bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of patients with multiple sclerosis by evoked potentials and magnetic resonance imaging: A comparative study
Authors: Cutler John R. , Aminoff Michael J , Brant‐Zawadzki Michael
Published: January 2005

We compared the diagnostic usefulness of evoked potential (EP) studies and magnetic resonance imaging (MRI) in the evaluation of 27 patients with definite or probable multiple sclerosis (MS). MRI scans demonstrated multiple lesions in 21 patients whereas EP studies showed multiple abnormalities in 14 patients (4 of whom had only somatosensory EP abnormalities). Eighteen patients has similar MRI and EP results (e.g., normal or multiple abnormalities), 8 had multiple abnormalities shown by MRI but normal or single‐modality abnormal EPs, and 1 had multiple abnormal EPs but a normal MRI scan. There was no significant difference in the sensitivity of the two techniques in detecting multiple lesions in the patients with definite MS, whereas among those with probable MS, MRI had a significantly higher yield. Seventeen patients showed clinical evidence of posterior fossa involvement, 6 patients had abnormal brainstem auditory evoked potentials (BAEPs), and 4 patients had areas of increased signal intensity revealed by MRI of the brainstem. There was no clinical evidence of brainstem involvement in 2 patients with BAEP abnormalities, 2 with an abnormal posterior fossa shown by MRI, and one patient with abnormalities shown by both BAEP and MRI. We conclude that MRI is more sensitive in detecting multiple lesions than are multimodality EP studies, but that BAEP assessment may be slightly more sensitive than MRI in detecting brainstem lesions.
The lennox‐gastaut syndrome: Metabolic subtypes determined by 2‐deoxy‐2 [18F]fluoro‐d‐glucose positron emission tomography
Authors: Chugani Harry T. , Mazziotta John C. , Engel Jerome , Phelps Michael E.
Published: January 2005

We employed positron emission tomography (PET) with 2‐deoxy‐2[18F]fluoro‐D‐glucose (FDG) to study local cerebral glucose utilization in 15 children who had Lennox‐Gastaut syndrome. Our results show that LGS can be classified into four predominant subtypes, each with a distinct metabolic pattern: (1) unilaterla focal hypometabolism, (2) unilateral diffuse hypometabolism, (3) bilateral diffuse hypometabolism, and (4) normal. Functional disturbances seen on FDG‐PET did not always correlate with abnormalities revealed by x‐ray computed tomographic scan. This classification of Lennox‐Gastaut syndrome into four major metabolic subtypes not only provides a new perspective toward understanding cerebral function in this complex syndrome, but may also prove useful in the clinical management of these patients.
Risk factors for complex partial seizures: A population‐based case‐control study
Authors: Rocca Walter A. , Sharbrough Frank W. , Hauser W. Allen , Annegers John F. , Schoenberg Bruce S.
Published: January 2005

This investigation is to our knowledge the first population‐based case‐control study of risk factors for complex partial seizures (CPS). Included in the study were all patients with onset of complex partial seizures before age 35, who were residents of Rochester, Minnesota, at the time of diagnosis between 1935 and 1979, and who were also born in Rochester (n = 82). Two control subjects were matched to each patient, and for both patients and control subjects, the unique records‐linkage system for residents of Rochester was used to obtain information about possible risk factors. A history of epilepsy or febrile seizures in the mother, febrile seizures, neonatal convulsions, cerebral palsy, head trauma, and viral encephalitis were significantly more common in patients than in control subjects (p < 0.05). None of the prenatal or perinatal factors investigated were found to be associated with complex partial seizures, except for being small for gestational age at birth. This factor lost significance after adjustment for cerebral palsy.
GABA‐mimetic drugs enhance apomorphine‐induced contralateral turning in rats with unilateral nigrostriatal dopamine denervation: Implications for the therapy of Parkinson's disease
Authors: Bennett James P. , Ferrari Marina B. , Cruz C. Joseph
Published: January 2005

The underlying mechanisms responsible for advanced Parkinson's disease's becoming refractory to dopamimetic therapies are unclear. Postmortem brain studies indicate that patients with Parkinson's disease have decreased basal ganglia γ‐aminobutyric acid (GABA) function in addition to profound striatal dopamine (DA) deficiencies. In experimental animals, GABA‐utilizing striatal and nigral projection neurons appear to mediate motor behaviors arising from the stimulation of striatal DA receptors by agonists. We have examined the ability of directly and indirectly acting GABA‐mimetic drugs to alter turning behavior elicited by administering apomorphine, a DA agonist, to rats with unilateral lesions of dopaminergic nigrostriatal neurons. Low doses of directly acting postsynaptic GABA agonists (progabide, 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin—3‐01) or a neuronal GABA transport inhibitor (SKF 100330‐A) potentiate apomorphine‐induced turning. Higher doses of these agents or acute inhibition of GABA catabolism inhibits turning. Our results suggest that low doses of certain GABA‐mimetics will improve the responses of patients with Parkinson's disease to concurrent DA receptor agonist therapy.
Tabacco‐induced primary‐position upbeat nystagmus
Authors: Sibony Patrick A. , Evinger Craig , Manning Karen A.
Published: January 2005

The effects of tobacco smoking on the eye movements of normal human subjects were studied using direct current electrooculography and the magnetic search coil technique. Tobacco induced a transient primary‐position upbeat nystagmus in the dark, which was suppressed by visual fixation. It obeyed Alexander's law and was associated with oblique upward fast phases that alternated from side to side. Tobacco‐induced nystagmus exhibited a latency of onset at 40 to 90 seconds, a duration of 10 to 20 minutes, and maximum slow‐phase velocities at 2 to 3 minutes. We suggest that tobacco induces primary‐position upbeat nystagmus through the excitatory effects of nicotine on the central vestibular pathways.
Type 1 human poliovirus binds to human synaptosomes
Authors: Brown Robert H. , Johnson David , Ogonowski Mark , Weiner Howard L.
Published: January 2005

Poliovirus is a neurotropic virus that selectively infects human motoneurons in vivo. The basis for the specificity of this infection is not fully understood. It has been suggested that this tropism occurs because motoneurons are the only neurons to express poliovirus receptors. We have examined this hypothesis by measuring the binding of 125I‐labeled poliovirus type 1 to neural tissues. With this assay we have detected highly specific binding sites in human but not rodent neural tissue. Regional assays of binding in human central nervous system homogenates demonstrate that binding sites are not confined to motoneurons. Rather, they are widely distributed throughout the human neuraxis. Particularly in the forebrain, binding is more abundant in gray than white matter. For this reason, we performed tissue fractionation studies which indicate that poliovirus binding sites are enriched in synaptosomes, the subfraction of central nervous system gray matter tissue rich in synaptic endings. The preferential expression of poliovirus binding sites in synaptic endings may be an important factor in the motor tropism of this virus, inasmuch as the major category of neurons with synaptic endings outside the central nervous system are motoneurons; thus, particles of virus may preferentially bind to this cell type during poliovirus viremia.
Electrophysiological dfierences between demented and nondemented patients with Parkinson's disease
Authors: Goodin Douglas S. , Aminoff Michael J.
Published: January 2005

Long‐latency auditory evoked potentials were studied in demented and nondemented patients with Parkinson's disease who were matched for age, stage of disease, duration of illness, and amount and nature of antiparkinsonian medication. We found clear electrophysiological differences between the two groups of patients in that the N1, N2, and P3 peak latencies were prolonged in the demented group compared both to the nondemented group and to normal controls. Moreover, the N1 latency but not the N2 and P3 latency prolongation distinguished the demented parkinsonian patients from demented patients with Alzheimer's disease. These results provide strong evidence for the existence of different subtypes of dementia and suggest that electrophysiological recordings may be helpful in establishing the underlying pathogenesis of a dementia syndrome when there is clinical uncertainty.
Deficiency of a cholinergic differentiating factor in fibroblasts of patients with Alzheimer's disease
Authors: Kessler John A.
Published: January 2005

Skin fibroblasts from patients with Alzheimer's disease and from apparently normal control subjects were compared for their production of a cholinergic differentiating factor. The factor's activity was assayed by measuring the induction of choline acetltransferase (CAT) activity in cultured sympathetic neurons. Culture medium conditioned by exposure to normal human fibroblasts induced substantial levles of CAT activity in sympathetic neurons, indicating that human fibroblasts produce a soluble factor that promotes cholinergic expression. In contrast, medium conditioned by Alzheimer fibroblasts induced only about one‐third as much CAT activity, a highly significant reduction (p < 0.01). These observations suggest that Alzheimer fibroblasts may be deficient in their secretion of a cholinergic factor and raise the possibility that the pathophysiology of the disease is related to a defect in the release of this factor. The fibroblast abnormalities suggest that Alzheimer's disease may be a systemic disease involving nonneuronal cells that are outside as well as within the brain.
Caloric‐induced nystagmus with isoelectric electroencephalogram
Authors: Nayyar Manmohan , Strobos Robert J. , Singh Brij M. , Brown‐Wagner Marie , Pucillo Anthony
Published: January 2005

Caloric vestibular testing induced nystagmus in a patient with an isoelectric electroencephalogram after cardiopulmonary arrest. This has been demonstrated previously in patients in a chronic persistent vegetative state with intact brainstem reflexes, but never in a patient with an isoelectric electroencephalogram. Animal studies indicate that the quick phase of nystagmus and horizontal saccades are generated in the paramedian pontine reticular formation. The present case supports the conclusion that caloric‐induced nystagmus originates in the brainstem in rudimentary form.
Chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy
Authors: McCombe P. A. , McManis P. G. , Frith J. A. , Pollard J. D. , McLeod J. G.
Published: January 2005

In a series of 61 patients with the relapsing variety of chronic inflammatory demyelinating polyneuropathy, there were 16 women of childbearing age, 9 of whom became pregnant. In 4 of these women, the onset of neuropathy occurred in pregnancy and in the other 5 relapses occurred during pregnancy. These was a significant increase in the number of relapses during the year of pregnancy, and a tendency for symptoms to worsen during the third trimester or immediate postpartum period. It is concluded that there is an increased risk of relapse of chronic inflammatory demyelinating polyneuropathy in pregnancy.
Whipple's disease confined to the central nervous system
Authors: Adams Melanie , Rhyner Patricia A. , Day John , DeArmond Stephen , Smuckler Edward A.
Published: January 2005

Progressive hypersomnia, memory disturbance, and vertical ophthalmoplegia developed in a 63‐year‐old woman. The diagnosis of Whipple's disease of the central nervous system was suggested by her presentation and results of studies using magnetic resonance imaging. Despite a one‐month course of antibiotics, active Whipple's disease, localized to the central nervous system, was found at autopsy.
Chronic progressive myelopathy associated with elevated antibodies to human T‐lymphotropic virus type I and adult T‐cell leukemialike cells
Authors: Osame Mitsuhiro , Matsumoto Makoto , Usuku Koichiro , Izumo Shuji , Ijichi Naomi , Amitani Hiroyoko , Tara Mitsutoshi , Igata Akihiro
Published: January 2005

Six adult patients had a chronic progressive myelopathy that possessed the following features: (1) high antibody titers to human T‐lymphotropic virus type I (HTLV‐I) in serum and cerebrospinal fluid (CSF); (2) predominantly upper motor neuron disorder, symmetrical, with mild sensory and bladder disturbances; and (3) presence of adult T‐cell leukemia–like cells in both peripheral blood and CSF. We refer to this entity as HTLV‐I–associated myelopathy (HAM). Electrophoretic studies of immunoglobulin G in CSF using Western blot analysis characteristically demonstrated p24 and p32 bands. Rates of intra‐blood–brain barrier synthesis were determined and found increased in the patients with HAM. Corticosteroid treatment produced clinical improvement in all of 4 patients. A retrospective survey of CSF samples was carried out in 287 patients with neurological disorders, and 6 additional patients with HAM were identified.
Sardinia, a high‐risk area for multiple sclerosis: A prevalence and incidence study in the district of alghero
Authors: Rosati Giulio , Aiello Isidoro , Pirastru Maria I. , Mannu Luisella , Demontis Giuseppe , Becciu Sebastiano , Sau Gianfranco , Zoccheddu Alberto
Published: January 2005

Findings from small descriptive studies carried out in the last few years in Sardinia suggest that this region is now of high rather than medium risk for multiple sclerosis. It is uncertain whether this high prevalence reflects a different approach in case finding over time or a true change in disease occurrence. We report the results of a prevalence and incidence survey conducted in the district of Alghero, a community of 78,000 people in northwest Sardinia. Based on data from 31 patients, the average annual incidence for the period 1971 through 1980 was 4.1 per 100,000. On December 31, 1980, the prevalence rate was 59 per 100,000. The results support the view that Sardinia is now a high‐risk area for multiple sclerosis, and further suggest a rise in the occurrence of the disease in recent years.
Generation of human B‐cell hybridomas secreting monoclonal anti–myelin‐associated glycoprotein antibodies from a patient with neuropathy
Authors: Spatz Linda , Lieberson Becky , Abraham Judith , Miller Orlando J. , Miller Dorothy A. , Latov Norman
Published: January 2005

Human hybridomas that secrete monoclonal IgM anti–myelin‐associated glycoprotein antibodies were generated by fusion with cells from a patient with peripheral neuropathy and IgM monoclonal gammopathy. Karyotypic analysis of the hybridoma cells revealed no chromosomal abnormalities. The cells were positive for cell‐surface idiotype HLA‐DR and the plasma cell antigen PCA‐1, and negative for the B‐cell determinant B4 and for Leu‐1, which has been postulated to distinguish a subpopulation of B cells that secrete IgM with autoantibody activity.
The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts
Authors: Hakim A. M. , Pokrupa R. P. , Villanueva J. , Diksic M. , Evans A. C. , Thompson C. J. , Meyer E. , Yamamoto Y. L. , Feindel W. H.
Published: January 2005

Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRo2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 ± 2.5 ml/100 gm/min (mean ± SEM) and was in every patient lower than that in C (33.1 ± 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 ± 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 ± 1.5). In Group I, region I showed a CMRGlc(N)/CMRo2 ratio of 0.22 ± 0.06 and a CpH of 6.83 ± 0.06. In Group 2, the same ratio in the region I was 0.58 ± 0.09 and the CpH was 7.12 ± 0.05. The CMRGlc (N)/CMRo2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRo2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed.
Multiple sclerosis disease activity correlates with gadolinium‐enhanced magnetic resonance imaging
Authors: Gonzalez‐Scarano F. , Grossman Robert I. , Galetta Steve , Atlas Scott W. , Silberberg Donald H.
Published: January 2005

Magnetic resonance imaging provides a method of visualizing multiple sclerosis plaques, but the age and activity of these plaques cannot be determined with routine magnetic resonance images. Gadolinium DTPA is a paramagnetic contrast agent that does not cross an intact blood–brain barrier. We studied 16 patients with multiple sclerosis, using magnetic resonance imaging, gadolinium‐enhanced magnetic resonance imaging, and computed tomographic scans. Gadolinium enhancement of multiple sclerosis plaques correlated with the clinical activity of the disease and corresponded anatomically with the symptoms and signs. We conclude that gadolinium enhancement of magnetic resonance images is a promising tool in the investigation of multiple sclerosis lesions and that it may provide a method for objective follow‐up in clinical trials.
Calcium channels and calcium channel antagonists
Authors: Greenberg David A.
Published: January 2005

Changes in free intracellular Ca2+ levels provide signals that allow nerve and muscle cells to respond to a host of external stimuli. A major mechanism for elevating the level of intracellular Ca2+ is the influx of extracellular Ca2+ through voltage‐dependent channels in the cell membrane. Recent research has yielded new insights into the physiological properties, molecular structure, biochemical regulation, and functional heterogeneity of voltage‐dependent Ca2+ channels. In addition, Ca2+ channel antagonist drugs have been developed that are valuable both as probes of channel structure and function and as therapeutic agents. Preliminary evidence suggests that these drugs may be useful in the treatment of diverse neurological disorders, including headache, subarachnoid hemorrhage, stroke, and epilepsy.
Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease
Authors: Fabbrini G. , Juncos J. , Mouradian M. M. , Serrati C. , Chase T. N.
Published: January 2005

The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long‐term administration was studied in 28 parkinsonian patients. The rate of levodopa clearance from the general circulation, its plasma half‐life, and apparent volume of distribution were indistinguishable between patients with the on‐off or the wearing‐off phenomenon and those with a stable response to levodopa or those who had not been previously treated with levodopa. Peripheral pharmacokinetic factors are thus unlikely to account for the development of these response fluctuations. Conversely, the efficacy half‐time of levodopa differed markedly among the four response groups studied and may provide a quantitative index of central mechanisms that favor the development of the wearing‐off and on‐off phemonena. Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half‐time. The wearing‐off phenomenon may primarily reflect the loss of buffering capacity caused by degeneration of the dopamine neurons, while the development of the on‐off phenomenon appears to require additional postsynaptic changes, possibly at the receptor level.
Rett's syndrome: Characterization of respiratory patterns and sleep
Authors: Glaze Daniel G. , Frost James D. , Zoghbi Huda Y. , Percy Alan K.
Published: January 2005

Rett's syndrome is a progressive disorder that occurs in females and is characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. Patients with Rett's syndrome have been observed to have stereotyped hand movements (hand‐washing) and to exhibit intermittent hyperventilation. To characterize more precisely the sleep and respiratory patterns associated with this disorder, polygraphic studies were made during sleep and wakefulness in 11 patients with this syndrome. These studies showed abnormal respiratory patterns during wakefulness, and abnormal sleep and electroencephalographic characteristics. The patients had decreased percentages of rapid‐eye‐movement sleep, and during wakefulness, a pattern of disorganized breathing was observed in all 11 patients and consisted of hypoxia followed by a period of increased respiratory rate and effort. The occurrence of disorganized breathing and compensatory hyperpnea during wakefulness with regular, continuous breathing during sleep is characteristic of Rett's syndrome and suggests an altered or impaired voluntary/behavioral respiratory control system.
Cerebral ptosis with contralateral arteriovenous malformation: A report of two cases
Authors: Lowenstein Daniel H. , Koch Thomas K. , Edwards Michael S.
Published: January 2005

We describe two patients with chronic unilateral ptosis and contralateral hemispheric arteriovenous malformations. Both patients were brought to our attention after a subacute or acute neurological deterioration. Analysis of prior photographs showed the ptosis progressed up to the time of presentation and significantly resolved following surgical removal of the arteriovenous malformation. The partially reversible and chronic nature of the ptosis in these two patients represents a particularly unusual form of cerebral ptosis.
Peptide‐containing nerve fibers in human cerebral arteries: Immunocytochemistry, radioimmunoassay and in vitro pharmacology
Authors: Edvinsson Lars , Ekman Rolf , Jansen Inger , Ottosson Anders , Uddman Rolf
Published: January 2005

Nerve fibers containing neuropeptide Y, vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin generelated peptide (CGRP) were seen in the adventitia or at the adventitia–media border of human cerebral arteries obtained during neurosurgical procedures Radioimmunoassay of human cerebral arteries, removed at autopsy, revealed that the levels of the four peptides did not differ among the major cerebral arteries. There was, however, a gradual decline in peptide concentrations with increasing age of the patients, as measured in the proximal part of the middle cerebral artery. Pharmacological experiments on fresh segments of cerebral (pial) arteries in vitro revealed that neuropeptide Y caused vasoconstriction per se but did not potentiate the contractile response of noradrenaline. VIP, peptide histidine methionine‐27 (PHM‐27), SP, neurokinin A (NKA), and human CGRP potently relaxed vessels precontracted by prostaglandin F2α, the relative potency being human CGRP ≥ SP ≥ VIP ≥ NKA ≥ PHM‐27. The amount of relaxation varied between 55% (SP) and 96% (human CGRP) of the prostaglandin F2α–induced contraction. The peptide effects were not antagonized by propranolol, atropine, or cimetidine, suggesting an action that does not involve adrenergic, cholinergic, or histaminergic receptors.
Neural cell adhesion molecule in normal, denervated, and myopathic human muscle
Authors: Cashman Neil R. , Covault Jonathan , Wollman Robert L. , Sanes Joshua R.
Published: January 2005

The neural cell adhesion molecule (N‐CAM) is a cell‐surface glycoprotein that may mediate some intercellular adhesive interactions in the nervous system. In adult rat muscle, N‐CAM is concentrated near neuromuscular junctions and on satellite cells, but is nearly undetectable in nonsynaptic portions of myofibers. However, N‐CAM is abundant throughout myofibers in denervated and regenerating muscles. Using affinity‐purified antibodies to N‐CAM, we were able to demonstrate a similar distribution and regulation of N‐CAM in human muscle. Myofiber N‐CAM was not detectable immunohistochemically in any of 10 normal biopsies or in 4 biopsies that were abnormal but showed no evidence of fiber denervation or regeneration. N‐CAM was present, however, at end plates, nerves, and satellite cells in normal human muscle. In contrast, myofiber N‐CAM was detected in 16 of 16 patients with histological evidence of denervation and in 10 of 10 patients who had myopathy with degenerating/regenerating myofibers. In addition, 2 of 2 histologically nondiagnostic biopsies from patients with amyotrophic lateral sclerosis contained N‐CAM–positive myofibers. Immunoblot analysis also detected N‐CAM in denervated and myopathic, but not normal, human muscle. These results suggest that N‐CAM may play a role in muscle reinnervation or regeneration and that N‐CAM immunohistochemistry may complement conventional techniques in the diagnosis of neuromuscular disease.
β‐Endorphin, ACTH, and catecholamine responses in chronic autonomic failure
Authors: Polinsky Ronald J. , Brown Robert T. , Lee Grace K. , Timmers Kim , Culman Juraj , Foldes Ondrej , Kopin Irwin J. , Recant Lillian
Published: January 2005

Plasma epinephrine (EPI), norepinephrine (NE), β‐endrophin, and corticotropin (ACTH) responses were measured during insulin‐induced hypoglycemia in normal subjects and in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). In normal subjects, there was a striking rise in EPI, NE, β‐endorphin, and ACTH following the nadir of hypoglycemia. Both β‐endorphin and ACTH responses were significantly lower than normal in patients with MSA, in contrast to normal levels in IOH patients. No correlation was observed between the degree of adrenergic insufficiency and the β‐endorphin and ACTH responses. The normal peptide responses in IOH are consistent with involvement limited to the peripheral sympathetic nervous system, whereas lesions in the central nervous system in MSA interfere with release of β‐endorphin and ACTH in response to hypoglycemia. The strong correlation between β‐endorphin and ACTH levels is consistent with their common origin. Peripheral adrenergic activity is not essential for β‐endorphin and ACTH release in humans.
Biochemical and genetic characterization of type I familial amyloidotic polyneuropathy
Authors: Nakazato Masamitsu , Sasaki Hiroyuki , Furuya Hirokazu , Sakaki Yoshiyuki , Kurihara Teruyuki , Matsukura Shigeru , Kangawa Kenji , Matsuo Hisayuki
Published: January 2005

Type I familial amyloidotic polyneuropathy is an autosomal dominant, inherited systemic amyloidosis characterized initially by dissociated sensory disturbance and autonomic dysfunction. The amyloid fibril protein seen in patients of Portuguese, Japanese, and Swedish descent in the U.S. mainly consists of a variant form of transthyretin (also called prealbumin) with the substitution of methionine for valine at position 30. Methods have been developed to detect this variant transthyretin in the serum, and to detect a base change in a mutated transthyretin gene. The biochemical and genetic abnormalities in transthyretin are completely linked to the clinical diagnosis of type I familial amylodotic polyneuropathy. These diagnostic methods may allow early diagnosis and genetic counseling to avoid transmission of this intractable disorder to the next generation.
Symptomatic atlantoaxial dislocation in Down's syndrome
Authors: Chaudhry Vinay , Sturgeon Carol , Gates A. Joanne , Myers Gary
Published: January 2005

Four patients with Down's syndrome suffered compression of the spinal cord secondary to atlantoaxial dislocation. All four developed inability to walk and quadriparesis, with signs of cervical myelopathy. It is important to recognize this potentially fatal complication of the syndrome. Immediate immobilization of the neck, followed by cervical roentgenograms, should be done in any patient with Down's syndrome who presents with neck pain, torticollis, urinary incontinence, or loss of ambulation. Surgical repair with fusion of the first and second cervical vertebrae can be carried out later.
Increased reactivity to HTLV‐I in inflammatory nervous system diseases
Authors: Lolli Francesco , Fredrikson Sten , Kam‐Hansen Slavenka , Link Hans
Published: January 2005

The presence of IgG antibodies reacting with purified and disrupted human T‐lymphotropic virus type I (HTLV‐I) was examined by an indirect enzyme‐linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain‐Barré syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV‐I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV‐I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV‐I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti‐HTLV‐I–IgG antibodies by the 24‐hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV‐I antigen–coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV‐I–related human retrovirus in the etiology of MS.
Adult‐onset spinocerebellar syndrome with idiopathic vitamin E deficiency
Authors: Yokota Takanori , Wada Yoshiaki , Furukawa Tetsuo , Tsukagoshi Hiroshi , Uchihara Toshiki , Watabiki Sadakiyo
Published: January 2005

A 62‐year‐old man and his maternal uncle had a selective vitamin E deficiency without generalized fat malabsorption. A progressive neurological disorder comprising ataxia, areflexia, and loss of proprioception developed in their sixth and seventh decades. The vitamin E deficiency is thought to be due to abnormally accelerated utilization, excretion, or degradation of the vitamin. This adult‐onset spinocerebellar syndrome is due to vitamin E deficiency not caused by malabsorption.
Platelet membrane abnormality in Alzheimer's disease
Authors: Zubenko George S. , Cohen Bruce M. , Boller Francois , Malinakova Ivana , Keefe Nanci , Chojnacki Bonnie
Published: January 2005

Fluorescence studies of membrane fluidity were conducted double‐blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid–aqueous interface regions of cell membranes was determined at 37°C by fluorescence spectroscopy using the lipid probes 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) and 1‐[4‐(trimethylamino)phenyl]‐6‐phenyl‐1,3,5‐hexatriene (TMA‐DPH), respectively. The rotation rate of TMA‐DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 ± 0.24 × 108/sec, SD) was greater than that for the normal controls (1.93 ± 0.13 × 108/sec, SD, p = 3.8 × 10−5). This difference was reflected by a reduction in the steady‐state anisotropy of DPH in labeled platelets from the demented group (0.1887 ± 0.0085, SD) when compared to the respective mean for the controls (0.2000 ± 0.0060, SD; p = 1.3 × 10−7). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with Decemberreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.
The effect of hyperosmotic blood—brain barrier disruption on blood‐to‐tissue transport in ENU‐induced gliomas
Authors: Warnke Peter C. , Blasberg Ronald G. , Groothuis Dennis R.
Published: January 2005

Hyperosmotic blood—brain barrier disruption transiently increases the rate of blood‐to‐tissue transport of water soluble compounds to normal brain and has been used in brain tumor patients to increase the delivery of chemotherapeutic drugs. This method remains controversial; debate concerns the extent to which it increases drug delivery to brain tumors. Ethylnitrosourea (ENU)‐induced gliomas in rats have the lowest rate of blood‐to‐tissue transfer of the water‐soluble compound alpha‐aminoisobutyric acid of all experimental brain tumor studied to date. To gain further understanding about the effect of hyperosomotic blood—brain barrier disruption in brain tumors, we measured the unidirectional blood‐to‐tissue transfer constant of alpha‐aminoisobutyric acid in ENU‐induced brain tumors in rats after hyperosmotic disruption. Hyperosmotic blood—brain barrier disruption with 1.6 osmolar mannitol resulted in an averaged whole‐tumor transfer constant of 0.013 ± 0.003 (standard error) mL/(g/min), compared to a transfer constant of 0.007 ± 0.002 mL/(g/min) for ENU‐induced gliomas in the contralateral undisrupted hemisphere, a difference that was not significant. In contrast, hyperosmotic blood—brain barrier disruption produced a large and significant increase in the transfer constant of alpha‐aminoisobutyric acid in tumor‐free cortex (from 0.002 ± 0.001 to 0.05 ± 0.011 mL/{g/min}) and in tumor‐free corpus callosum (from 0.001 ± 0.003 to 0.017 ± 0.005 mL/{g/min}). Hyperosmotic blood—brain barrier disruption does not appear to be an efficient method with which to increase the rate of delivery of water‐soluble drugs to brain tumors but does result in a significant increase in the delivery rate of these drugs to normal brain tissue.
Hippocampal neuron loss in temporal lobe epilepsy: Correlation with early childhood convulsions
Authors: Sagar H. J. , Oxbury J. M.
Published: January 2005

Hippocampal neuron densities in three areas (H1 zone, end folium, and dentate gyrus) were counted in each of 32 temporal lobectomy excision specimens using the technique of Mouritzen Dam. The association between severe neuronal loss in all three areas and early childhood convulsions that were prolonged and/or lateralized was highly significant. Lesser degrees of neuron loss in H1 and/or end folium were common and were not associated with early childhood convulsions, but were most often found in older patients with a particularly long history of epilepsy.
Localization of magnetic interictal discharges in temporal lobe epilepsy
Authors: Rose Douglas F. , Sato Susumu , Smith Paul D. , Porter Roger J. , Theodore William H. , Friauf Walter , Bonner Robert , Jabbari Bahman
Published: January 2005

Three young adults with intractable complex partial seizures were studies by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three‐dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth‐electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.
Genetic heterogeneity in Duchenne Dystrophy
Authors: Hyser Craig L. , Province Michael , Griggs Robert C. , Mendell Jerry R. , Fenichel Gerald M. , Brooke Michael H. , Miller J. Philip , Polakowska Renata , Doherty Richard A. , Quirk Stephen ,   CIDD Group
Published: January 2005

We evaluated 173 patients in the Clinical Investigation of Duchenne Dystrophy study to determine if patients from the same kindred were more alike clinically than patients within the study population as a whole. A high intrafamilial correlation was noted for age‐adjusted muscle strength scores. While noninherited factors could, in part, explain the results, it seems likely that genetic heterogeneity may contribute to the observed similarity within Duchenne dystrophy kindreds.
Seizures during barbiturate withdrawal: Relation to blood level
Authors: Theodore William H. , Porter Roger J. , Raubertas Richard F.
Published: January 2005

We studied 21 patients with complex partial seizures during phenobarbital (PB) or primidone withdrawal. Blood levels were measured daily, and seizure frequency was monitored by nursing staff and EEG‐video telemetry. Patients were monitored for one week of baseline and for five weeks after PB tapering was initiated (withdrawal). Most were observed for at least one week after levels were undetectable. When ranked seizure counts were averaged, there was a tendency for seizure rates to be highest as PB levels passed through the range 15 to 20 mg/l, compared with rates at higher or lower PB levels. There was little or no relation between the rate of PB withdrawal, other drug therapy, or initial PB level and the ratio of highest seizure frequency to mean seizure frequency. Patients withdrawing from PB may be most likely to experience an increase in seizure frequency when their PB blood level falls below 20 mg/l.
Basal forebrain—lesioned monkeys are severely impaired in tasks of association and recognition memory
Authors: Irle Eva , Markowitsch Hans J.
Published: January 2005

Six squirrel monkeys received ibotenic acid–induced lesions targeted to the basal nucleus of Meynert (BNM). Postoperatively, the monkeys were trained in a broad spectrum of learning tasks and compared to normal and sham‐operated controls. The lesioned monkeys showed severe and enduring learning and memory deficits in a visual reversal task, several concurrent object discriminations, a delayed nonmatch‐to‐sample task, and, most outstanding, an angle threshold discrimination. Although in some of the monkeys the BNM was lesioned only partly with some surrounding tissue affected as well, the lesion of the BNM appears to be crucial in the large and apparently irreversible learning deficits of the monkeys. However, final proof for this suggestion is still needed.
Prospective nerve conduction studies in cisplatin therapy
Authors: Riggs Jack E. , Ashraf Mohammed , Snyder Robert D. , Gutmann Ludwig
Published: January 2005

We studied nerve conduction prospectively in 38 women receiving cisplatin for gynecological malignancies. Decreased sensory nerve action potential amplitudes and prolonged sensory latencies were the only significant changes identified. This prospective electrophysiological study validates the clinical observation of frequent sensory symptoms and occasional sensory neuropathies associated with cisplatin therapy.
Cortical somatostatin, neuropeptide Y, and NADPH diaphorase neurons: Normal anatomy and alterations in alzheimer's disease
Authors: Kowall Neil W. , Beal M. Flint
Published: January 2005

Somatostatin and neuropeptide Y are two neuropeptides that are of particular in Alzheimer's disease because they are reported to be depleted in cerebral cortex. In the present study we examined somatostatin, neuropeptide Y, and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase neurons in nine cortical regions in both normal and Alzheimer's disease brains. These three neurochemical markers show a high degree of co‐localization (> 90%) in nonpyramidal neurons that are primarily distributed in cortical layers II‐III, V‐VI, and, most prominently, in infracortical white matter. The highest cell density was in temporal and parietal association cortex. The major morphological abnormality in Alzheimer's disease brains was a marked pruning and distortion of fiber plexuses with an apparent reduction in fiber density. In contrast, perikaryal density was preserved except for a reduction in parietal association cortex. Approximately 10 to 15% of senile plaques in the inferior temporal gyrus contained abnormal neurites. Additional abnormal collections of neurites without plaque cores were frequently found in layers II‐III and V‐VI. Neuropeptide Y and somatostatin were co‐localized in abnormal neurites, suggesting an origin from local intrinsic neurons in which the two peptides are co‐localized. Double immunofluorescence staining for both tau protein, a major antigenic component of paired helical filaments, and either somatostatin or neuropeptide Y showed that these neurons do not contain tau‐immunoreactive neurofibrillary tangles. The morphological correlate of reduced somatostatin and neuropeptide Y content in Alzheimer's disease brain therefore appears to be a distortion and reduction in fiber plexuses. In addition, it is apparent that these neurons can develop widespread morphological abnormalities in the absence of neurofibrillary tangle formation.
X‐Linked myopathy with excessive autophagy: A new hereditary muscle disease
Authors: Kalimo Hannu , Savontaus Marja‐Liisa , Lang Heikki , Paljärvi Leo , Sonninen Vesa , Dean Peter B. , Katevuo Kalevi , Salminen Antero
Published: January 2005

We report on 3 brothers with a myopathy that also affected their maternal grandfather and great‐uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X‐linked myopathy with excessive autophagy.
Striatal calcium channel antagonist receptors in huntington's disease and parkinson's disease
Authors: Watson Daniel L. , Carpenter Celia L. , Marks Shelley S. , Greenberg David A.
Published: January 2005

The density of calcium channel antagonist receptors labeled by (+)‐[3H]PN 200‐110 was reduced by 75% in striata from patients with Huntington's disease, but unchanged in patients with Parkinson's disease, compared with control subjects. These receptors are therefore likely to be localized to neurons with cell bodies in striatum, rather than nigrostriatal nerve terminals or glia, and their loss may contribute to the pathophysiology of basal ganglia disorders.
Plasmapheresis and guillain‐barré syndrome: Analysis of prognostic factors and the effect of plasmapheresis
Authors: McKhann G. M. , Griffin J. W. , Cornblath D. R. , Mellits E. D. , Fisher R. S. , Quaskey S. A. ,   The Guillain‐Barré Syndrome Study Group
Published: January 2005

The time course of recovery in the Guillain‐Barré syndrome is known to vary widely, but factors associated with differences have not been previously defined. In this study we used multivariate analysis to identify such factors and to determine whether the presence or absence of specific factors would influence treatment decisions, particularly the use of plasmapheresis. Data from 245 patients randomized into conventional and plasmapheresis arms were used to assess the time to walk independently (Grade 2), the time to improve one grade, and the percentage improved at 4 weeks. Individually, many factors were associated with outcome. In the multivariate analysis, four factors correlate with poorer outcomes: mean amplitude of compound muscle action potential on stimulating distally of 20% of normal or less, older age, time from onset of disease of 7 days or less, and need for ventilatory support. The most powerful predictor of outcome was the abnormal mean amplitude of compound muscle action potential on stimulating distally. Plasmapheresis, the only variable the physician can influence, has a beneficial effect over and above any or all of these factors. The plasmapheresis patients on continuous flow machines had better outcomes than those on intermittent flow machines. From these data, tables of expected outcome probabilities have been developed.
Aphasia in senile dementia of the alzheimer type
Authors: Faber‐Langendoen Kathy , Morris John C. , Knesevich John W. , LaBarge Emily , Miller J. Philip , Berg Leonard
Published: January 2005

We assessed language function, using a brief clinical Aphasia Battery and psychometric measures, in 150 subjects with senile dementia of the Alzheimer type (SDAT) and 83 elderly controls. Aphasia occurred only in demented subjects, and its prevalence increased with severity of dementia. Aphasia in mildly demented subjects was associated with both an earlier age of onset and more rapid progression of SDAT than in similarly demented nonaphasics. Language dysfunction in SDAT subjects was characterized by early decline in measures of comprehension and written expression, whereas other components, including oral naming, were less profoundly affected. Performance on the verbal psychometric measures, the Sentence Repetition and the Token tests, correlated strongly with Aphasia Battery scores and declined only minimally in nonaphasics, despite increasing dementia. We conclude that aphasia is a common feature of SDAT subjects and identifies a subgroup with more rapid progression of dementia. Furthermore, it represents language‐specific dysfunction beyond the global cognitive impairment of SDAT.
The safety and angiographic efficacy of tissue plasminogen activator in a cerebral embolization model
Authors: Phillips David A. , Fisher Marc , Smith Thomas W. , Davis Michael A.
Published: January 2005

Thrombolysis with tissue plasminogen activator (tPA) has been used to treat myocardial infarction and pulmonary embolism in humans. This plasminogen activator may also be useful in treating certain strokes. We infused tPA or saline in rabbits 15 minutes after selective internal carotid artery embolization with 18‐hour aged autologous clot. By serial angiography, the tPA‐treated group demonstrated rapid angiographic reperfusion of the occluded vascular territory in 7 of 8 animals, whereas none of 6 saline controls did. None of the animals in either group developed macroscopic cerebral hemorrhage. Both groups showed cerebral infarction, predominantly in the territory of the occluded vessel; the extent of infarction did not differ between tPA‐treated animals and controls. Early tPA therapy can allow reperfusion of occluded cerebral arteries safely and effectively in a rabbit cerebral embolization model.
Sleep apnea in olivopontocerebellar degeneration: Treatment with trazodone
Authors: Salazar‐Grueso Edgar F. , Rosenberg Richard S. , Roos Raymond P.
Published: January 2005

A 37‐year‐old man with a 19‐year history of progressive autosomal‐dominant olivopontocerebellar degeneration developed excessive daytime sleepiness and paroxysmal episodes that clinically resembled an ictal or postictal state. Polysomnography showed sleep apnea. Long‐term therapy with trazodone resulted in resolution of the paroxysmal episodes, disappearance of daytime sleepiness, and gradual improvement of sleep architecture over several months.