bluuebunny/crossref_metadata_2025 huggingface dataset:
Very long chain acyl‐coenzyme A dehydrogenase deficiency with adult onset
Authors: Smelt A. H. M. , Poorthuis B. J. H. M. , Onkenhout W. , Scholte H. R. , Andresen B. S. , van Duinen S. G. , Gregersen N. , Wintzen A. R.
Published: January 2005

Very long chain acyl‐coenzyme A (acyl‐CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial β‐oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified stongly elevated levels of tetradecenoic acid, 14:1(n‐9), tetradecadienoic acid, 14:2(n‐6), and hexadecadienoic acid, 16:2(n‐6). Palmitoyl‐CoA and behenoyl‐CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L‐carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis.
Fibroblast growth factor‐2/brain‐derived neurotrophic factor—associated maturation of new neurons generated from adult human subependymal cells
Authors: Pincus David W. , Keyoung H. Michael , Harrison‐Restelli Catherine , Goodman Robert R. , Fraser Richard A. R. , Edgar Mark , Sakakibara Shin‐Ichi , Okano Hideyuki , Nedergaard Maiken , Goldman Steven A.
Published: January 2005

The adult mammalian forebrain harbors neuronal precursor cells in the subependymal zone (SZ). Neuronal progenitors also persist in the adult human SZ and have been cultured from epileptic temporal lobe. In the present study, we sought to identify these neural progenitors in situ, and to direct their expansion and neuronal differentiation in vitro. We prepared explants of adult human SZ, obtained from temporal lobe resections of refractory epileptics. The resultant cultures were treated with fibroblast growth factor‐2 (FGF–2) for a week, with concurrent exposure to [3H] thymidine, then switched to media containing brain‐derived neurotrophic factor (BDNF) for up to 2 months. Sporadic neuronal outgrowth, verified antigenically and physiologically, was observed from SZ cultures regardless of FGF‐2/BDNF treatment; however, only FGF‐2/BDNF–treated cultures exhibited profuse outgrowth, and these displayed neuronal survival as long as 9 weeks in vitro. In addition, cortical cultures derived from two brains generated microtubule‐associated protein‐2+ neurons, which incorporated [3H]thymidine and exhibited significant calcium increments to depolarization. In histological sections of the subependyma, both uncommitted and restricted progenitors, defined respectively by musashi and Hu protein expression, were identified. Thus, the adult human subependyma harbors neural progenitors, which are able to give rise to neurons whose numbers can be supported for prolonged periods in vitro.
Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis
Authors: Aoki Masashi , Lin Chien‐Liang G. , Rothstein Jeffrey D. , Geller Brian A. , Hosler Besty A. , Munsat Theodore L. , Horvitz H. Robert , Brown Robert H.
Published: January 2005

Recently, variant mRNA transcripts for the astroglial glutamate transporter EAAT2 have been detected in brain tissues of 60% of patients with sporadic amyotrophic lateral sclerosis (SALS). We have tested the hypothesis that the gene for EAAT2 may be defective in some ALS cases. In 16 familial ALS (FALS) pedigrees without mutations in SODI, we failed to detect genetic linkage to the EAAT2 locus. We next characterized the genomic organization of the EAAT2 gene and used single‐strad conformation polymorphism analysis of genomic DNA to identify one novel mutation in a single SALS patient and two novel mutations in 2 affected FALS siblings. In the SALS patient, the mutation substitutes serine for an asparagine that might be involved in N‐linked glycosylation of the EAAT2 protein. In the 2 affected individuals in the FALS family, we detected both a mutation in the 5′ end of intron 7 and a silent G→A transition at codon 234 in exon 5. It remains unclear whether this intron 7 mutation is related to the defective mRNA splicing. These studies indicate that germline mutations in the EAAT2 gene are infrequent and do not explain the presence of variant mRNA transcripts of EAAT2 in more than one‐half of ALS cases.
Dejerine‐sottas neuropathy and PMP22 point mutations: A new base pair substitution and a possible “hot spot” on Ser72
Authors: Marques Wilson , Thomas P. K. , Sweeney Mary G. , Carr Lucinda , Wood Nicholas W.
Published: January 2005

The occurrence of mutations in peripheral myelin protein 22 is one of the genetic mechanisms associated with Dejerine‐Sottas neuropathy (DSN). On direct sequencing 2 of such patients we have found the first mutation in the third transmembrane domain associated with this neuropathy and the fourth Ser72Leu. We Propose that the Ser72 may be a “hot spot” for DSN and that this should be considered for molecular analysis.
Neurological manifestations of falciparum malaria
Authors: Newton Charles R. J. C. , Warrell David A.
Published: January 2005

Plasmodium falciparum remains one of the most common causes of central nervous system infection worldwide. Recently, differences between the pathophysiology of cerebral malaria in African children and nonimmune adults have been discovered, new syndromes occurring after malaria infection described, and mechanisms for the pathogenesis proposed. In addition, new antimalarial agents have been examined worldwide and initial studies on supportive studies conducted. This paper reviews these new advances, putting them into the perspective of the more established knowledge.
Serotonin inhibits trigeminal nucleus activity evoked by craniovascular stimulation through a 5ht 1b/1D receptor: A central action in migraine?
Authors: Goadsby Peter J. , Hoskin Karen L.
Published: January 2005

The development of serotonin (5HT1B/1D) agonists as treatments for the acute of migraine has resulted in considerable interest in their mechanism of action and, to some extent, renewed interest in the role of serotonin (5‐hydroxytrypatmine; 5HT) in the disorder. The initial synthesis of this class of compounds was predicated on the clinical observation that intravenous 5HT terminated acute attacks of migraine. In this study the superior sagittal sinus was isolated in the α‐chloralose (60mg/kg IP and 20 mg/kg IV injection supplementary 2 hourly) anesthetized cat. The sinus was stimulated electrically (120V, 250 °sec duration, 0.3 Hz), and neurons of the trigeminocervical complex in the dorsal C2 spinal cord were monitored using electrophysiological methods. After baseline recordings in each animal, 5HT (15 μg/kg/min) was infused for 5 minutes in the presence of either vehicle (group A) or the 5HT 1B/1D antagonist GR127935 (100 μg/kg IV injection; group B). The baseline probability of cell firing after sagittal sinus stimulation was 0.61 ± 0.1 at a latency to the fastest peak of 11.1 ± 0.4 msec. In group A, 5HT infusion alone had a small effect of increasing mean blood pressure (12 ± 3 mm Hg), which in itself did not alter cell firing. In group A, 5HT alone had an inhibitory effect on evoked trigeminal activity, which developed 15 to 20 minutes after commencement of the infusion. The inhibition of cell firing lasted for 20 minutes, after which the activity returned to baseline. In group B, the combination of 5HT and GRI127935 had no effect on trigeminal cell firing, although the small hypertensive effect was still present. These data indicate that 5HT inhibits evoked trigeminal nucleus firing via the 5HT 1B/1D receptor at which GRI127935 is an antagonist. It is likely that some part of the effect of 5HT in migraine relates to inhibition of trigeminal nucleus activity, just as it is likely that some part of the effect of the triptans is also mediated at this central site and may be complementary to their nonneuronal actions. Moreover, the data highlight the case for describing this class of headache as neurovascular headaches rather than vascular headaches, to recognize the implicit contribution of the trigeminovascular system to their pathophysiology.
Magnetization transfer changes in the normal appering white matter precede the appearance of enhancing lesions in patients with multiple sclerosis
Authors: Filippi Massimo , Rocca Maria A. , Martino Gianvito , Horsfield Mark A. , Comi Giancarlo
Published: January 2005

Serial monthly magenetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing‐remitting MS were scanned with a T1‐weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium‐DTPA (Gd‐DTPA). During each of the monthy sessions, MT and dual dual echo scans were also performed before Gd‐DTPA injection. On coregistered images, the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their apperance. Forty‐eight new enhancing lesions with no corressponding abnormalities, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions becomes evident on conventional MRI scans.
Surgical outcome in occipital lobe epilepsy: Implications for pathophysiology
Authors: Aykut‐Bingol Canan , Bronen Richard A. , Kim Jung H. , Spencer Dennis D. , Spencer Susan S.
Published: January 2005

Medically refractory occipital lobe epilepsies are increasingly treated with surgery, but outcome and its relationship to etiology, pathological substrate, occipital lobe location, surgical approach, and electroclinical features have not been systematically investigated in a substantial group of patients. Thirty‐five patients who underwent surgery for intractable occipital lobe seizures were retrospectively evaluated. Outcome and occipital lobe location were analyzed with respect to surgical procedure, pathology, clinical seizure characteristics, seizure onset and termination locations, and localization of interictal spikes. Most patients had developmental abnormalities (14) or tumors (13, all gliomas). Developmental abnormalities consisted of focal cortical dysplasia (5), heterotopia (2), hamartoma (3), cortical duplication (1), polymicrogyria (1), Sturge‐Weber syndrome (1), and tuberous sclerosis(1). There was 1 patient with a vascular abnormality, 1 with chronic inflammatory changes, 4 with gliosis, 1 with cerebral ossification, and 1 with normal pathology. Developmental abnormalities had significantly worse outcome (45% excellent/good) than tumors (85% excellent/good). In the developmental group, low‐grade focal cortical dysplasias had better outcome than heterotopia and hamartoma regardless of type of surgical procedure. Pathological groups did not significantly differ with respect to location within the occipital lobe (overall medial [50%] or lateral [38%]); clinical seizure characteristics referable to specific lobe (occipital [14%], temporal [34%], frontal [23%], more than one type [29%]); electroencephalographic localization (to occipital [17%], temporal [27%], or other/multifocal locations [56%]); or intracranial ictal onset or termination location. Electroclinical variables were also unrelated to the occipital lobe location of abnormality. Surgical outcome was not predicted by surgical approach (lesion excision with margins or lobectomy). The main pathological substrates of uncontrolled occipital lobe epilepsy are gliomas and developmental abnormalities. Whereas resection of occipital lobe tumors associated with chronic epilepsy produces nearly uniform seizure control, outcome after resection of occipital lobe developmental abnormalities is less uniform.
Multiple sclerosis: The increased frequency of the ICAM‐1 exon 6 gene point mutation genetic type K469
Authors: Mycko Marcin P. , Kwinkowski Marek , Tronczynska Ewa , Szymanska Bozena , Selmaj Krzysztof W.
Published: January 2005

Intracellular adhesion molecule‐1 (ICAM‐1) plays an important role in the cascade of adhesion events in the homing of inflammatory cells to the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Two single‐base ICAM‐1 polymorphisms have been described, in exons 4 and 6, changing codons 241 and 469 in the ICAM‐1 gene, respectively. Both polymorphisms result in amino acid changes and can potentially lead to different interactions of ICAM‐1 with its ligands. To detect ICAM‐1 gene polymorphisms in MS, we have developed a highly sensitive and site‐specific, two‐stage, nested polymerase chain reaction. Genomic DNA was extracted from blood cells of 79 MS patients and 68 control subjects. The results were confirmed by direct dideoxy chain termination sequencing. The frequency of exon 6 allele T was found to be significantly higher in MS patients than in controls (68% vs 49%). Most interesting, the frequency of exon 6 homozygote K469 was significantly higher in MS patients than in controls (53% vs 34%). Higher frequency of the K469 genotype was found to be independent of possible linkage with the previously described MS susceptibility factor, the HLA class II DR2 allele. In the present study, we have shown for the first time the ICAM‐1 gene polymorphisms in MS. The results indicate increased frequency of ICAM‐1 exon 6 allele T in MS patients, which may contribute to the MS genetics background.
Genetic characteristics of myoadenylate deaminase deficiency
Authors: Verzijl H. T. F. M. , van Engelen B. G. M. , Luyten J. A. F. M. , Steenbergen G. C. H. , van den Heuvel L. P. W. J. , ter Laak H. J. , Padberg G. W. , Wevers R. A.
Published: January 2005

Two types of myoadenylate deaminase (MAD) deficiency have been described, primary or inherited, and secondary or acquired MAD deficiency. In this study, we investigated whether secondary MAD deficiency is indeed acquired or merely coincidental. We demonstrated the same underlying molecular defect, a C34T transition, in both types of deficiency. Furthermore, the same frequency of the mutant MAD allele was found in the general population as in patients with neuromuscular complaints. We therefore conclude that in the Dutch population, secondary MAD deficiency is merely a “coincidental” finding, and that MAD deficiency is a harmless genetic variant.
Perinatal hypoxic—Ischemic thalamic injury: Clinical features and neuroimaging
Authors: Roland Elke H. , Poskitt Kenneth , Rodriguez Estela , Lupton Brian A. , Hill Alan
Published: January 2005

A common pattern of hypoxic–ischemic cerebral injury in the term newborn involves predominantly cerebral cortex and subcortical white matter. We describe 20 term newborns with moderate or severe acute hypoxic–ischemic encephalopathy who exhibit a different pattern of abnormalities on computed tomography, with evidence of decreased tissue attenuation predominantly in thalami and basal ganglia and relative preservation of cerebral cortex and white matter. Profound, acute hypoxic–ischemic insult (eg, umbilical cord prolapse, uterine rupture, or massive placental abruption) was documented in 16 of 20 infants (80%). Characteristic clinical features during the newborn period included irritability, tonic posturing of limbs, and persistent lower cranial nerve dysfunction, often with prominent tongue fasciculations. This pattern of central injury appears to be highly predictive of poor outcome; 7 newborns (35%) died, and all survivors who had follow–up to 18 months of age (11) had major neurological sequelae (eg, spastic quadriplegia, choreoathetosis, and persistent feeding problems). This pattern of hypoxic–ischemic cerebral injury corresponds closely to experimental animal models of “acute total” perinatal asphyxia.
Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor
Authors: Ohno Kinji , Anlar Banu , Özdirim Emire , Brengman Joan M. , DeBleecker Jan L. , Engel Andrew G.
Published: January 2005

We report and functionally characterize five new mutations of the acetylcholine receptor (AChR) in 11 Turkish patients with recessive congenital myasthenic syndromes (CMS)s belonging to six families. All mutations are in the ε‐subunit gene. Parental consanguinity is present in three families. The disease cosegregates with homozygous mutations in five families and with two different heteroallelic mutations in one family. Four mutations are frameshifting, predicting truncation of the ε subunit, and one occurs at a splice donor site. Expression of each frameshifting mutation and the likely transcripts of the splice‐site mutation in human embryonic kidney 293 cells shows that each mutation is a null mutation. The findings support the notion that loss‐of7hyphen;function mutations of the acetylcholine receptor causing CMS are concentrated in the ε subunit, and that such mutations are a frequent cause of CMS.
Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia
Authors: Fullerton Heather J. , Ditelberg Jeremy S. , Chen Sylvia F. , Sarco Dean P. , Chan Pak H. , Epstein Charles J. , Ferriero Donna M.
Published: January 2005

Unlike the mature animal, immature mice transgenic for copper/zinc superoxide dismutase (SOD1) have greater brain injury after hypoxia–ischemia than their wild‐type nontransgenic littermates. To assess the role of oxidative stress in the pathogenesis of this injury, we measured histopathological damage, lipid peroxidation products, enzymatic activities of catalase and glutathione peroxidase, and hydrogen peroxide (H2O2) concentration in these animals before and after hypoxic–ischemic injury. Lipid peroxidation products were significantly increased 2 hours after the insult in both transgenic and nontransgenic brains in hippocampus, the most damaged brain region. Catalase activity did not increase in response to SOD1 overexpression or injury in either group. However, glutathione peroxidase activity, unchanged in response to overexpression, decreased significantly 24 hours after injury in both groups. At 24 hours after injury, greater H2O2 accumlation was observed in transgenic brains. Because SOD1 dismutates superoxide to H2O2, overexpression of SOD1 in the presence of developmentally low activities of the catalytic enzymes glutathione peroxidase and catalase leads to an increased production of H2O2, and may explain the increased brain injury observed after hypoxia–ischemia in neonatal SOD1 mice.
Clinical and genetic evaluation of a family with a mixed dystonia phenotype from south tyrol
Authors: Klein Christine , Pramstaller Peter P. , Castellan Claudio C. , Breakefield Xandra O. , Kramer Patricia L. , Ozelius Laurie J.
Published: January 2005

The gene causing early‐onset torsion dystonia (DYT1) has recently been identified, and two new dystonia genes, one for adult‐onset focal dystonia (DYT7) and one for a mixed dystonia phenotype (DYT6), have been mapped. We evaluated clinically a family from South Tyrol (Northern Italy) with 6 definitely affected individuals who display an unusually large phenotypic range of dystonic symptoms. We excluded the GAG deletion in the DYT1 gene and linkage to any of the above‐mentioned dystonia loci, thus suggesting an as yet undefined dystonia gene in our family.
Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy
Authors: Yenari Midori A. , Fink Sheri L. , Sun Guo Hua , Chang Louis K. , Patel Maitrya K. , Kunis David M. , Onley David , Ho Dora Y. , Sapolsky Robert M. , Steinbrg Gary K.
Published: January 2005

Brain areas damaged by stroke and seizures express high levels of the 27‐kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp 72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin‐induced seizures.
Posterior vermal split syndrome
Authors: Bastian Amy J. , Mink Jonathan W. , Kaufman Bruce A. , Thach W. Thomas
Published: January 2005

We have studied a battery of movements in 5 children (age, 6–15 years) after transection of the posterior inferior cerebellar vermis. In each case, the surgery destroyed the midline vermis only (ranging from lobules VI–X). Tandem gait was badly impaired in all subjects. No subjects had impairments of kicking, reaching, pinching, or speech. Regular gait, standing, and hopping on one leg were relatively unimpaired. Cutting the parallel fibers that cross the midline may be the critical variable causing incoordination in tandem gait.
Amelioration of flulike symptoms at the onset of interferon β‐ 1b therapy in multiple sclerosis by low‐dose oral steroids is related to a decrease in interleukin‐6 induction
Authors: MartíNez‐CáCeres E. M. , Río J. , Barrau M. , Durán I. , Borrás C. , Tintoré M. , Montalban X.
Published: January 2005

Low‐dose oral steroid use at the onset of interferon β‐1b (IFNβ‐1b) therapy in relapsing‐remitting multiple sclerosis (RR‐MS) patients reduces flulike symptoms. To determine the mechanism by which steroid treatment minimizes these side effects, we analyzed the percentage of interleukin‐6 (IL‐6)–, interferon‐γ (IFN‐γ)‐, tumor necrosis factor α (TNF‐α)–, and IL‐10–producing cells before and after 3 months of IFNβ‐1b therapy onset. Our results support a relationship between IL‐6 induction and fever. Such side effects can be ameliorated by steroids.
Malignant glioma: Who benefits from adjuvant chemotherapy?
Authors: Deangelis Lisa M. , Burger Peter C. , Green Sylvan B. , Cairncross J. Gregory
Published: January 2005

We combined two randomized prospective Brain Tumor Study Group data sets to analyze the effects of prognostic factors on survival by treatment group. Adjuvant chemotherapy increased long‐term survival regardless of prognostic factors. Pathological review revealed that oligodendrogliomas were overrepresented among long‐term survivors independent of therapy. Prognostic factors do not predict benefit from adjuvant nitrosourea in malignant gliomas, and long‐term survival with chemotherapy is not explained by oligodendroglial tumors.
Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus
Authors: Brundin L. , Svenungsson E. , Morcos E. , Andersson M. , Olsson T. , Lundberg I. , Wiklund N. P.
Published: January 2005

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.
Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2
Authors: Scheffer Ingrid E. , Phillips Hilary A. , O'Brien Catherine E. , Saling Michael M. , Wrennall Jacqueline A. , Wallace Robyn H. , Mulley John C. , Berkovic Samuel F.
Published: January 2005

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75–43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome‐wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.
Vigabatrin increases human brain homocarnosine and improves seizure control
Authors: Petroff Ognen A. C. , Mattson Richard H. , Behar Kevin L. , Hyder Fahmeed , Rothman Douglas L.
Published: January 2005

Homocarnosine, a dipeptide of γ‐aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4–1.0 μmol/g) than in other animals. The antiepileptic drug vigabatrin increases human cerebrospinal fluid homocarnosine linearly with daily dose. By using 1H nuclear magnetic resonance spectroscopy, serial occipital lobe GABA and homocarnosine concentrations were measured in 11 patients started on vigabatrin. Daily low‐dose (2 g) vigabatrin increased both homocarnosine and GABA. Larger doses of vigabatrin (4 g) further increased homocarnosine but changed GABA levels minimally. Seizure control improved with increasing homocarnosine and GABA concentrations. Patients whose seizure control improved with the addition of vigabatrin had higher mean homocarnosine, but the same mean GABA concentrations, than those whose seizure control did not improve. Increased homocarnosine may contribute to improved seizure control.
Bilateral high‐frequency stimulation of the internal globus pallidus in advanced Parkinson's disease
Authors: Volkmann J. , Sturm V. , Weiss P. , Kappler J. , Voges J. , Koulousakis A. , Lehrke R. , Hefter H. , Freund H.‐J.
Published: January 2005

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off‐period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3‐month follow‐up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication‐off state was reduced from 54.1 ± 14.8 to 23.9 ± 11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow‐up at 6 months (n = 6), 9 months (n = 6), and 12 months (n = 4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high‐frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for “off” symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.
A dystrophin missense mutation showing persistence of dystrophin and dystrophin‐associated proteins yet a severe phenotype
Authors: Goldberg Laura R. , Hausmanowa‐Petrusewicz Irena , Fidzianska Anna , Duggan David J. , Steinberg Lisa S. , Hoffman Eric P.
Published: January 2005

A muscle biopsy from an X‐linked muscular dystrophy pedigree showed normal dystrophin and dystrophinassociated proteins. Linkage to multiple markers within the dystrophin gene (LOD = 2.7, ⊖ = O) indicated a primary dystrophinopathy. Sequencing of the entire dystrophin RNA revealed a single missense mutation (D3335H) in the unique carboxyl‐terminal domain. This is the first report showing that a relatively severe dystrophinopathy can occur despite the correct localization of dystrophin and dystrophin‐associated proteins.
The development of the pillar cells, tunnel space, and Nuel's spaces in the organ of Corti
Authors: van der Stricht O.
Published: January 2005

The tunnel space is developed around the spiral nerve bundle, which runs between the nucleated portions of the inner and outer pillar cells. It is originally an intercellular cleft, the fluid contents of which are elaborated in the vacuolated cyto plasm of the pillar cells and discharged into the adjoining space. Parts of this secreting protoplasm undergo a process of cytolysis or liquefaction, so that the cleft enlarges and the fluid contents increase in quantity at their expense.
Studies of living nerves. III. Phenomena of nerve irritation and recovery, degeneration and repair
Authors: Speidel Carl Caskey
Published: January 2005

The reaction of single internodal segments of myelinated nerve fibers of living frog tadoples have been observed in minute detail, following many varieties of experimental irritation of both acute and chronic types. The changes that characterize nerve irritation bear a marked resemblance to the early changes that characterize tgrophic (wallerian) de generation after nerve section.
The membranous parts of the brain, meninges and their blood vessels in Amblystoma
Authors: Herrick C. Judson
Published: January 2005

The meninges, endolymphatic organs, and membranous parts of the brain of adult A. Tigrinum have been examined microscopically and the realted blood vessels are described in detail.
The olfactory centers and connections in the cerebral hemisphere of the mole (scalopus aquaticus machrinus)
Authors: Johnson Thomas N.
Published: January 2005

No Asbtract.
Localization of the terminals of the tongue afferents in the nucleus of the solitary tract
Authors: Blomquist A. J. , Antem A.
Published: January 2005

The nerves innervating the tongue were stimulated electrically and multineuron responses were recorded in the nucleus of the solitary tract. Stimulation of the chorda tympani and the IXth nerves evoked responses in the lateral and medial ipsilateral solitary nucleus in a rostral‐caudal order. Responses to lingual nerve stimulation were found only in the lateral, larger‐celled portion of the ipsilateral solitary nucleus overlapping the chorda tympani and the IXth nerve areas. Stimulation of the above three nerves also evoked somewhat longer latency responses in the ambiguus nucleus. Responses to lingual nerve stimulation were found in the XIIth nerve motor nucleus and the solitary nucleus at the level of the obex using high voltage levels of stimulation. The results were discussed in terms of the anatomical discreteness of the relays of the gustatory and the other tongue modalities in the solitary nucleus. These results were obtained in the white rats.
Post‐natal growth of neuroglia cells and blood vessels of the cervical spinal cord of the albino mouse
Authors: Sakla Francois B.
Published: January 2005

The post‐natal growth of three types of neuroglia cells viz. Astroglia, oligodendroglia and microglia cells and the growth of the blood vessels of the cervical spinal cord of the albino mouse were studied at the following ages: 1, 10; 20, 30 and 120 days in preparations stained with: Golgi‐Cox, Rio‐Hortega and Gallocyanin stains.

Their total number was doubled in the first ten days as a result of mitoses in the ependymal cells of the central canal forming new astroglia and oligodendroglia cells in both the gray and white matter and mitoses in the cells of the pia‐mater which form new microglia cells. After the tenth day their total number became fixed and thus they were dispersed in the cord until the 120th day. A correlation was established between the increase in the number of oligodendroglia cells and myelination.

The total number of cells forming the wall of the central canal was estimated.

In mice successfully injected with China ink the blood vessels in the gray and white matter respectively were measured. Their total length and total volume were estimated. A correlation between the vascularization of the cord and the process of myelination, growth of the nerve cells and neuroglia cells was established.
The forebrain of the guinea pig in stereotaxic coordinates
Authors: Tindal J. S.
Published: January 2005

A stereotaxic atlas has been prepared of the forebrain of the guinea pig (body weight 700–830 g) using a standard cat‐monkey stereotaxic instrument. The coordinates used were the vertical interaural plane (APO) and the horizontal orbital‐interaural plane (HO). The atlas consists of transverse sections of the brain taken at 0.5 mm intervals from A5 through A15.
Geniculo‐striate connections in the rabbit. II. Cytoarchitectonic structure of the striate region and of the dorsal lateral geniculate body; organization of the geniculo‐striate projections
Authors: Rose Jerzy E. , Malis Leonard I.
Published: January 2005

Retrograde changes in the dorsal lateral geniculate body were studied following cortical radiation lesios.

The cytoarchitectonic structure of the striate region is described. The peristriate as well as the striate areas are shown to receive projections form the dorsal lateral geniculate body. Thus — as far as this set of connections is concerned — the peristriate are is a subdivision of the striate region. It is further shown that the striate region as defined cytoarchitectonically is —to the extent that it was validated — coextensive with the cortical projection area of the dorsal lateral geniculate body.

The dorsal lateral geniculate body is divided into an alpha and a beta sector. Evidence indicates that each vertical column of cells in the striate region receives projections from an appropriate geniculate column which extends throughout the thickness of the alpha sector. The alpha cell columns project upon the striate region in an orderly manner. Details of this organization are described.

The cells of the beta sector also project upon the striate region. Whether the pattern of this projection is similar to that of the alpha sector or is more generalized has not been established.

Some electrophysiological and experimental‐anatomical evidence relevant to the findings is discussed.
Cellular localization of monoamines in the upper brain stem of the pigeon
Authors: Fuxe Kjell , Ljunggren Lars
Published: January 2005

With the help of a highly sensitive and specific fluorescence method developed by Falck and Hillarp, in combination with a pharmacological approach, it has been possible to demonstrate the presence in birds of specific Neurons of two distinctly different types, which in all probability form and store a primary catcholamine and 5‐hydroxytryptamine respectively. The amines are in low concentrations in the cell bodies and axons but stored in very high concentrations in the terminals, especially in the abundant varicosities. At least three large ascending monoamine systems appear to be present within the upper brain stem. Many — if not most — of the ascending fibers arise in all probability from cell bodies within the mesencephalon and run rostrally mainly in the medial forebrain bundle. Two of the Neuron systems produce and store a primary catecholamine, one probably giving rise mainly to terminals within the hypothalamus and the preoptic area, the other within the corpus striatum. The remaining system produces and stores 5‐hydroxytryptamine.

The modified ependyma seems to consist — at least partly — of two types of cells forming and storing either a primary catecholamine or 5‐hydroxytryptamine.
The pyramidal tract of tupaia, compared to that in other primates
Authors: Verhaart W. J. C.
Published: January 2005

The pyramidal tract of Prosimii proves to lack coarse fibers and to be much smaller than in Macaca, whereas in Saimiri it resembles the latter very much. Crossing and course within the cord in the Prosimii examined are identical to those in Macaca and Man. In Tupaia the pyramidal tract is very different, as it is very small, crosses to the dorsal funiculus and ends in the lower theoracic levels.

The other large tracts descending into the cord seem to enlarge where the pyramidal tract decreases in size and length in Tupaia. The large difference between the pyramidal tract of Tupaia and that of other Prosimii is emphasized.
Contribution to the quantitative study of the nervous tissue. A new method for measurement of the volume and surface area of neurons
Authors: Mannen Hajime
Published: January 2005

In our histological analysis of the brain stem of the kitten with the Golgi‐Cox method, it was found that the application of reflecting illumination provides a clear outline of the soma surface including its relationship with the dendrites. Utilizing this method of illumination it was possible to develop a new approach for following the total course of dendrites in successive serial sections and a method for the photogrammetrical representation of neuron soma by means of microscopic stereophotograms. This has provided a means for estimating precisely the dimensions of the neuron.

Five cells of the magnocellular nucleus of bulbar and pontine reticular formation have been measured as test cases by means of this new method. The following results were obtained: the mean area and volume of the neuron soma obtained by means of photogrammetry are 13,580μ2 and 109,820μ3 respectively; the area and volume of the entire dendritic portion of the neuron are 66,640 μ2 and 70,060 μ3 respectively. In the case of serial sections 250 μ thick, about 25% of the dendrites are lost in the neighboring sections with respect to length, and 16% to 14% with respect to area and volume. Thus the ratios of the dendritic area to the soma area and that of the dendritic volume to the soma volume average 5.1 and 0.6 respectively.
Lumbosacral dorsal root terminations in the nucleus gracilis of the cat. Some observations on terminal degeneration in other medullary sensory nuclei
Authors: Hand Peter J.
Published: January 2005

Following lumbosacral dorsal rhizotomies (L1, L5, L6 and S1), fiber degeneration could be traced throughout three rostro‐caudal regions of nucleus gracilis by utilizing the Nauta method. In rostral region, fiber degeneration was less dense and localized with greater intersegmental overlap than in middle region, where roots terminated in fairly specific cell clusters. Little could be stated about the caudal region because of sparsity of terminal degeneration. Fiber degeneration in rostral region appeared to be distributed primarily in the dendritic fields while that in the middle region terminated on both cell somata and dendrites. Overlap of dermatomes in periphery and centrally in nucleus parallel each other. Throughout the nucleus, greatest overlap of root distribution was encountered in more ventral regions. A root supplying a more distal dermatome (e.g. L6) compared to a more proximal one (e.g. L1), terminates more densely and dorsally in the nucleus. An occasional degenerated fiber passed into the contralateral gracile nucleus at obex level. Root degeneration proceeded, ipsilaterally, into rostro‐dorsal regions of lateral cuneate, cuneate, and caudo‐lateral regions of 2 nuclei. Bilateral degeneration from all roots, excepting S1, was noted in rostral pole of subnucleus caudalis and the subnucleus interpolaris of spinal trigeminal complex and nucleus reticularis parvicellularis. The pathway to the spinal trigeminal and parvicellular nuclei was undetermined. The concept of the non‐homogenous organization of the gracile nucleus was supported.
The organization of the posterior ventral cochlear nucleus in the rat
Authors: Harrison J. M. , Irving R.
Published: January 2005

The ventral cochlear nucleus was examined in 31 rats' brains prepared according to the protargol method of Bodian. The following regions were delimited on the basis of synaptic, cellular and axonal criteria.

Region II, which occupies the central part of the nucleus, consists principally of cells (type g)which receive modified bulbs of Held from the acoustic nerve and which send large axons to the trapezoid body. The cells were graded in size, the smallest (high frequency) being located dorsally and the larges (low frequency) being located ventrally. Associated with region II are the cells (type b) of the acoustic nerve nucleus. These cells receive boutons from the acoustic nerve and send very large axons to the trapezoid body.

Region IV is located in the posterior part of the ventral cochlear nucleus and is composed of large multipolar cells (type k). The dendrites of these cells are specifically organized with respect to the fibers of the acoustic nerve. Synaptic endings, from the descending branch of the acoustic nerve, consist of boutons on cell body and dendrites. The axons of these cells compose the stria of Held.

Region V is located in the posterior part of the ventral cochlear nucleus and appeared to have only intrinsic connections.

All regions received synaptic endings in addition to those which arose from the acoustic nerve.
The projection of optic fibers to the visual centers in the cat
Authors: Laties Alan M. , Sprague James M.
Published: January 2005

Retinal projections to the thalamus and midbrain were studied by the Nauta‐Laidlaw technique. After unilateral enucleation, degeneration was found in five areas: dorsal lateral geniculate nucleus (LGNd, thalamus), ventral lateral geniculate nucleus (LGNv, subthalamus), nucleus of optic tract (NOT, pretectum), superior colliculus (S.C., tectum), and accessory optic nuclei (AON, tegmentum). Degeneration after focal lesions in nasal retina made by photocoagulation is found in four areas of the contralateral LGNd: Laminae A and B, nucleus interlaminaris centralis (NIC), and the medial part of nucleus interlaminaris medialis (NIM). Temporal lesions lead to degeneration ipsilaterally in three areas: lamina A1, NIC, and the lateral part of NIM. Central lesions are followed by bilateral projections; the area of degeneration on each side is greater than that of peripheral lesions of comparable size. Focal degeneration is found in NIM after either central or peripheral retinal lesions. Each retina projects to both NOT and both S.C. In NOT, degeneration following nasal lesions is strictly contralateral while after temporal lesions is mainly ipsilateral. A bilateral projection of temporal retina to NOT constitutes an exception to theories of chiasmal decussation. Both nasal and temporal projections to AON are wholly crossed, thus constituting another example of projection of temporal retina to the contralateral side, Nasal fibers project contralaterally and nearly all temporal fibers ipsilaterally to S.C.
Sprouting of optic tract projections in the brain stem of the rat
Authors: Goodman Donald C. , Horel James A.
Published: January 2005

The present experiments examine axonal sprouting of optic tract projections as a consequence of occipital cortex removal. Eyes were removed bilaterally in experimental rats 16 months following unilateral occipital cortex ablation. Seven animals survived this procedure. Controls included rats sacrificed 16 months after unilateral occipital cortex ablation, one week after unilateral occipital cortex destruction, and one week after bilateral or unilateral eye removal. Brains were serial‐sectioned and stained by the Nauta‐Gygax method for degenerating axons.

Sprouting occurred only at two loci, the caudal half of the ventral lateral geniculate nucleus, pars lateralis, and the caudal portion of lateral nucleus of the optic tract and subjacent medial quarter of pretectal nucleus. These loci have in common that they are regions of convergence in a major fashion of the two fiber systems, the occipitofugal and retinofugal projections on which experiments were done. However, sprouting did not occur in other similarly deafferented regions. Explanations for this specificity of sprouting are discussed.

Optic tract sprouting was observed only at paraterminal portions of the axon and not as collateral sprouts along its course.

A suggested relationship between axonal sprouting and functional plasticity is discussed.
Fiber degeneration after lateral hypothalamic lesions in the rat
Authors: Wolf George , Sutin Jerome
Published: January 2005

Fiber degeneration in the rat following lesions of the lateral hypothalamic area was studied by the method of Nauta and Gygax ('54). Ascending degeneration in the medial forebrain bundle enters the preoptic area and the medial and fimbrial nuclei of the septum. Less dense degeneration is found in the lateral septal nucleus and a few fibers bypass the septum and reach the cingulate cortex. Descending degeneration in the medial forebrain bundle enters the ventral tegmental area of Tsai giving off a few fibers to the mammillary bodies on the way. In the midbrain fibers turn dorsomedially to enter the raphe nuclei and the central gray and dorsolaterally to enter the nucleus mesencephalicus profundus pars lateralis. A small group of fibers leaves the anterior part of the lateral hypothalamus in a dorsomedial direction and passes through the inferior thalamic peduncle and stria medullaris to enter the lateral habenular nucleus. Another bundle leaves the posterior part of lateral hypothalamus in a dorsomedial direction and passes through the posterior midline thalamus to enter the central gray. No degeneration was found in the ventromedial hypothalamus in rats with lateral hypothalamic lesions. Our ability to stain fine degenerating fibers in this region was demonstrated in rats with medial hypothalamic lesions.
The postnatal development of neocortical neurons in the dog
Authors: Fox Michael W. , Inman Ottilie R. , Himwich Williamina A.
Published: January 2005

Examinations were made by means of the Golgi‐Cox method of the developing neuronal elements of the cortex of the dog during the first ten weeks of life. The neuronal elements undergo gradual morphological differentiation during the first week. From 2–4 weeks of age the most dramatic changes in the development of dendritic arborizations occur. After this time the changes are slower with terminal maturation of cellular elements, cessation of neuronal growth and final organization of apical and basilar dendrites and their collaterals. Comparison with the development of the kitten shows close similarity in the development of canine and feline neocortex. In dogs, however, an essentially mature neocortex is not reached until after four weeks of age. The relation of these data to biochemical and electrophysiological development and behavioral patterns in the young dog is discussed.