this disorder.
Focal capsular vascular lesions can selectively deafferent the prerolandic or the parietal cortex: Somatosensory evoked potentials evidence
Authors: Mauguière François , Desmedt John E.
Published: January 2005

Four patients with a unilateral focal vascular accident involving the internal capsule (but not the cortex) were studied electrophysiologically. Averaged somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve on the left or the right side were analyzed. In the 3 patients with hemiparesis and normal somatic sensation, the precentral P22 and N30 SEP components were lost, whereas the parietal components were preserved. In another patient with clinical somatosensory loss unaccompanied by any central motor impairment, the precentral SEP components were preserved, whereas the parietal SEP components were lost. Thus, a small capsular lesion can eliminate distinct cortical SEP components by selectively involving either the axons of the thalamic VPLc nucleus going to parietal receiving cortex or the axons of thalamic VPLo going to motor area 4. These findings extend to subcortical lesions the diagnostic value of SEPS in patients with dissociated clinical motor and sensory signs.
The treatable dementia of sjögren's syndrome
Authors: Caselli Richard J. , Scheithauer Bernd W. , Bowles Carolyn A. , Trenerry Max R. , Meyer Fredric B. , Smigielski Jeffrey S. , Rodriguez Moses
Published: January 2005

Progressive dementia developed during a 15‐month period in a 56‐year‐old woman with serologically and clinically documented primary Sjögren's syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high‐dose corticosteroids produced rapid and nearly complete resolution of the dementia.
Platelet‐activating factor in stroke and brain injury
Authors: Lindsberg Perttu J. , Hallenbeck John M. , Feuerstein Giora
Published: January 2005

Platelet‐activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet‐activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet‐activating factor include disruption of the blood‐brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet‐activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet‐activating factor in experimental models of CNS inchemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet‐activating factor‐mediated effects and propose directions for future studies.
Control of cerebral circulation in the high‐risk Neonate
Authors: Pryds O.
Published: January 2005

A knowledge of neonatal cerebrovascular physiology is essential to the understanding of diseases that frequently affect the subsequent development of the newborn brain. Recent observations indicate that the cerebral vessels of the healthy newborn infant, even the very preterm, respond to physiological stimuli in the same manner as in the mature organism. Thus, cerebral blood flow changes with changes in arterial carbon dioxide tension (Paco2), oxygen concentration (Cao2), or glucose concentration, whereas cerebral blood flow remains constant at minor fluctuations in arterial blood pressure. In pathological states, pressure autoregulation may become impaired, and in severe cases the vessels do not react to chemical or metabolic stimuli. These infants are at high risk for developing cerebral lesions, and they may be candidates for new „brain‐protecting regimens”︁.
Discordance of T‐cell receptor β‐chain genes in familial multiple sclerosis
Authors: Lynch Sharon G. , Rose John W. , Petajan Jack H. , Stauffer Dora , Kamerath Craig , Leppert Mark
Published: January 2005

Restriction fragment length polymorphisms of the T‐cell receptor β‐chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty‐four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans. Linkage analysis was performed using the Bgl II and the KpnI polymorphisms. With penetrance values from 0.1 to 0.7, and altering the scoring of the normal individuals with abnormal findings on MRI scans from “unknown” to “affected,” log of the odds scores between −4.59 to −12.76 were found for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1.0, the LOD scores ranged from −8.20 to −32.98. These findings do not support a direct role of T‐cell receptor β‐chain gene in the inheritance of MS.
Abnormal dopamine uptake sites in postmortem striatum from patients with tourette's syndrome
Authors: Singer Harvey S. , Hahn In‐Hei , Moran Timothy H.
Published: January 2005

The dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre‐ and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites ([3H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High‐pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4‐dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors ([3H]SCH 23390 and [3H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3′,5′‐ monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We spéculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.
Is the carboxyl‐terminus of dystrophin required for membrane association? A novel, severe case of duchenne muscular dystrophy
Authors: Hoffman Eric P. , Garcia Carlos A. , Chamberlain Jeffrey S. , Angelini Corrado , Lupski James R. , Fenwick Raymond
Published: January 2005

Duchenne muscular dystrophy is a lethal X‐linked recessive disorder caused by the deficiency of a component of the muscle fiber membrane cytoskeleton called dystrophin. Becker muscular dystrophy, a clinically milder disorder, results from dystrophin abnormalities rather than deficiency. We identified the first patient who is clearly an exception to these established clinical and biochemical correlates. The patient described clinically had particularly severe Duchenne dystrophy. Biochemically, his muscle contained substantial amounts of abnormal dystrophin (Becker‐like). Characterization of the dystrophin protein and gene revealed a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl‐terminal domain. This patient's dystrophin seemed to have a deleterious “dominant” effect on his muscle: The presence of this abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been. This patient challenges the current hypothesis that dystrophin associates with the plasma membrane solely via its carboxyl‐terminus, yet supports the hypothesis that an intact carboxyl‐terminus is crucial for correct dystrophin function.