bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia
Authors: Schwarcz Robert , Tamminga Carol A. , Kurlan Roger , Shoulson Ira
Published: January 2005

The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug‐free patients suffering from Huntington's disease or schizophrenia (control group). In both diseases, quinolinic acid concentrations were highly variable (< 4–48 nM) but the mean levels for each disease group were not significantly different from each other or from the quinolinic acid concentration of normal cerebrospinal fluid. Analysis of steady‐state cerebrospinal fluid quinolinic acid concentration is unlikely to be of value as a diagnostic tool in Huntington's disease.
Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease
Authors: Kaye Jeffrey A. , May Conrad , Atack John R. , Daly Eileen , Sweeney Daniel L. , Flint Beal M. , Kaufman Seymour , Milstien Sheldon , Friedland Robert P. , Rapoport Stanley I.
Published: January 2005

Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin‐like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age‐matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly Decemberreased. 5‐Hydroxyindole‐acetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results, suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.
Neurological abnormalities associated with remote occupational elemental mercury exposure
Authors: Albers James W. , Kallenbach Lee R. , Fine Lawrence J. , Langolf Gary D. , Wolfe Robert A. , Donofrio Peter D. , Alessi Anthony G. , Stolp‐Smith Kathryn A. , Bromberg Marchk B. ,   Mercury Workers Study Group
Published: January 2005

We examined 502 subjects, 247 of whom had occupational elemental mercury exposures 20 to 35 years previously, to identify potential exposure‐related neurological abnormalities. Few significant (p < 0.05) differences existed between exposed and unexposed subjects. However, multiple linear regression analysis demonstrated several significant correlations between Decemberlining neurological function and increasing exposure as determined by urine mercury measurements from the exposure interval. Subjects with urine mercury peak levels above 0.6 mg/L demonstrated significantly Decemberreased strength, Decemberreased coordination, increased tremor, Decemberreased sensation, and increased prevalence of Babin‐ski and snout reflexes when compared with the remaining subjects. Furthermore, subjects with clinical polyneuropathy had significantly higher peak levels than normal subjects (0.85 vs 0.61 mg/L; p = 0.04), but not increased exposure duration (20.1 vs 20.8 quarters; p = 0.34), and 28% of subjects with peak levels above 0.85 mg/L had clinical evidence of polyneuropathy, compared with 10% of remaining subjects (p = 0.005). Although exposure was not age dependent, several neurological measures showed significant age‐mercury interaction, suggesting that natural neuronal attrition may unmask prior exposure‐related subclinical abnormalities.
HTLV‐I‐associated myelopathy: Oligoclonal immunoglobulin G bands contain anti‐HTLV‐I p24 antibody
Authors: Grimaldi Luigi M. E. , Roos Raymond P. , Devare Sushilkumar G. , Casey James M. , Marchuo Yasunori , Hamada Takeshi , Tashiro Kunio
Published: January 2005

Human T‐cell lymphotropic virus type I (HTLV‐I)‐associated myelopathy (HAM) and tropical spastic paraparesis belong to a new group of neurological diseases associated with retroviral infection. An HTLV‐I‐like virus has recently been implicated in multiple sclerosis as well. We studied paired cerebrospinal fluid and serum specimens from HAM and multiple sclerosis patients by isoelectric focusing and an isoelectric focusing HTLV‐I p24 overlay technique to clarify the role of HTLV‐I in these diseases. We detected oligoclonal bands by isoelectric focusing with silver‐staining in cerebrospinal fluid, but not serum, from all 5 HAM and all 9 multiple sclerosis patients. An isoelectric focusing HTLV‐I p24 overlay technique demonstrated anti‐p24 antibody in HAM cerebrospinal fluid at a different pI distribution than that seen in paired serum, indicating local synthesis of anti‐p24 antibody within the central nervous system. Oligoclonal bands in HAM cerebrospinal fluid corresponded in pI distribution to anti‐p24 antibody activity, suggesting the presence of an ongoing HTLV‐I infection in the central nervous system. Multiple sclerosis patients had no evidence of anti‐HTLV‐I activity by p24 radioimmunoprecipitation assay, Western immunoblots, or isoelectric focusing HTLV‐I p24 overlay analysis. Our data support a role for HTLV‐I as an etiological agent in HAM, but not in multiple sclerosis.
McArdle's disease: Biochemical and molecular genetic studies
Authors: Servidei Serenella , Shanske Sara , Zeviani Massimo , Lebo Roger , Fletterick Robert , DiMauro Salvatore
Published: January 2005

We have analyzed muscle biopsy specimens from 48 patients with biochemically proven phosphorylase deficiency (McArdle's disease) by sodium doDecemberylsulphate polyacrylamide gel electrophoresis (SDS‐PAGE), immunoblotting, and immunotitration (enzyme‐linked immunosorbent assay [ELISA]). Thirty‐five of the 42 patients studied by SDS‐PAGE and immunoblot, and 41 of the 48 patients studied by ELISA had no detectable enzyme protein. Six patients had Marchkedly Decemberreased phosphorylase protein by all three assays, and only 1 patient had a normal amount of protein. No apparent correlation existed between the presence or absence of enzyme protein and the clinical presentation or muscle glycogen concentration. Northern analysis was performed on muscle RNA in 4 patients: messenger RNA was normal in 2, abnormally short in 1, and absent in the fourth, indicating heterogeneity 0of the molecular lesion in McArdle's disease.
Intraventricular hemorrhage in the premature infant—current concepts. Part I
Authors: Volpe Joseph J.
Published: January 2005

Although the incidence of periventricular‐intraventricular hemorrhage (IVH) has decreased in recent years, the increasing survival rates for the smallest premature infants indicate that the lesion will continue to be a major problem in neonatal intensive care facilities. The neuropathology is characterized by an elemental lesion, bleeding into the subependymal germinal matrix, with subsequent rupture into the lateral ventricle. Important neuropathological consequences are germinal matrix destruction, posthemorrhagic hydrocephalus, and periventricular hemorrhagic infarction. The last of these appears to be a venous infarction and is a critical determinant of neurological outcome. Neuropathological accompaniments, not caused by the IVH, include periventricular leukomalacia and pontine neuronal necrosis. The pathogenesis of IVHs is related to intravascular, vascular, and extravascular factors. Intravascular factors involve primarily control of blood flow and pressure in the microcirculation of the germinal matrix. Particular pathogenetic importance can be attached to fluctuations in cerebral blood flow, abrupt increases in flow, decreases in flow with injury to matrix vessels, increases in cerebral venous pressure, and, in selected infants, disturbances of platelet function and coagulation. Vascular factors relate to the microcirculation of the matrix, the site of the initial bleeding. A maturation‐dependent alteration in vascular integrity and a vulnerability of matrix vessels to ischemic injury appear important. Extravascular factors include those relevant to mesenchymal and glial support for matrix vessels and to local fibrinolytic activity in the germinal matrix. The latter may be a manifestation of the proteolytic activity now recognized to be of general importance in developmental remodeling of the mammalian central nervous system.
Benign versus chronic progressive multiple sclerosis: Magnetic resonance imaging features
Authors: Koopmans R. A. , Li D. K. B. , Grochowski E. , Cutler P. J. , Paty D. W.
Published: January 2005

The extent of disease as detected by magnetic resonance imaging was compared between 32 patients with benign multiple sclerosis (MS) and 32 patients with the chronic progressive form matched for age, sex, and disease duration. Computer‐assisted quantitation of magnetic resonance images revealed a higher mean lesion load in chronic progressive multiple sclerosis (CPMS); however, in approximately 20% of benign MS patients the lesion load was higher than that in the CPMS patients. CPMS patients had a higher number of infratentorial lesions, yet similar numbers of supratentorial lesions, when compared with benign MS patients. The degree of confluency of lesions and the clinical expression of infratentorial lesions were typically higher in the CPMS patients. Benign MS was characterized by a lower degree of confluency and a higher number of asymptomatic infratentorial lesions. Thus, magnetic resonance imaging shows characteristic differences in magnetic resonance‐detected changes between MS patients with different clinical courses.
Dominantly inherited dementia and parkinsonism, with non‐alzheimer amyloid plaques: A new neurogenetic disorder
Authors: Rosenberg Roger N. , Green Joseph B. , White Charles L. , Sparkman Dennis R. , Dearmond Stephen J. , Kepes John J.
Published: January 2005

A family is described in which a dominant form of inheritance, probably autosomal dominant, expresses severe dementia and parkinsonism as the major clinical features. Neuropathological correlates in two autopsied members of this family consisted of extracellular hyaline eosinophilic, congophilic amyloid plaques in decreasing order of frequency in the cerebral cortex, basal ganglia, thalamus, and substantia nigra, and atrophy and gliosis of the basal ganglia and substantia nigra. The extracellular plaques did not stain with antibody raised against the prion protein nor with two separate anti‐amyloid A4 antibodies. The combination of dominantly inherited dementia with parkinsonism and extracellular plaques in this distribution that are amyloid and prion protein antibody negative has not been previously reported and thus may represent a new neurological genetic disorder.
The olfactory and cognitive deficits of parkinson's disease: Evidence for independence
Authors: Doty Richard L. , Riklan Manuel , Deems Daniel A. , Reynolds Constance , Stellar Stanley
Published: January 2005

In the present study we sought to determine whether the olfactory deficits of parkinsonism are related to the cognitive and perceptual‐motor manifestations of the disease. Pearson correlation coefficients were computed among a number of olfactory, neurological, and neuropsychological measures obtained from 58 Parkinson's disease patients, including the University of Pennsylvania Smell Identification Test, a modified Randt memory test, a reaction time test, a finger‐tapping test, ratings of motor and neurological function, and selected verbal and performance subtests of the Wechsler Adult Intelligence Scale–Revised. Data from 38 patients with Parkinson's disease who received odor detection threshold testing were also evaluated. The intercorrelation matrix was subjected to a principal components factor analysis which yielded six clear‐cut factors: cognitive/memory, gross motor, oral motor, fine motor, olfactory, and tremor. The olfactory factor received strong and nearly exclusive loadings from the olfactory measures (which did not evidence meaningful loadings on any of the other factors). A ten‐trial jackknife procedure revealed the factor structure to be stable. Further support of the independence of the olfactory variables from the other measures was provided by multiple regression and canonical correlation analyses. Overall, these findings lend support to the hypothesis that the olfactory disorder of parkinsonism is independent of the cognitive, perceptual‐motor, and memory manifestations of the disease.
Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis
Authors: Trotter John L. , Clifford David B. , McLnnis Jane E. , Griffeth Rogers C. , Bruns Kathy A. , Perlmutter Monica S. , Anderson Charles B. , Collins Kelly G. , Banks Geneva , Hicks Byron C.
Published: January 2005

Thirty untreated patients with clinically definite chronic progressive multiple sclerosis were matched with 10 patients with clinically stable definite multiple sclerosis and 16 patients with other neurological diseases. A group of 12 normal control (NC) volunteers was matched to these groups. All patients with chronic progressive multiple sclerosis and normal control subjects were analyzed for the concanavalin A suppressor assay, mitogen stimulation, and phenotyping of peripheral blood mononuclear cells. In addition, serum was analyzed for interleukin‐2 levels. Results of mitogen stimulation studies did not distinguish the groups. Concanavalin A–induced suppression was significantly decreased in the patients with chronic progressive multiple sclerosis (p < 0.01). Phenotyping of fresh cells showed an elevated CD4 : CD8 ratio in the patients with chronic progressive multiple sclerosis. Neither phenotyping nor concanavalin A–induced suppression correlated with or predicted the degree of disability, but the serum levels of interleukin‐2 correlated inversely with disability (p < 0.01) and directly with a poor prognosis after 18 months of observation (p < 0.05). Serum levels of interleukin‐2 decreased as the disease progressed.
Subarachnoid blood and headache: Altered trigeminal tachykinin gene expression
Authors: Linnik Matthew D. , Sakas Damianos E. , Uhl George R. , Moskowitz Michael A.
Published: January 2005

Sensory axons from the trigeminal ganglion (V) innervate cephalic blood vessels and use the preprotachykinin gene products, substance P (SP) and neurokinin A (NKA), as putative neurotransmitters conveying nociceptive information. Blood in the subarachnoid space is accompanied by severe headache. We now report that this painful stimulus, which should enhance activity in V, specifically alters tachykinin peptide and mRNA levels in V and perivascular axons. Marked reductions in SP levels were observed in basilar artery segments within 4 hours after intracisternal blood injection which persisted for 48 hours and recovered by 7 days. SP peptide levels in V were elevated by 49% two days after blood injection. The changes in SP peptide levels were accompanied by increases in ganglionic content of the preprotachykinin mRNA that codes for the peptide. Blood‐induced peptide depletion in arteries and subsequent increases in peptide and mRNA in V are consistent with increased neuronal activity and enhanced neuropeptide release. These results implicate the tachykinin‐utilizing trigeminovascular neurons in the sequelae of subarachnoid hemorrhage.
Ideational apraxia: A deficit in tool selection and use
Authors: Ochipa C. , Rothi L. J. G. , Heilman K. M.
Published: January 2005

We report a 67‐year‐old left‐handed man who exhibited an ideational apraxia in both clinical and nonclinical natural settings following a right hemisphere infarction. His inability to use tools could not be explained by a motor production deficit (ideomotor apraxia), because he made content errors and could not match tools with objects. His deficit could not be attributed to an agnosia or language comprehension deficit, because he could name tools and point to tools on command. Based on our testing, it appeared that this patient had a loss of knowledge related to tool use.
Nonconvulsive status epilepticus following cerebral angiography
Authors: Vickrey Barbara G. , Bahls Fredrick H.
Published: January 2005

A 64‐year‐old man developed lethargy and aphasia immediately following cerebral arteriography with iothalamate meglumine. An electroencephalogram showed continuous epileptiform activity. The patient was treated with intravenous phenytoin with complete resolution of clinical symptoms and electroencephalographic epileptiform abnormalities. The diagnosis of nonconvulsive status epilepticus should be considered in cases of altered consciousness following cerebral arteriography.
Neurological disease associated with antiphospholipid antibodies
Authors: Briley Dennis P. , Coull Bruce M. , Goodnight Scott H.
Published: January 2005

The Hemostasis and Thrombosis Laboratory at the Oregon Health Sciences University identified 80 patients with significantly elevated anticardiolipin antibody (ACLA) levels. We reviewed all of their available medical records and found that 25 of these patients had associated neurological symptoms or disorders. These symptoms and disorders could be grouped into four distinct clinical patterns comprising encephalopathy, multiple cerebral infarctions, migraine‐like headaches, and visual abnormalities including amaurosis fugax and ischemic optic neuropathy. Cerebral ischemia best explained these neurological dysfunctions. There was no correlation between the presence or absence of neurological disease and ACLA levels, but ACLA levels were higher in patients with encephalopathy than in others with neurological involvement (p < 0.05). How neurological dysfunction and the presence of these antiphospholipid antibodies are related remains to be clarified. Nevertheless, in patients with unexplained cerebral ischemia, establishing the presence of ACLA may have prognostic and therapeutic importance. In particular, acute immunosuppressive therapy and plasmapheresis may be useful in patients with acute ischemic encephalopathy.
Amaurosis fugax associated with antiphospholipid antibodies
Authors: Digre Kathleen B. , Durcan F. Jane , Branch D. Ware , Jacobson Dan M. , Varner Michael W. , Baringer J. Richard
Published: January 2005

In more than 50% of amaurosis fugax patients under 45 years of age no cause for the episodes of visual loss is identifiable. We have encountered 6 young adults (4 women and 2 men) with episodes of amaurosis fugax associated with elevated levels of antiphospholipid antibodies. Splinter hemorrhages of the nail beds were present in most patients. Treatment with antiplatelet medications and anticoagulants appeared to reduce the frequency of episodes and might prevent central retinal artery occlusions or stroke.
Diabetic truncal neuropathy: Topography of the sensory deficit
Authors: Stewart John D.
Published: January 2005

The distributions of sensory abnormalities in 17 episodes of diabetic truncal neuropathy among 7 patients with diabetes mellitus are described. The patterns are highly variable: the distribution of adjacent main spinal nerves may be involved, resulting in a complete dermatomal band of dysesthesia, but almost two‐thirds of the episodes were restricted to the distribution of the ventral or dorsal rami of the spinal nerves or branches of these rami or varying combinations of these distributions.
The time course of steroid action on blood‐to‐brain and blood‐to‐tumor transport of 82Rb: A positron emission tomographic study
Authors: Jarden J. O. , Dhawan V. , Moeller J. R. , Strother S. C. , Rottenberg D. A.
Published: January 2005

Blood‐to‐brain and blood‐to‐tumor transport rate constants for Rb (K1) and apparent tissue blood volume (Vb) were estimated in 8 patients with primary or metastatic brain tumors before and approximately 6 hours after a 100‐mg intravenous bolus injection of dexamethasone using 82Rb and positron emission tomography. Eight additional patients were studied to evaluate test‐retest variability and repositioning errors. Six hours following dexamethasone administration tumor K1 (but not Vb) was significantly reduced compared with contralateral control brain regions (p < 0.03). These data are consistent with our previously published 24‐hour‐postdexamethasone data and suggest that comparable effects of corticosteroids on brain/tumor capillaries may be observed at 5 to 6 and 24 hours. The time course of dexamethasone‐induced alterations in brain/tumor capillary permeability supports the view that these alterations may be responsible for at least some of the antiedema effects of corticosteroids.
An immunohistochemical investigation of the human neostriatum in huntington's disease
Authors: Goto Satoshi , Hirano Asao , Rojas‐Corona Rogelio R.
Published: January 2005

The neostriatum of 7 autopsied patients with Huntington's disease (HD) was examined immunohistochemically using purified antibody against calcineurin, which may be present only in the medium‐size spinous neurons of the mammalian striatum. This study revealed a marked loss of calcineurin‐positive cells in the caudate nucleus and the putamen in all HD patients, compared with control subjects, and there was some variation among the HD patients. Four HD patients showed significantly lower density of calcineurin‐positive cells in the caudate nucleus than in the putamen. The remaining calcineurin‐positive cells in the caudate nucleus and the putamen had a mosaic‐like pattern, demonstrating a subregional difference in distribution. This finding suggests that there are subregional as well as compartmental differences in the vulnerability of the calcineurin‐positive cells in the striatum of patients with HD.
Juvenile myoclonic epilepsy: An autosomal recessive disease
Authors: Panayiotopoulos Chrysostomos P. , Obeid Tahir
Published: January 2005

We undertook genetic study of patients with juvenile myoclonic epilepsy (JME) from 17 families. There was a mean of 8 children in each sibship. Siblings were affected in 8 sibships, and some families had more than 2 members affected by JME. Half‐siblings and parental involvement were found in only 1 sibship each. The segregation ratio was 0.123 but increased to 0.18 with correction for age of onset. Parental consanguinity was found in 9 (45%) of the sibships. The evidence establishes an autosomal recessive mode of inheritance for JME.
Amyotrophic lateral sclerosis: Abnormalities of the tongue on magnetic resonance imaging
Authors: Cha Choon H. , Patten Bernard M.
Published: January 2005

We compared the magnetic resonance images of the tongues of 16 amyotrophic lateral sclerosis (ALS) patients with those of 20 control patients and found the tongue in ALS patients is more frequently and more severely involved than suspected clinically, with major abnormalities of size, shape, position, and internal structure. The tongue size in ALS, as measured in the sagittal plane, can be reduced by as much as two‐thirds of normal. The shape of the tongue in ALS tends to be rectangular or square rather than curved as is normal. As severity of the disease increases, the position of the tongue changes so that the bulk of the muscle falls away from the incisors and no longer is in contact with the hard or soft palate. The normal radial bands from the anterior floor of the mouth to the mucosal surface are often missing in ALS as are the two curvilinear bands that run parallel to the mucosal surface and intersect the radial bands. Also, there is a mottled disorganization of the internal structure of the tongue with areas of increased and decreased signal intensity.
Antibodies to GM1 and GD1b in patients with motor neuron disease without plasma cell dyscrasia
Authors: Shy Michael E. , Evans Vance A. , Lublin Fred D. , Knobler Robert L. , Heiman‐Patterson Terry , Tahmoush Albert J. , Parry Gareth , Schick Paul , Deryk Theodora G.
Published: January 2005

Fiftynine percent of 49 patients with motor neuron disease and 25% of 91 control subjects had IgM antibodies to ganglioside GM1 but usually not to GD1b at titers less than 1:80. This suggests that antibodies to GM1 may be part of the normal human antibody repertoire. However, given the higher incidence of antibodies to GM1 in patients with motor neuron disease, there may be specific epitopes important in antiganglioside antibodies associated with motor neuron disease.
Characterization of ethosuximide reduction of low‐threshold calcium current in thalamic neurons
Authors: Coulter Douglas A. , Huguenard John R. , Prince David A.
Published: January 2005

The mechanism by which ethosuximide reduces thalamic low‐threshold calcium current (LTCC) was analyzed using voltage‐clamp techniques in acutely isolated ventrobasal complex neurons from rats and guinea pigs. The ethosuximide‐induced reduction of LTCC was voltage dependent: it was most pronounced at more‐hyperpolarized potentials and did not affect the time course of activation or inactivation of the current. Ethosuximide reduced LTCC without altering the voltage dependence of steady‐state inactivation or the time course of recovery from inactivation. Dimethadione reduced LTCC by a similar mechanism, while valproic acid had no effect on LTCC. We conclude that ethosuximide reduction of LTCC in thalamic neurons is consistent with a reduction in the number of available LTCC channels or in the single LTCC channel conductance, perhaps indicating a direct channel‐blocking action of this drug. Given the importance of LTCC in thalamic oscillatory behavior, a reduction in this current by ethosuximide would be a mechanism of action compatible with the known anticonvulsant effects of this drug in typical absence seizures.
Parkinsonism and neurofibrillary tangle pathology in pigmented nuclei
Authors: Rajput A. H. , Uitti Ryan J. , Sudhakar S. , Rozdilsky B.
Published: January 2005

Four parkinsonian patients had neurofibrillary tangles, neuronal loss, and gliosis restricted to the substantia nigra and locus ceruleus. No Lewy body inclusions or other neuropathological changes accounting for parkinsonism were found in any of these patients. Their clinical features were characterized by an early age of onset, absence of dementia, absence of other neurological abnormalities, good response to drug therapy, and a long, slowly progressive course of illness. None of the patients had any history of encephalitis. These patients either represent a forme fruste of postencephalitic parkinsonism or a new entity thus far not described.
Myoclonic epilepsy and ragged‐red fibers with cytochrome oxidase deficiency: Neuropathology, biochemistry, and molecular genetics
Authors: Lombes Anne , Mendell Jerry R. , Nakase Hirofumi , Barohn Richard J. , Bonilla Eduardo , Zeviani Massimo , Yates Allan J. , Omerza Jennifer , Gales Tracy L. , Nakahara Keichi , Rizzuto Rosario , Engel W. King , Dimauro Salvatore
Published: January 2005

A 36‐year‐old man with myoclonic epilepsy and ragged‐red fibers (MERRF) died after more than 18 years of follow‐up study. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. At autopsy, there was neuronal loss and gliosis in the dentate nucleus of the cerebellum and in the inferior olivary nucleus. Skeletal muscle showed ragged‐red fibers, and paracrystalline inclusions in mitochondria by electron microscopy. Biochemical analysis showed a generalized partial defect of cytochrome c oxidase (COX) in mitochondria isolated from all tissues, including brain, heart, skeletal muscle, kidney, and liver. The Michaelis constant (Km) for cytochrome c was abnormally low, suggesting a defect of the mitochondrially encoded subunit II of COX. Immunological studies (enzyme‐linked immunosorbent assay, dot‐blot, Western blot, and immunohistochemistry) showed that the holoenzyme was decreased but subunit II was decreased more than the holocomplex or the nucleary encoded subunit IV. However, Northern and Southern blots showed that the gene for subunit II, as well as the genes for subunits I, III, IV, and VIII, were of normal size and were normally transcribed. A point mutation or a small deletion of mitochondrial DNA, probably affecting the COX‐II gene, may be responsible for the COX deficiency in this case of MERRF.
The pedunculopontine nucleus in Parkinson's disease
Authors: Zweig R. M. , Jankel W. R. , Hedreen J. C. , Mayeux R. , Price D. L.
Published: January 2005

This study demonstrated a significant loss of neurons within the lateral part of the pedunculoponite nucleus pars compacta in individuals with idiopathic Parkinson's disease and in individuals with combined Parkinson's and Alzheimer's disease. We also examined the extent of neuronal loss within the substantia nigra pars compacta, locus ceruleus, dorsal raphe nucleus, and nucleus basalis of Meynert. The number of pedunculopontine nucleus pars compacta neurons in the patients with Parkinson's or Parkinson's and Alzheimer's disease was reduced (average, 40°) in comparison with the number in control subjects or patients with Alzheimer's disease (p < 0.01). This finding correlated significantly with the extent of loss of substantia nigra pars compacta neurons (p < 0.01).
A prospective study on sudden unexpected death in epilepsy
Authors: Leestma Jan E. , Walczak Thaddeus , Hughes John R. , Kalelkar Mitra B. , Teas Shaku S.
Published: January 2005

Sudden unexpected death accounts for a substantial portion of deaths among epileptics. The incidence of this phenomenon is probably 1 in 370 to 1 in 1,110 in the general epileptic population but may be even higher in the 20‐to 40‐year age group, and still higher if epileptics with symptomatic epilepsy are selected. Sudden unexpected death in epileptics has been observed at least once weekly by the Office of the Medical Examiner of Cook County (Chicago), Illinois, for many years. A year‐long prospective study revealed that victims of this complication of epilepsy are most commonly black males averaging 35 years of age who have infrequent generalized seizures and usually have some structural lesion in the brain responsible for their seizures. They tend to abuse alcohol and have poor compliance with anticonvulsant medication. The electroencephalograms display considerable variability from record to record. At autopsy the heart, lung, and liver weights were heavier and the brain weights were lighter than expected. The mechanisms involved in sudden unexpected death in epileptics may include autonomically mediated cardiac arrhythmia alone or in combination with sudden neurogenic pulmonary edema and “backward” cardiac failure.
Perceptual‐motor and attentional correlates of developmental dysacalculia
Authors: Rosenberger Peter B.
Published: January 2005

From the patients population of a learning disorders clinic, a group of 72 relative math underachievers was selected for achievement test performance below grade level on mathematics but at or above grade level on reading, with a difference of at least 1.5 standard deviation between the two. A comparison group of 30 relative reading underachievers met the converse criteria. Neurological examination showed mixed laterality preference (right hand and foot but left eye) to be more prevalent among the math underachievers. The two groups were closely comparable on Wechsler intelligence quotient scores, although the freedom from distractibility quotient tended to be lower for the math group. The latter group also showed a lower mean achievement quotient on the Bender Visuomotor Gestalt Test. On a standard questionnaire derived from DSM‐III criteria for attention deficit disorder, the math group showed higher scores for inattention, but not for hyperactivity, impulsivity, or poor peer relations. Both perceptual‐motor and attentional deficits appear to characterize children who are specifically learning disabled for math.
Mossy fiber synaptic reorganization in the epileptic human temporal lobe
Authors: Sutula Thomas , Cascino Gregory , Cavazos Jose , Parada Isabel , Ramirez Lincoln
Published: January 2005

The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy. The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer. In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region. In nonepileptic senescent primates, occasional very sparse supragranuler Timm granules were observed that were easily distinguished from the dense pattern observed in association with human epilepsy. The results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy.
Alterations of hippocampal acetylcholinesterase in human temporal lobe epilepsy
Authors: Green Robert C. , Blume Howard W. , Kupferschmid Seth B. , Mesulam M‐Marsel
Published: January 2005

Hippocampal sclerosis is the most common pathological finding associated with human temporal lobe epilepsy. Histochemical study with acetylcholinesterase (AChE) staining was used to investigate 7 surgically resected temporal lobes with hippocampal sclerosis from patients with temporal lobe epilepsy. In all 7 specimens, an abnormal but consistent pattern of staining was noted. In the hilum of the dentate gyrus, AChE‐rich polymorphic cells were relatively preserved in comparison to the pyramidal neurons. In Ammon's horn, AChE fibers were lost in regions corresponding to the pyramidal cell dropout. AChE fibers wre also lost along the inner portion of the molecular layer of the dentate gyrus, yet they were preserved within the outer portions of the molecular layer. These findings provide additional evidence for the relative selectivity of hippocampal pathology in human temporal lobe epilepsy.
Non‐Alzheimer‐type pattern of brain cholineacetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy
Authors: Kish Stephen J. , Robitaille Yves , El‐Awar Munir , Deck H. N. , Simmons Jerry , Schut Lawrence , Chang Li‐Jan , DiStefano Linda , Freedman Morris
Published: January 2005

We recently reported reduced activity of the cholinergic marker enzyme cholineacetyltransferase (ChAT) in several brain regions of patients with dominantly inherited olivopontocerebellar atrophy (OPCA). To document the regional extent of these changes we performed a comprehensive examination of the behavior of ChAT throughout both cerebral cortical and subcortical brain areas in 5 patients from one large OPCA pedigree. As compared with the controls, mean ChAT activities in OPCA were redced by 39 to 72 in all (n = 27) cerebral cortical areas examined and in several thalamic subdivisions, caudate head, globus pallidus, red nucles, and medical olfacotry area. In contradistinction to findings in Alzheimer's disease (AD), mean ChAT levels in OPCA amygdala and hippocampal subdivisions were either normal or only mildly reduced. The lack of severe disabling dementia in our OPCA patients compared with AD patients having a similar cortical cholinergic reduction could be explained by an absence of either a marked cholinergic loss in amygdala or hippocampus or significant loss of noncholinergic cerebral cortical and limbic neurons as occurs in AD brain. We suggest that this and other OPCA pedigrees having a cortical cholinergic reduction represent a unique model for the study of behavioral consequences of a more selective cerebral cortical cholinergic lesion rather than a limbic cholinergic lesion.
Experimental autoimmune motoneuron disease
Authors: Engelhardt Jozsef I. , Appel Stanley H. , Killian James M.
Published: January 2005

An animal model of disease of the lower motoneurons has been developed by inoculating guinea pigs with bovine motoneurons. Four of 9 immunized female animals and 4 of 5 immunized male animals developed symptoms of neuromuscular degeneration marked by weakness, evidence of denervation by electromyographic and morphological criteria, and a loss of motoneurons within the spinal cord. No inflammatory foci were noted within parenchyma or meninges of the central nervous system. The immunized guinea pigs developed high serum titers of IgG class antibodies to motoneurons. Immunohistochemical studies demonstrated the presence of IgG within spinal cord motoneurons and at the end‐plates of immunized animals. This experimental autoimmune motoneuron disease may provide important insights into the cause and pathogenesis of amyotrophic lateral sclerosis, a human motoneuron disease.
Cortical dihydrophyridine binding sites are unaltered in human alcoholic brain
Authors: Kril Jillian J. , Gundlach Andrew L. , Dodd Peter R. , Johnston Graham A. R. , Harper Clive G.
Published: January 2005

The density and affinity of sites labeled by the 1, 4‐dihydrophyridines, [3H]nitrendipine and (+) [3H]PN 200‐110, were not significantly different in superior frontal and parietal cortical membranes from alcoholic patients and nonalcoholic control patients. This is in contrast to the increased number of dihydropyridine receptors and increased functional activity of calcium channels reported in brain from rats treated chronically with ethanol and in neural cell lines grown in the presence of ethanol. These results indicate that 1, 4‐dihydropyridine‐sensitive calcium channels (L type) in the brain, despite possible acute changes, are unaltered following long‐term ethanol exposure in humans.
Intermittent obstructive hydrocephalus in the Arnold‐Chiari malformation
Authors: Vrabec Tamara R. , Sergott Robert C. , Savino Peter J. , Bosley Thomas M.
Published: January 2005

A 26‐year‐old woman with a Chiari‐I malformation and intermittent symptoms of intracranial pressure elevation is described. Clinically, papilledema was accompanied by midperipheral retinal hemorrhages. Repeat computed tomographic scans and lumbar puncture showed normal results. Posterior fossa‐directed magnetic resonance image scanning revealed the Chiari‐I malformation. Intraventricular monitoring was necessary to demonstrate the marked but unsustained elevation of intracranial pressure.
Physostigmine treatment of progressive supranuclear palsy
Authors: Litvan Irene , Med Claudia Gomez , Atack John R. , Gillespie Marjorie , Kask Anne M. , Mouradian M. Maral , Chase Thomas N.
Published: January 2005

Cognitive and extrapyramidal effects of cholinomimetic therapy were evaluated in 8 patients with progressive supranuclear palsy. Each was randomized to a 10‐day double‐blind crossover trial of physostigimine and placebo. Physostigmine treatment was associated with marginal and inconsistent changes in long‐term memory, suggesting that cholinergic therapy alone is insufficient to restore cognitive function. Motor scores remained unchanged.
Selection bias in clinical trails of anaplastic glioma
Authors: Winger Michael J. , Macdonald David R. , Schold S. Clifford , Cairncross J. Gregory
Published: January 2005

We report a retrospective analysis of survival, and attrition to a study, of patients with anaplastic glioma seen at a regional cancer center during its participation in a prospective randomized clinical trial. Median length of survival for all patients was 35 weeks. Median length of survival for study patients was 60 weeks. Study patients were not representative of all patients; they were younger and less disabled than the nonstudy patients. Survival predictions for patients with anaplastic glioma based on the results of clinical trials may be overly optimistic. Many trials study a nonrepresentative subset of patients with anaplastic glioma, excluding those who do poorly at the outset and those who have poor function.
Anti–myelin‐associated glycoprotein IgM antibody titers in neuropathy associated with macroglobulinemia
Authors: Nobile‐Orazio E. , Francomano E. , Daverio R. , Barbieri S. , Marmiroli P. , Manfredini E. , Carpo M. , Moggio M. , Legname G. , Baldini L. , Scarlato G.
Published: January 2005

Twenty‐seven patients with neuropathy and IgM monoclonal gammopathy were tested for antigen specificity of the M‐protein and for anti–myelin‐associated glycoprotein (MAG) IgM levels by immunoblot. In 16 patients (59.2%) the M‐protein reacted with MAG and with cross‐reactive glycoconjugates. Anti‐MAG IgM titers in these patients ranged between 1 : 12,800 and 1 : 100,000. A fainter IgM reactivity with MAG and related glycoconjugates was detected in 3 additional patients with neuropathy, but also in 8 of 24 patients with IgM M‐protein without neuropathy (33.3%). This reactivity was not due to the M‐protein and corresponded to antibody titers of 1:400 or less in all but 1 patient with a titer of 1 : 3,200. Low titers of anti‐MAG IgM (1 : 200 or less) were also detected in 17 of 101 control patients without IgM M‐proteins (16.8%), while 1 patient with neuropathy of unknown cause had anti‐MAG IgMk titers of 1 : 25,600. In 1 patient with neuropathy and IgM M‐protein that was not anti‐MAG, the M‐protein bound to other antigens in nerve, while in 6, other possible causes or mechanisms for the neuropathy were found. In this study, high titers of anti‐MAG IgM antibodies were always associated with neuropathy. The presence of low levels of anti‐MAG IgM in a significant proportion of controls suggests that monoclonal expansion of naturally occurring B‐cell clones secreting anti‐MAG IgM may be responsible for the high incidence of this antigen specificity of the M‐protein.
Striatal dopamine deficiency in parkinson's disease: Role of aging
Authors: Scherman Daniel , Desnos Claire , Darchen François , Pollak Pierre , Javoy‐Agid France , Agid Yves
Published: January 2005

The striatal dopaminergic innervation was investigated postmortem in 49 control and 57 parkinsonian brains by assessing the binding of tritiated α‐dihydrotetrabenazine ([3H]TBZOH), a specific ligand of the vesicular monoamine transporter. The density of [3H]TBZOH binding sites in the caudate nucleus of control subjects decreased significantly with age, suggesting an age‐dependent reduction in striatal dopamine innervation. In contrast, an increase with the age at time of death was observed in patients with Parkinson's disease, although the density of [3H]TBZOH binding sites was subnormal. Mean values represented 26.5% and 12.7% of control values in the caudate nucleus and in the putamen, respectively. The binding of [3H]TBZOH in the caudate nucleus decreased exponentially with the duration of Parkinson's disease. The rate of [3H]TBZOH binding decrease, an index of the rate of striatal dopaminergic denervation, was about twice as high in parkinsonian patients as in controls and was not related to the age at onset of the disease. The data suggest that (1) parkinsonian symptoms appear above a threshold degeneration state corresponding to 50% of the normal innervation at the age of 60, and (2) aging does not play a major role in the process of nigrostriatal neuron degeneration in Parkinson's disease.
Benzodiazepine receptors and diazepam‐binding inhibitor in human cerebral tumors
Authors: Ferrarese C. , Appollonio I. , Frigo M. , Gaini S. M. , Piolti R. , Frattola L.
Published: January 2005

Benzodiazepines can regulate neoplastic growth and immune response through specific peripheral benzodiazepine receptors. We investigated the presence of peripheral and classic central benzodiazepine receptors as well as diazepam binding inhibitor, an endogenous ligand of both types of receptors, in different human cerebral tumors. Peripheral benzodiazepine receptors were present in all the tumor types studied, whereas central benzodiazepine receptors and diazepam‐binding inhibitor were detectable in astrocytomas and glioblastomas and undetectable in meningiomas, neurinomas, and metastases. The role of diazepam‐binding inhibitor and of the different benzodiazepine receptors in neoplastic cells is still to be defined.
Delayed onset of distal axonal neuropathy in primates after prolonged low‐level administration of a neurotoxin
Authors: Schaumburg H. H. , Arezzo J. C. , Spencer P. S.
Published: January 2005

Short‐latency somatosensory evoked potentials were recorded from surface electrodes overlying peripheral nerve, spinal cord, and cortex in 4 monkeys during prolonged intoxication with low levels of acrylamide. A fifth animal served as a longitudinal control subject. Slowing of the response across the spinal‐medullary junction was a reliable sign, manifest only after prolonged exposure. Associated morphological changes were preterminal accumulation of axonal neurofilaments without synaptic disruption in the gracile nucleus. The induced alterations in the latency of shortlatency somatosensory evoked potentials and in axon morphology were reversible after 7 months of recovery. The extreme delay in onset of subtle neurological dysfunction (940 days) following administration of a presumed safe level of acrylamide suggests that permissible levels of human exposure to toxins of this type should be reassessed.
Peripheral nerve disorders in instrumentalists
Authors: Lederman Richard J.
Published: January 2005

I evaluated 226 instrumentalists for playing‐related symptoms. There were 103 players (46%) of string instruments, 73 keyboard instrumentalists (32%), 44 players (19%) of wind instruments, and 6 percussionists (3%). The mean age was 32 years; 58% were women. Sixty‐five patients (29%) had a peripheral nerve disorder; 27 had symptoms of thoracic outlet syndrome; 12 had median neuropathies (carpal tunnel syndrome in 9); 9 had ulnar neuropathies; 6 had cervical radiculopathy; 5 had digital neuropathies; 3 had cranial neuropathies; and 3 had other peripheral nerve disorders. Treatment consisted of modification of playing schedules and technique, plus physical and occupational and therapy in 51 and surgical procedures in 9 patients; 5 were not treated. Follow‐up at 1 to 8 years showed 74% had a satisfactory result, 14percnt; had slight or minimal improvement, and 12percnt; had no improvement. At the time of writing, all but 4 patients remained in the music profession. It is concluded that playing‐related symptoms among instrumentalists are frequently neurological in origin and that the large majority can be helped by conservative or, on occasion, surgical means.
Positron emission tomography in manganese intoxication
Authors: Wolters E. Ch , Huang C.‐C. , Clark C. , Peppard R. F. , Okada J. , Chu N.‐S. , Adam M. J. , Ruth T. J. , Li D. , Calne D. B.
Published: January 2005

We employed 6‐fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6‐fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed.