bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis
Authors: Wiebe S. , Lee D. H. , Karlik S. J. , Hopkins M. , Vandervoort M. K. , Wong C. J. , Hewitt L. , Rice G. P. A. , Ebers G. C. , Noseworthy J. H.
Published: January 2005

Twenty‐nine mildly disabled patients with multiple sclerosis underwent serial clinical and magnetic resonance imaging (MRI) evaluations (pre‐ and postgadolinium cranial and spinal cord MRI) on at least 3 occasions at 13‐week intervals and during periods of suspected relapse. Using clinical judgment of the presence of recent active disease as the gold standard, combined MRI studies confirmed the clinical impression of active disease in 93% of follow‐up visits (sensitivity) and the absence of active MS in 63% of follow‐up visits (specificity). None of the cranial and spinal MRI‐detected abnormalities disappeared. Gadolinium administration particularly increased the yield of spinal MRI. Cranial MRI alone detected 80% of the MRI‐active visits. Clinical and MRI concordance was significantly better for the presence of recent disease activity than for the anatomical localization of the presumed site of activity. MRI evidence of apparent ongoing disease activity was seen more frequently in patients believed to have active multiple sclerosis in the preceding year (13 of 21) than in patients who had been in clinical remission for at least the 2 preceding years (2 of 8). Although clinical evidence of new disease activity was much less common in patients with active, chronic‐progressive disease (1 of 8) than in patients with active, relapsing disease (9 of 13), the proportion of patients with either infrequent relapses, frequent relapses, or slow chronic‐progressive disease in the preceding year in whom MRI activity developed and the pattern of this new MRI activity was similar between these types of active patients. This finding suggests that although there are differences in the clinical expression of disease, there may not be a fundamental difference between mild, active relapsing and mild, active progressive multiple sclerosis as defined by MRI.
Dopamine D1 and D2 receptors in progressive supranuclear palsy: An autoradiographic study
Authors: Pascual J. , Berciano J. , Grijalba B. , del Olmo E , González A. M. , Figols J. , Pazos A.
Published: January 2005

Dopamine Dl and D2 receptors were studied in brain tissue sections from a typical patient with progressive supranuclear palsy and in 7 age‐matched brains. The sensity of Dl receptors in the caudate‐putamen and fontal cortex of the patient was within control limits, By contrast, the density of nigral Dl receptors and strial D2 receptors was dramatically reduced in the patient as compared to the control brains. This work shows again that the loss of striatal D2 receptors is the most plausible explanation for the poor response to dopaminergic drugs in patients with progressive supranuclear palsy. While the loss of nigral Dl receptors can be explained by the loss of nigral neurons, it seems that neurons bearing striatal Dl receptors are spared in progressive supranuclear palsy. The clinical effects of selective D1 agonists are worth testing in this devastating disorder.
Chronic encephalitis (rasmussen's syndrome) and ipsilateral uveitis
Authors: Harvey A. Simon , Andermann Frederick , Hopkins Ian J. , Kirkham Trevor H. , Berkovic Samuel F.
Published: January 2005

Two children are reported with acute uveitis during the early progressive phase of chronic encephalitis (Rasmussen's syndrome). In both children, the side of the uveitis was ipsilateral to the side of cerebral inflammation, although in 1 child there were milder inflammatory changes in the contralateral eye. This association adds weight to the viral hypothesis of chronic encephalitis and raises the possibility of primary ocular infection and neurotropic spread to the brain.
Neurological involvement in Wegener's granulomatosis: An analysis of 324 consecutive patients at the Mayo Clinic
Authors: Nishino Hiroshi , Rubino Frank A. , DeRemee Richard A. , Swanson Jerry W. , Parisi Joseph E.
Published: January 2005

Neurological involvement in Wegener's granulomatosis was studied by reviewing the charts of 324 consecutive patients in whom the diagnosis was made at the Mayo Clinic. One hundred nine patients (33.6%) had neurological involvement. Peripheral neuropathy occured in 53; cranial neuropathy, in 21; external ophthalmoplegia, in 16; cerebrovascular events, in 13; seizures, in 10; cerebritis, in 5; and miscellaneous involvement, in 25. The mean age and sex ratio were similar in the patients with and those without neurological involvement. Among the patients with peripheral neuropathy, 42 had mononeuropathy multiplex; 6, distal symmetrical polyneuropathy; and 5, unclassified peripheral neuropathy. Multiple mononeuropathy was a major presenting symptom in 8 patients. A significantly higher percentage of patients with peripheral neuropathy, compared to those without peripheral neuropathy, had kidney involvement (p < 0.001). The second, sixth, and seventh cranial nerves were most frequently affected. Multiple cranial nerves were affected in 8 patients. Unusual neurological manifestations in the miscellaneous group were spastic paraparesis, temporal arteritis, Horner's syndrome, and papilledema.
Inherited amyloid polyneuropathy type IV (gelsolin variant) in a Japanese family
Authors: Sunada Yoshihide , Shimizu Teruo , Nakase Hirofumi , Ohta Shigeo , Asaoka Tetsuo , Amano Shiro , Sawa Mitsuru , Kagawa Yasuo , Kanazawa Ichiro , Mannen Toru
Published: January 2005

We describe a Japanese family with familial amyloid polyneuropathy type IV. The family originates from central Japan, Nagano prefecture, and is unrelated to Finnish or other Caucasian populations. Of 42 members in three generations, 14 individuals (5 men, 9 women) are affected by corneal lattice dystrophy, cranial neuropathy, mild peripheral neuropathy, and skin changes. Polarizing microscopy and immunohistochemistry studies of skin biopsy samples demonstrated abundant amyloid deposits, which bound an antigelsolin monoclonal antibody. Direct sequence analysis of a DNA fragment spanning codon 187 of plasma gelsolin complementary DNA and restriction analysis using a modified polymerase chain reaction demonstrated a single base substitution, guanine to adenine, at nucleotide position 654, which is identical to the mutation in Finnish familial amyloid polyneuropathy type IV. This strongly suggests that the mutation causes the familial amyloid polyneuropathy type IV phenotype regardless of ethnic background.
Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease
Authors: Kaler Stephen G. , Goldstein David S. , Holmes Courtney , Salerno Judith A. , Gahl William A.
Published: January 2005

Menkes disease is a neurodegenerative disorder of copper metabolism. Because the enzyme dopamine‐b̃‐hydroxylase requires copper to catalyze the conversion of dopamine to norepinephrine, we reasoned that patients with Menkes disease would have a neurochemical pattern similar to that seen in patients with congenital absence of dopamine‐b̃‐hydroxylase, i.e., high levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the catecholamine precursor dihydroxyphenylalanine (DOPA), and low levels of norepinephrine and its neuronal metabolite dihydroxyphenylglycol (DHPG). We measured plasma and cerebrospinal fluid (CSF) levels of catechols in 10 patients ranging in age from 9 days to 27 months. In contrast to patients with congenital absence of dopamine‐b̃‐hydroxylase, norepinephrine levels were normal in plasma of 4 Menkes patients and in CSF of all 10 patients. However, the ratios of DOPA : DHPG and DOPAC : DHPG in plasma and CSF of Menkes patients were invariably increased beyond the ranges of control values. These neurochemical findings indicate partial deficiency of dopamine‐b̃‐hydroxylase in Menkes patients, with compensatory increases in catecholamine biosynthesis in sympathetic nerves and in the brain. Increased tyrosine hydroxylation and increased exocytotic release of norepinephrine may be responsible for preservation of plasma and CSF norepinephrine levels in Menkes patients. The abnormal neurochemical pattern, including high ratios of DOPA : DHPG and DOPAC : DHPG, may serve as a biochemical marker for Menkes disease and provide a baseline against which the influence of proposed therapies can be judged.
Individual patterns of functional reorganization in the human cerebral cortex after capsular infraction
Authors: Willer Cornelius , Ramsay Stuart C. , Wise Richard J. S. , Friston Karl J. , Frackwiak Richard S. J.
Published: January 2005

We have previously shown bilateral activation of motor pathways and the recruitment of additional motor areas in studies of groups of patients with recovery from motor stroke. We have now deveoloped a new positron emission tomographic technique to measure the changes in regional cerebral blood flow elicated duringsd a motor task in individual patients, relative to the cerebral activatuion found in normal subjects. The patterns of cerebral activation in each of 8 individual patients with capuslar lesion of the pyramidal tract and complete recovery from hemiplegia are described by compression with the pattern found in a representative sample of 10 normal subjects. We found a large ventral extension of the hand field of the contralateral (sensori)motor cortex in all patients with lesions of the posterior limb of the internal capsule. Greater activation than in normal subjects was found in varible combination of the supplementray motor areas, the insula, the frontal operculum, and the paterial cortex. Structures belonging to motor pathways ipsilateral to the recovered limb were also more activated in the patients than in normal subjects. However, additional activation of the ipsilateral (sensori)motor cortex was only found in the 4 patients who exhibited associated movements of the unaffected hand when the recovered hand performed the motor task. We conclude that recovery from motor stroke due to striatocapsular damage is associated with individually different patterns of functional reorganization of the brain. These patterns are dependent on the site of the subcortical lesion and the somatotopicorganization of the pyramidal tract, both of which may determine the precise poetntial for recovery of limb function following this type of brain injury.
Signal loss in the motor cortex on magnetic resonance images in amyotrophic lateral sclerosis
Authors: Ishikawa Kinya , Nagura Hiroshi , Yokota Tsukasa , Yamanouchi Hiroshi
Published: January 2005

Three of 7 patients with amyotrophic lateral sclerosis had bilateral signal loss confined to the motor cortex on T2‐weighted magnetic resonance images. None of the control subjects had this abnormality. Although not present in every patient, this finding might reflect the primary pathological process of the motor cortex in amyotrophic lateral sclerosis.
Multifocal motor neuropathy: Response to human immune globulin
Authors: Chaudhry Vinay , Corse Andrea M. , Cornblath David R. , Kuncl Ralph W. , Drachman Daniel B. , Freimer Miriam L. , Miller Robert G. , Griffin John W.
Published: January 2005

Multifocal motor neuroparrhy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis, Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immue globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distral, limb weakness for 5 to 18 years, Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serun titers of anti‐GMI IgM antibody. All patients were treated with HIG, 106 to 2.4 gm/ kg., given intravenously over 3 to 5 days. Strength inproved in all patients 3 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement veried from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 to 8 patients. The serum anti‐GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conculde that HIg may be an effective therapy for patients with MMN.
Relationships between extrapyramidal signs and cognitive function in a community‐dwelling cohort of patients with Parkinson's disease and normal elderly individuals
Authors: Richards Marcus , Stern Yaakov , Mader Karen , Cote Lucien , Mayexu Richard
Published: January 2005

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community‐dwelling cohort in northern Manhattan, New York City. Fifiy‐six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke‐Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow‐up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia.
A population‐based study of multiple sclerosis in twins: Update
Authors: Sadovnick A. D. , Armstrong H. , Rice G. P. A. , Bulman D. , Hashimoto L. , Party D. W. , Hashimoto S. A. , Warren S. , Hader W. , Murrary T. J. , Seland T. P. , Metz L. , Bell R. , Duquette P. , Gray T. , Nelson R. , Weinshenkar B. , Brunt D. , Ebers G. C.
Published: January 2005

This study is a 7.5 year follow‐up of a population‐based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Cabadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8 an the dizygotic‐like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population‐based studies and to our own modified replication twin date reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These date also have importatnt implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unabiguously demonstrates the powerful effect of nonberitable factors.
Epileptic seizures after subarachnoid hemorrhage
Authors: Hassan Djo , Schonck Rob S. M. , Avezaat Cees J. J. , Tanghe Hervé L. J. , Van Gijn Jan , Lugt Paul J. M. van der
Published: January 2005

We srudied predictive factors for the occurrence of epilepsy in 381 consecutive patients admitted within 72 hours after they had a subarachnoid hemorrhage from a reprued itracranial aneursym. Fits occurring in the presence of byponattremia or within 12 hours after the initial bleed, rebleeding, or aneurysm surgery were classifed as associated with these acute events and we did not regard these fits subsequent epileptic seizures. Thirty‐five patients (9%) had one or more epileptic seizures, 12 hours to 1,761 days after the initial bleed (median value, 18 days). The following variables were included in the analysis: sex age, history of hypertension, historyof cardiovascular disease, loss of consciousness at ictus, sum score on the Glasgow Coma Scale on admission, sum score for the amount of cisternal blood and and presence of intraventricular blood based on the initial computed tomography(CT) scan, occurrence of ictal seizures (seizures occurring within 12 hours after the onset), acute hydrocephalus, rebleeding, delayed cerebral ischemia, fluid intake, treatment with tranexamic acid, ventricular drainage, and aneurysm surgery. After multivariate analysis by means of Cox proportional hazards model with stepwise forward selection of the variables, a high cisternal blood score and rebleeding proved to be significantly related to epilepsy (hazard ratio = 2.06, p = 0.040; and hazard ration = 3.02 p = 0016), even after the exclusion of 28 patients who receive perioperative prophylactic anticonvulsant therapy (hazard ratio = 2.31, P = 0.022; and hazard ratio =3.65, p = 0.006, respectively). We conclude that the frequency of epilepsy after the occurrence of subarachnoid hemorrhage is substantial and that except for rebleeding and a high cisternal blood score on the intitial CT scan, none of the investigated variables, including the occurrence of epieptic seizures within the first 12 hours following the intial bleed, are related to epilepsy.
Magnetic resonsance imaging of the cauda equina in chronic inflammatory demyelination polyneuropathy
Authors: Crino Peter B. , Grossman Robert I. , Rostami Abdolmohamad
Published: January 2005

We report a patient with biopsy proven chromic inflammatory demyelinating polyneuropathy whose magnetic resonance imaging demonstrated abnormal enhancement of the cauda equina after administration of gadolinium. Enhancement may reflect alteration of the blood‐ nerve barrier seconday to inflammation. Magnetic resonance imaging of th cauda equina could be a useful adjunct in the early diagnosis of chronic inflammatory demyelinationg polyneuropathy.
Zidovudine treatment of the AIDS dementia complex: Results of a placebo‐controlled trial
Authors: Sidtis John J. , Gatsonis Constantine , Price Richard W. , Singer Elyse J. , Collier Ann C. , Richman Douglas D. , Hirsch Martin S. , Schaerf Frederick W. , Fischl Margaret A. , Kieburtz Karl , Simpson David , Koch Matthew A. , Feinberg Judith , Dafni Urania ,   The Aids Clinical Trials Group
Published: January 2005

The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double‐blinded, placebo‐controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16‐week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.
Analysis of autoantibody binding to 52‐kd paraneoplastic cerebellar degeneration–associated antigen expressed in recombinant proteins
Authors: Sakai Koichiro , Ogasawara Tomoko , Hirose Genjiro , Jaeckle Kurt A. , Greenlee John E.
Published: January 2005

A 52‐kd neural antigen was reported to be recognized by anti‐Purkinje cell antibodies in serum of a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. In this study, we demonstrate that this neural antigen is recognized by antibodies known as anti‐Purkinje cell antibody type I (PCAb Type I) and anti‐YO. The latter's antigen is reported to be specific for the 62‐ to 64‐kd antigen CDR62. Assuming that the 52‐kd and 62‐ to 64‐kd antigens share a common epitope(s) recognized by all of these antibodies, we examined the antigenic region on the 52‐kd protein by immunoblots with deletion fragment proteins of the recombinant 52‐kd protein. A major epitope was localized in the region of amino acid residues 94 to 133 of the 52‐kd protein, which is the site of a leucine zipper motif. The potential pathogenicity of PCAb Type I is discussed.
The clinical and topographic spectrum of cerebellar infarcts: A clinical—magnetic resonance imaging correlation study
Authors: Barth A. , Bogousslavsky J. , Regli F.
Published: January 2005

We studied 34 consecutive patients with non–mass‐producing cerebellar infarcts using a standard protocol of investigations including magnetic resonance imaging (MRI). We analyzed the topography of infarcts to determine the involved arterial territories and we correlated the findings with neurological dysfunction and potential causes of stroke. Sixteen patients had an infarct in the territory of the posterior inferior cerebellar artery (PICA); 2, in the territory of the anterior inferior cerebellar artery (AICA); 13, in the territory of the superior cerebellar artery (SCA); and 8 had junctional infarcts between the territories of the medial and lateral branches of the PICA or PICA/SCA territories. PICA or medial PICA territory infarcts were manifested by acute vertigo and truncal ataxia, while the patients with lateral PICA territory infarcts presented with unsteadiness, limb ataxia and dysmetria without dysarthria. Patients with infarcts in the AICA territory were characterized by limb and trunk ataxia associated with signs of lateropontine involvement. Patients with SCA territory infarcts presented with dysarthria, unsteadiness and/or vertigo, limb ataxia, and dysmetria. Cardiac embolism was the main cause of large infarcts in the territories of the PICA (8/16) or SCA (4/7). Multiple small infarcts were associated with vertebrobasilar atherosclerosis (8/12). These clinical–MRI correlations allow better definition of the topographic and etiological spectrum of cerebellar infarction, which was previously based on pathological studies in subjects with severe infarction.
Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease
Authors: Eidelberg D. , Takikawa S. , Moeller J. R. , Dhawan V. , Redington K. , Chaly T. , Robeson W. , Dahl J. R. , Margouleff D. , Fazzini E. , Przedborski S. , Fahn S.
Published: January 2005

Regional and global metabolic rates for glucose were estimated using 18F‐fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 ± 6.9 years; mean disease duration, 4.7 ± 2.2 years; mean Hoehn and Yahr score, 3.5 ± 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age‐matched normal volunteers, 10 disease severity–matched patients with Parkinson's disease(PD), and 10 disease duration–matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate(p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitaive ratings of motor disability (p < 0.02). These results suggest that quantitative 18F‐fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions.
Clinical determinants of dememtia related to stroke
Authors: Tatemichi T. K. , Desmond D. W. , Paik M. , Figueroa M. , Gropen T. I. , Stern Y. , Sano M. , Remien R. , Williams J. B. W. , Mohr J. P. , Mayeux R.
Published: January 2005

Among 251 patients examined 3 months after the onset of acute ischemic stroke, we diagnosed dementia in 66(26.3%) by using modified DSM‐III‐R criteria based on neuropsychological, neurological, functional, and psychiatric examinations. We uses a logistic regression model to derive odds rations(ORs) for clinical factors independently related to dementia in this cross‐sectional sample. Dementia was significantly associated with age, education, and race. A history of prior stroke (OR= 2.7) and diabetes mellitus (OR=2.6) was also independently related to dementia, but hypertension and cardiac disease were not. Stroke fearures associated with dementia included lacunar infarction compared with all other subtypes combined (OR=2.7) was also independently related to dementia, but hypertension and cardiac disease were not. Stroke features associated with dementia included lacunar infarction compared with all other subtypes combined (OR= 2.7) and hemisphetic laterality in relarion to brainstem or cerebellar location. There was a predominance of dementia in patients with left‐sided lesions(Or‐4.7), an effect not explained by aphasis. Dementia was especially common with infarctions in the left posterior cerebral and anterior cerebral artery territories. A major dominant hemispheral syndrome (reflecting size and laterality) was also independently associated with dementia (OR=3.9). We suggest that dementia after ischemic stroke is a result of multiple independent factors, including both small subcrtical and large cortical infarcts especially involving the left medial frontal and temporal regions, with additional contributions by demographic and vascular risk factors.
Elevated serum levels of tumor necrosis factor‐α in Guillain‐Barré syndrome
Authors: Sharief M. K. , McLean B. , Thompson E. J.
Published: January 2005

Activated T lymphocytes and macrophages play a putative role in the pathogenesis of Guillian‐Barré syndrome. Both cell types secrete tumor necrosis factor‐α, a cytokine that has well‐recognized toxi effects on myelin, Schwann cells, and endothelial cells. We determined serum and cerebrospinal fluid concentrations of tumor necrosis factor α in 26 patients with Guillain‐Barré syndrome, 27 patients with other polyneuropathies, 30 patients with neurological diseases of the central nervous system, and 14 helthy control subjects. Markedly increased serum levels were detected in 14 patients(54%) with Guillian‐Barré syndrome and to a significantly lesser extent, in patients with other polyneuropathies (26%) and in neurological control subjects(23%). Tumor necrosis factor‐α was not detected in the cerebrospinal fluid of patients with Guillain‐Barré syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain‐Barré syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain‐Barré syndrome correlated directly with disease severity and these concentrations returned to normal in parallel with clinical recovery. These findings emphasize the complexity of the immune response in patients with Guillain‐Barré syndrome and suggest that tumor necrosis factor‐αL may be important in the pathogenesis of peripheral demylination in this disorder.
The Golgi apparatus of moptor neurons in amyotrophic lateral sclerosis
Authors: Mourelatos Zissims , Yachnis Anthony , Rorke Lucy , Mikol Jacqueline , Gonatas Nicholas K.
Published: January 2005

The Golgi apparatus plays a key role in the posttranslational processing of ploypeptides destined for secretion, incorporation into plasma memberanes, and fast axoplasmic transport. Dispersion of fragmentation of the Golgi apparatus, experimentally induced by microtuble‐disrupting agents, is associated with decreased secretion of immunoglobulins and insulin. The golgi apparatus is also involved in targeting of lysosomal enzymes and in the endocytosis of certain hormones, receptors, and toxins. There is a paucity of information on this important organelle in human neuropathological conditions. Using an organelle‐specific antiserum we have examined by immunocytochemistry the Golgi apparatus of motor neurons in the spinal cord in 4 patients with amyotrophic lateral sclerosis and 1 patient with Werding Hoffmann's disease, I with infantile neuronal degeneration, 1 with adult‐type familial bulbospinal atrophy, I with motochondrial myopathy with cytochrome c oxidase deficiency, 1 with centronuclear myopathy, and 1 with Duchenne'smuscular dystrophy, and in 9 age‐matched control subjects. In all motor neuronopathies examined and in the patient with mitochondrial myopathy, 20 to 85% of neurons counted had “fragmented” golgi apparatus. In age‐matched control subjects and the other 2 patients with myopathies, 0 to 1.65% of motor neurons had fragmented Golgi apparatus. These findings suggest that the Golgi apparatus of motor neurons is involved in patients with amyotrophic lateral sclerosis and relation motor neuron diseases, and perhaps in patients with certain fatal primary myopathies.
Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis
Authors: Page William F. , Durtzke John F. , Murphy Frances M. , Norman James E.
Published: January 2005

Self‐reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state‐by‐state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancesty is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non‐Scandinavian correlations may effect predomininatly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural evironment, is part of the complicated picture of MS as a disease of place.
A positron emission tomography study of essential tremor: Evidence for overactivity of cerebellar connections
Authors: Jenkins I. H. , Bain P. G. , Colebatch J. G. , Thompson P. D. , Findley L. J. , Frackowiak R. S. J. , Marsden C. D. , Brooks D. J.
Published: January 2005

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.
The spectrum of immune responses to Campylobacter jejuni and glycoconjugates in Guillain‐Barré syndrome and in other neuroimmunological disorders
Authors: Enders Uwe , Karch Helge , Toyka Klaus V. , Michels Marco , Zielasek Jürgen , Pette Martin , Heesemann Jürgen , Hartung Hans‐Peter
Published: January 2005

An acute infectious illness frequently precedes the Guillain‐Barré syndrome. Recently, Campylobacter jejuni was claimed to be a predominant precipitating agent that may also trigger a humoral immune response to glycoconjugates of peripheral myelin in Guillain‐Barré syndrome. Because of conflicting reports, we determined the frequency of a recent infection with C. jejuni in 38 patients with Guillain‐Barré syndrome using a highly sensitive and specific immunoblot technique, and of the presence of circulating antibodies to gangliosides. We detected IgM and/or IgG C. jejuni directed antibodies in 15 of 38 patients with Guillain‐Barré syndrome. In contrast, only 7 of 39 healthy control subjects, 3 of 20 patients with multiple sclerosis, and 2 of 72 patients with neuroborreliosis showed IgA or IgM antibody responses to C. jejuni. In Guillain‐Barré syndrome, C. jejuni–specific antibodies were predominantly directed to outer membrane proteins of one specific serotype, Lior 11, whereas the most common serotype associated with enteritis in Germany is Lior 4. Two of 27 patients with Guillain‐Barré syndrome had ganglioside‐specific IgA antibodies; 1 of 32 patients, antibodies of IgM; and 4 of 31 patients, antibodies of IgG class. There was no correlation between severity, type (axonal versus demyelinating), and outcome of the disease and the presence or absence of a humoral immune response to C. jejuni or to glycoconjugates. Our findings do not support previous suggestions that a preceding C. jejuni infection heralds a poorer outcome or that antibodies to gangliosides carry prognostic significance. The predilective humoral immune response to outer membrane proteins of one specific C. jejuni serotype raises new important questions concerning the immunopathogenic link between an acute C. jejuni infection and subsequent Guillain‐Barré syndrome.
Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM‐1
Authors: Archelos Juan J. , Jung Stefan , Mäurer Mathias , Schmied Mascha , Lassmann Hans , Tamatani Takuya , Miyasaka Masayuki , Toyka Klaus V. , Hartung Hans‐Peter
Published: January 2005

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by active immunization with myelin from guinea pig spinal cord by the encephalitogenic myelin basic protein or by adoptive transfer using myelin basic protein‐specific CD4‐positive T cells. Treatment with purified monoclonal antibody (1A‐29) to the intercellular adhesion molecule‐1 and its F(ab')2 fragments efficiently suppressed active EAE. Control treatment with an irrelevant antibody or saline did not alter the course of the disease. Histological sections of the central nervous system showed a pronounced reduction of inflammatory infiltrates during treatment with antibody to intercellular adhesion molecule‐1. In the adoptive transfer model of EAE, 1A‐29 had only a minor effect. Proliferation assays on lymph node cells ex vivo from 1A‐29– and saline‐treated animals were performed. Administration of 1A‐29 suppressed antigen‐specific T‐cell proliferation. The differential effects in EAE versus adoptive transfer EAE suggest that 1A‐29 acts predominantly on the induction phase of the immune response and, to a lesser extent, on the transendothelial migration of T cells. We conclude that intercellular adhesion molecule‐1–dependent pathways are critically involved in the pathogenesis of EAE and that antibodies to leukocyte adhesion molecules could be a novel therapeutic approach to autoimmune disease of the central nervous system.
Abnormal eye movements in Creutzfeldt–Jakob disease
Authors: Grant Michael P. , Cohen Mark , Petersen Robert B. , Halmagyi G. Michael , McDougall Alan , Tusa Ronald J. , Leigh R. John
Published: January 2005

We report 3 patients with autopsy‐proven Creutzfeldt–Jakob disease who, early in their course, developed abnormal eye movements that included periodic alternating nystagmus and slow vertical saccades. These findings suggested involvement of the cerebellar nodulus and uvula, and the brainstem reticular formation, respectively. Cerebellar ataxia was also an early manifestation and, in 1 patient, a frontal lobe brain biopsy was normal at a time when ocular motor and cerebellar signs were conspicuous. As the disease progressed, all saccades and quick phases of nystagmus were lost, but periodic alternating gaze deviation persisted. At autopsy, 2 of the 3 patients had pronounced involvement of the cerebellum, especially of the midline structures. Creutzfeldt‐Jakob disease should be considered in patients with subacute progressive neurological disease when cognitive changes are overshadowed by ocular motor findings or ataxia.
Human immunodeficiency virus type 1 infections and myopathy: Clicical relevance of zidovudine therapy
Authors: Grau Josep M. , Masanés Ferrán , Pedrol Enric , Casademont Jordi , Fernández‐Solá Joaquim , Urbano‐Márquez Alvaro
Published: January 2005

Fifty consecutive patients infected with human immunodeficiency virus type 1 (HIV‐1) were evaluated regarding the prevalence of HIV‐related myopathies and the relevance of zidovudine‐related mitochondrial myopathy. Disease stage, total lifetime intake of zidovudine, anthropometric and nutritional parameters, muscle strength, and histochemical and immunohistochemical findings in muscle specimens were recorded. The series was divided into two groups, patients with a total lifetime intake of zidovudine under 200 gm and those with a total lifetime intake over 200 gm. A control group included 50 healthy people matched for age and sex. HIV‐related myopathy was defined by the presence of at least one of the classic pathological reactions in muscle, while idovudine‐related myopathy was defined by the presence of raged red fibers in any percentage. Lower values of the nutritional parameters were detected in the HIV cohott, when compared with normal control values. HIV‐related myopathy was detected in 13 (26%) of the 50 patients. There were no differneces between groups except for the development of mitochondrial myopathy that occurred in 1 of the 26 patients in Group I and in 16 of the 24 in Group II. Six patients who had a total intake of more than 200 gm of zidovudine and demonstrated red ragged fibers in their muscle speciments were absolutely asymptomatic. There was a positive correlation between total intake of zidovudine and the percentage of red ragged fibers in muscle biopsy specimens.
Human positron emission tomographic [18F]Fluorodopa studies correlate with dopamine cell counts and levels
Authors: Snow B. J. , Tooyama I. , McGeer E. G. , Yamada T. , Calne D. B. , Takahashi H. , Kimura H.
Published: January 2005

Postmortem counts of dopaminergic cell densities in the substantia nigra (5 subjects) and striatal levels of dopamine (DA) and its metabolites (6 subjects) were determined on 1 parkinsonian (PD), 3 progressive supranuclear palsy (PSP), 1 amyotrophic lateral sclerosis, and 1 Alzheimer's case who had been positron emission tomography scanned with 6‐[18F]fluorodopa during life. [18F]Fluorodopa uptake rate constants, which presumably depend on the number of functioning striatal DA terminals, were strictly proportional to cell densities (significant correlation with zero intercept) and also correlated significantly with striatal DA levels but with an intercept indicating greater losses of DA than of terminals in PSP and PD. Postmortem data on 6 PD, 1 PSP, and 9 neuronally normal controls substantiated the significant correlation between cell counts and DA levels, with the latter being the more depressed in pathological cases.
Functional integration of cortical grafts placed in brain infarcts of rats
Authors: Grabowski M. , Brundin P. , Johansson B. B.
Published: January 2005

Five to 6 days after a right middle cerebral artery occlusion, a cell suspension of fetal neocortex was grafted into the infarcted area of adult spontaneously hypertensive rats. Three to 17 months later, functional integration of the grafts into the afferent somatosensory pathway was tested using the 2‐[14C]deoxyglucose method for estimation of glucose utilization. Grafted rats (n = 8) and control rats (n = 5) with no arterial occlusion were stimulated in the left vibrissal region resulting in an increased glucose utilization in the left trigeminal sensory nucleus and the right ventroposterior nucleus of the thalamus, whereas the same regions in a group (n = 5) of nonstimulated grafted rats were not activated. Glucose uptake in the right somatosensory cortex of control rats was 96 ± 5 (mean ± SEM) μmol/100 gm/min. Neocortical grafts consumed less glucose than cortex in control rats but the vibrissae‐stimulated group displayed a 110% higher value than the nonstimulated grafted group (32 ± 5 vs 15 ± 2, p < 0.05). We conclude that graft glucose metabolism is increased following stimulation of the host somatosensory pathway, which demonstrates that transplanted neurons can be functionally integrated with neural circuitries of the host after an ischemic insult.
The T‐cell response to myelin basic protein in familial multiple sclerosis: Diversity of fine specificity, restricting elements, and T‐cell receptor usage
Authors: Joshi Narendra , Usuku Koichiro , Hauser Stephen L.
Published: January 2005

Indirect evidence suggests that an autoimmune response to myelin basic protein (MBP) may be involved in the pathogenesis of multiple sclerosis (MS). In MS, several reports have suggested that restricted T‐cell populations respond to MBP, as in inbred rodents with the MS disease model experimental allergic encephalomyelitis. In experimental allergic encephalomyelitis, the T‐cell repertoire to MBP varies between strains, and in MS it is likely that the response to MBP is also best defined under conditions where genetic differences between subjects are controlled. In this report, the fine specificity of the T‐cell response to MBP was assessed in three families, each with multiple individuals affected with MS. We found that (1) comparable frequencies of MBP‐reactive T‐cell lines were obtained from peripheral blood of MS patients and their healthy siblings. Human leukocyte antigen (HLA) identical sibling pairs discordant for MS had similar frequencies of MBP‐reactive T‐cell lines. (2) A broad spectrum of MBP epitopes was recognized by T‐cell lines from all individuals studied. Within a family, the fine specificity of MBP recognition showed little or no overlap between individuals, even between HLA identical siblings. (3) Recognition of MBP epitopes occurred in the context of different HLA class II alleles. At least four DR alleles each served as restricting elements for recognition of P82—101 or the carboxy terminal region of MBP, two regions thought to be important in the human T‐cell response to the molecule. No relationship between the use of a particular DR allele and a response to a particular region of MBP could be established. (4) Apparently random expression of different T‐cell receptor Vβ gene families by MBP‐reactive T‐cell lines was present, with little overlap by different lines reponding to the same region of MBP, or between different individuals belonging to the same family. These results demonstrate that the frequency and fine specificity of T‐cell responses to MBP in peripheral blood is independent of the MS phenotype.
Failure of 3,4‐diaminopyridine to reverse conduction block in inflammatory demyelinating neuropathies
Authors: Bergin Peter S. , Miller David H. , Hirsch Nicholas P. , Murray Nicholas M. F.
Published: January 2005

3,4‐Diaminopyridine was administered to 6 patients with inflammatory demyelinating neuropathies in whom partial conduction block was demonstrable. Four had Guillain‐Barré syndrome and 2 had chronic inflammatory demyelinating neuropathy. Nerve conduction studies were performed before the administration of a single oral dose of 3,4‐diaminopyridine, and at regular intervals thereafter. Neither resolution of conduction block nor clinical benefit were seen.
Positron emission tomographic imaging of the dopamine transporter with 11C‐WIN 35,428 reveals marked declines in mild Parkinson's disease
Authors: Frost J. James , Rosier Annemie J. , Reich Stephen G. , Smith Justin S. , Ehlers Michael D. , Snyder Solomon H. , Ravert Hayden T. , Dannals Robert F.
Published: January 2005

Parkinson's Disease (PD) is characterized by a selective loss of nigrostriatal dopaminergic neurons that results in a marked reduction of dopaminergic nerve terminals in the striatum. Recently, 11C‐WIN 35,428, a cocaine analogue that specifically labels the dopamine transporter, was developed and can be used to label dopaminergic nerve terminals in vivo by positron emission tomography. In healthy control subjects, binding of 11C‐WIN 35,428 is highest in the striatum. In addition, 2 symmetrical focal areas of low binding were observed in the midbrain. The cerebellum functioned as an appropriate region for nonspecific binding. The binding of 11C‐WIN 35,428 in patients with PD (Hoehn‐Yahr II) was compared with that in healthy control subjects by using the (region‐cerebellum)/cerebellum ratio for data acquired 34 to 82 minutes after injection. In control subjects, this ratio varied, at approximately 2, in the striatum. In patients with PD, binding in the posterior putamen was reduced by 78%, whereas the anterior putamen and the caudate nucleus showed a reduction of 59 and 39%, respectively. The reduction in 11C‐WIN 35,428 binding was highest in the midbrain (84%). The high specific/nonspecific binding ratio and the pronounced reduction in binding in mild PD may permit detection of even earlier stages of PD or presymptomatic individuals with dopaminergic cell loss.
Ictal single‐photon emission computed tomography demonstrates localized epileptogenesis in cortical dysplasia
Authors: Kuzniecky Ruben , Mountz James M. , Wheatley Gregory , Morawtz Richard
Published: January 2005

We investigated the use of ictal single‐photon emission computed tomography (SPECT) in 2 children with intractable epilepsy. Ictal scalp electroencephalographic studies failed to localize the epileptic focus and interictal data demonstrated widespread lateralized abnormalities. Ictal SPECT studies with technetium 99m–hexamethylpropyleneamineoxime demonstrated focal areas of hyperperfusion in the frontal lobes. Resection of the abnormal areas shown by SPECT was carried out despite evidence of large areas of epileptogenesis demonstrated by scalp and subdural electroencephalographic studies. Pathological material revealed cortical dysplasia. Ictal SPECT provides functional evidence for localized epileptogenesis in focal cortical dysplasia.