bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection
Authors: Brew Bruce J. , Bhalla Ravi B. , Paul Morris , Gallardo H. , McArthur Justin C. , Schwartz Morton K. , Price Richard W.
Published: January 2005

We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood‐brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease‐specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.
Aggravation of myasthenia gravis by erythromycin
Authors: May Eugene F. , Calvert Preston C.
Published: January 2005

Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction.
Familial Creutzfeldt‐Jakob disease without periodic EEG activity
Authors: Tietjen Gretchen E. , Drury Ivo
Published: January 2005

Four members of a kindred with Creutzfeldt‐Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt‐Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt‐Jakob disease, as it is in other slow transmissible encephalopathies.
Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti‐neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration
Authors: Sakai Koichiro , Mitchell Dennis J. , Tsukamoto Tetsuro , Steinman Lawrence
Published: January 2005

We isolated a complementary DNA clone encoding a 52‐kd protein recognized by an antineuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti‐neuronal cell antibody from the patient, and its molecular weight was identical to that of antigenic proteins in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydrophilic residues, the calculated relative molecular mass was 51,238, and the predicted value of the isoelectric point was 4.99. This complementary DNA sequence and the deduced protein sequence have not been reported previously, and the sequences showed no homologies with the complimentary DNA or the amino acid sequences in the GenBank, EMBL, or NBRF databases, including the complementary DNA for a 34‐kd cerebellar protein (CDR34) that is recognized by an anti‐Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue, the intestine.
Normal proprioceptive trigeminal afferents in patients with Sjögren's syndrome and sensory neuronopathy
Authors: Valls‐Sole Josep , Graus Francesc , Font Josep , Pou Adolf , Tolosa Eduard S.
Published: January 2005

A pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described in patients with Sjögren's syndrome. Conventional electromyographic (EMG) studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion. Noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei, respectively, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigeminal reflexes in 5 patients with Sjögren's syndrome and pure sensory neuropathy, in 10 patients with sensory‐motor neuropathies of other causes, and in 10 healthy subjects. Our results show that patients with Sjögren's syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal, cutaneous‐induced masseter silent period had normal jaw jerks, whereas patients with sensory‐motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks. These findings suggest that the lesion in pure sensory neuropathy involves damage to the neurons of the gasserian ganglia and not to the trigeminal axons, since an axonal lesion would be expected to involve the large axons from muscle spindle receptors.
Striatal function in normal aging: Implications for Parkinson's disease
Authors: Sawle G. V. , Colebatch J. G. , Shah A. , Brooks D. J. , Marsden C. D. , Frackowiak R. S. J.
Published: January 2005

Central to several current theories of the etiology of Parkinson's disease is the premise that the nigrostriatal dopaminergic system degenerates with normal aging. Much of the evidence for this assertion has come from postmortem neurochemical studies. We have used L‐6‐[18F]fluoro‐Dopa and positron emission tomography in 26 healthy volunteers (age range, 27–76 years) to examine striatal and frontal cortical tracer uptake. Data have been analyzed by using a graphical approach to calculate an influx constant (Ki) for L‐6‐[18F]fluoro‐Dopa uptake into the caudate, putamen, and medial frontal cortex of each subject. In the population studied, there was no decline in Ki with age for any of these structures. A series of physiological measurements made on the older subjects also showed few significant changes with age. The positron emission tomographic findings demonstrate preservation of nigrostriatal dopaminergic function in normal aging. The pathological process causing Parkinson's disease may operate closer to the time of presentation than has been suggested.
Effects of treatment on long‐term survivors with malignant astrocytomas
Authors: Imperato Joseph P. , Paleologos Nina A. , Vick Nicholas A.
Published: January 2005

We reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long‐term consequences of radiation therapy and chemotherapy. We defined long‐term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100% longer than median survival of historical controls, for example, 2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma. There were 9 (5.6%) long‐term survivors. Three (30%) became demented and died without evidence of tumor recurrence. One, after survival of 10 years, died of tumor recurrence. Of the remaining survivors, 2 (22%) have significantly impaired short‐term memory function and other neurological deficits such as gait apraxia. Three (30%) can function independently. It is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome. Our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas, such as low‐grade astrocytomas and oligodendrogliomas.
Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis
Authors: van der Kamp W. , de Noordhout A. Maertens , Thompson P. D. , Rothwell J. C. , Day B. L. , Marsden C. D.
Published: January 2005

Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger. The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination. The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal. There were strong correlations between all these measures. Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation. That is, the longer the central motor conduction time, the weaker the force. Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways. The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se. These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength. There also was some correlation of central motor conduction time, twitch force, and voluntary phasic force with the performance of tests of manual dexterity. Since the voluntary phasic strength and twitch force to cortical stimulation were similarly weakened, the findings would also be consistent with the cortical stimulus and voluntary contraction using the same descending motor tracts.
Developmental regulation of human truncated nerve growth factor receptor
Authors: DiStefano Peter S. , Clagett‐Dame Margaret , Chelsea Diane M. , Loy Rebekah
Published: January 2005

Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF‐Rt) were used in a two‐site radiometric immunosorbent assay to monitor levels of NGF‐Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two‐site radiometric immunosorbent assay, NGF‐Rt levels were found to be highest in urine from 1‐month old subjects. By 2.5 months, NGF‐Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF‐Rt levels were relatively constant at 5% of 1‐month values. No evidence for diurnal variation of adult NGF‐Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF‐Rt values compared with age matched normals. Affinity labeling of NGF‐Rt with 125I‐NGF followed by immunoprecipitation with ME20.4‐IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF‐Rt were observed on gel autoradiograms with development, indicating that the two‐site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF‐Rt. NGF‐Rt in urines from 1‐month‐old and 36‐year‐old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF‐Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system. The results obtained in this study establish the basis for studying NGF‐Rt regulation during the course of abnormal development, regeneration, and neurodegeneration.
Localization of 3H‐Dihydroergotamine‐binding sites in the cat central nervous system: Relevance to migraine
Authors: Goadsby Peter J. , Gundlach Andrew L.
Published: January 2005

Dihydroergotamine (DHE) is the treatment of choice in aborting the acute attack of migraine. Although its efficacy has been known for 40 years, its mechanism of action is still disputed. Data regarding the site of action of dihydroergotamine may provide an insight into its mechanism of action and thus identify a locus of potentially abnormal pathophysiology in migraine. By using in vitro and ex vivo autoradiographic techniques, the localization of specific binding sites for 3H‐dihydroergotamine in the cat brain has been examined. Binding was seen in the dorsal horn of the cervical spinal cord, in the medulla, associated with the nucleus of the tractus solitarius, area postrema, and descending spinal trigeminal nucleus, and in the mesencephalon and the cerebral cortex. The highest density of binding sites was found in the dorsal and medial raphe nuclei of the midbrain. Furthermore, these same brain regions were also labeled after intravenous administration of 3H‐dihydroergotamine. It is important that the brain areas specifically labeled are key nuclei involved in cranial pain transmission, suggesting that dihydroergotamine may act at these central sites in migraine.
Quinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy
Authors: Kish Stephen J. , Du Fu , Parks Deborah A. , Robitaille Yves , Ball Melvyn J. , Schut Lawrence , Hornykiewicz Oleh , Schwarcz Robert
Published: January 2005

We measured the activities of the enzymes responsible for the metabolism of the excitotoxin quinolinic acid, 3‐hydroxyanthranilate oxygenase and quinolinic acid phosphoribosyltransferase, in autopsied brain of 11 patients with olivopontocerebellar atrophy. In cerebellar cortex, severe Purkinje cell loss was evident but with relative preservation of granule cells. As compared with the control subjects (n = 14), mean activity of 3‐hydroxyanthranilate oxygenase was normal in cerebellar cortex from the patients with olivopontocerebellar atrophy, whereas quinolinic acid phosphoribosyltransferase activity was markedly increased (+ 92%, p < 0.02). No significant changes in enzyme activities were found in samples from occipital cortex. Increased quinolinic acid phosphoribosyltransferase activity may represent a mechanism, in the degenerating cerebellum, to protect quinolinic acid–sensitive granule cells in patients with olivopontocerebellar atrophy.
Intraspinal transplants
Authors: Tessler Alan
Published: January 2005

Transplants of embryonic central nervous system tissue have long been used to study axon growth during development and regeneration, and more recently to promote recovery in models of human diseases. Transplants of embryonic substantia nigra correct some of the deficits found in experimental Parkinson's disease, for example, by mechanisms that are thought to include release of neurotransmitter and reinnervation of host targets, as well as by stimulating growth of host axons. Similar mechanisms appear to allow intraspinal transplants of embryonic brainstem to reverse locomotor and autonomic deficits due to experimental spinal cord injuries. Embryonic spinal cord transplants offer an additional strategy for correcting the deficits of spinal cord injury because, by replacing damaged populations of neurons, they may mediate the restoration of connections between host neurons. We have found that spinal cord transplants permit regrowth of adult host axons resulting in reconstitution of synaptic complexes within the transplat that in many respects resemble normal synapses. Transplants of fetal spinal cord may also contribute to behavioral recovery by rescuing axotomized host neurons that otherwise would have died. Electrophysiological and behavioral investigations of functional recovery after intraspinal transplantation are preliminary, and the role of transplants in the treatment of human spinal cord injury is uncertain. Transplants are contributing to our understanding of the mechanisms of recovery, however, and are likely to play a role in the development of rational treatments.
Genetic mapping of “Lubag” (X‐linked dystonia‐parkinsonism) in a filipino kindred to the pericentromeric region of the X chromosome
Authors: Wilhelmsen Kirk C. , Weeks Daniel E. , Nygaard Torbjoern G. , Moskowitz Carol B. , Rosales Raymond L. , Dela Paz Daniel C. , Sobrevega Eufemio E. , Fahn Stanley , Gilliam T. Conrad
Published: January 2005

“Lubag” is an X‐linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, Principally from the island of Panay. We have established linkage between the disease phenotype “lubag” and DNA markers which span the Xp11.22‐Xq21.3 region by using a large Filipino family with 8 affected men in three generations. These DNA markers define an interval of about 20 centimorgans in the pericentromeric region of the X chromosome as the most likely site of the disease locus XDPD (X‐linked dystonia‐parkinsonism). XDPD has a maximum multipoint log likelihood ratio score (Zmax) of about 4.6 over the interval from Xq12 to Xq21.31 (DXS159‐DXYS1X). The co‐occurrence of dystonia and parkinsonism in lubag and in other known disorders suggests there may be a common pathogenetic mechanism. Identification of the genetic defect in this family may provide an important clue toward understanding the pathogenesis and pathophysiology of both dystonia and parkinsonism.
Human microglial cells: Characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV‐1 infection
Authors: Peudenier Sylviane , Hery Christiane , Montagnier Luc , Tardieu Marc
Published: January 2005

Neuropathological studies have shown that human immunodeficiency virus type 1‐infected cells within the brain express several markers characteristic of macrophages and could either be microglial cells, or monocytes invading the CNS, or both. To better define the target cells of human immunodeficiency virus type 1 within the brain, we have studied human microglial cells, both in vivo and in vitro, and compared them to monocytes for their antigenic markers and their susceptibility to human immunodeficiency virus type 1 infection. Brain‐derived macrophages were isolated from primary cortical and spinal cord cultures obtained from 8 to 12‐week‐old human embryos. The isolated cells presented esterase activity, phagocyted zymosan particles, expressed several (Fc receptors, and CD68/Ki‐M7 and CD11b/CR3 receptors) of the macrophagic antigenic markers, and appeared to be resident microglial cells from human embryonic brain. Conversely, brain‐derived macrophages did not express antigens CD4, CD14, or CD68/Ki‐M6, which are easily detected on freshly isolated monocytes. Using these antigenic differences between isolated microglial cells and monocytes, we have observed that two populations of macrophages could be individualized. In the normal adult brain, microglial cells were numerous in both the gray and the white matter. The infrequent cells sharing antigens with monocytes were found almost exclusively around vessels. In 8 to 12‐week‐old human embryos, microglial cells were found in both the parenchyma and the germinative layer. Cells sharing antigens with monocytes were only found at the top of and inside the germinative layer. In brain tissue from patients with human immunodeficiency virus type 1 encephalitis, cells sharing antigens with monocytes are abundant not only around the vessels but also in the parenchyma. In double‐labeling experiments, human immunodeficiency virus type 1‐infected cells showed monocyte antigens. Finally, microglial cells also differ from monocytes in their in vitro susceptibility to human immunodeficiency virus type 1 infection; after stimulation by r‐TNFα or GmCSF, monocytes but not microglial cells can replicate human immunodeficiency virus type 1. This in vitro difference in human immunodeficiency virus type 1 susceptibility between monocytes and microglial cells together with the presence of monocytic antigens within the brain tissue of human immunodeficiency virus type 1‐infected patients suggest that human immunodeficiency virus type 1‐infected cells within the brain are either monocytes that have crossed the blood‐brain barrier and spread through the tissue or perivascular microglial cells that, after phagocyting infected blood lymphocytes, subsequently contain viral antigen and migrate to brain tissue.
Glutamate‐, glutaminase‐, and taurine‐immunoreactive neurons develop neurofibrillary tangles in Alzheimer's disease
Authors: Kowall Neil W. , Beal M. Flint
Published: January 2005

Although formation of neurofibrillary tangles is a major pathological feature of Alzheimer's disease (AD), the neurotransmitter content of neurofibrillary tangle‐bearing neurons has not been well characterized. We studied the hippocampus of 6 patients with pathologically verified AD and 6 control subjects using a monoclonal antibody to glutamyl‐glutamate and polyclonal antisera against glutaminase and taurine. In normal hippocampus, gluamate and glutaminase stained pyramidal neurons in the cornu ammonis (CA) fields and the subiculum, as well as the dentate granule cells. Fiber staining was better seen with glutamate antisera, which in AD specimens showed reduced numbers of glutamate‐immunoreactive fibers in the molecular layer of the dentate gyrus. In AD specimens, glutamate‐ and glutaminase‐immunoreactive pyramidal neurons in the hippocampal CA fields were decreased in number and remaining neurons showed irregular shortened and disorganized dendritic fields. Taurine immunoreactivity was localized to a subset of hippocampal pyramidal neurons, which showed similar degenerative changes in AD specimens. Glutamate‐, glutaminase‐, and taurine‐stained neurons were found to contain neurofibrillary tangles using either double immunofluorescence with tau antisera, double immunoperoxidase stains, or silver and thioflavine S counterstains. These studies show that two distinct neurochemically defined populations of pyramidal neurons in allocortex frequently show degenerative changes and develop neurofibrillary tangles in AD.
Increased HTLV‐I proviral DNA in HTLV‐I–associated myelopathy: A quantitative polymerase chain reaction study
Authors: Kira Jun‐ichi , Koyanagi Yoshio , Yamada Takeshi , Itoyama Yasuto , Goto Ikuo , Yamamoto Naoki , Sasaki Hiroyuki , Sakaki Yoshiyuki
Published: January 2005

Using the polymerase chain reaction, we quantitated the amount of human T‐lymphotropic virus type I (HTLV‐I) proviral DNA in peripheral blood mononuclear cells from 18 patients with HTLV‐I–associated myelopathy/tropical spastic paraparesis; 17 HTLV‐I carriers without HTLV‐I–associated myelopathy/tropical spastic paraparesis, with or without other autoimmune or inflammatory diseases; and 19 seronegative control subjects. The HTLV‐I proviral DNA was 10‐ to 100‐fold higher in the patients and in the HTLV‐I carriers without HAM/TSP who had autoimmune or inflammatory diseases than in the carriers without autoimmune or inflammatory diseases. The patients who had had onset of myelopathy at a younger age (15 to 39 years) had an extremely high level of HTLV‐I proviral DNA in the early phase, as compared with findings in those with a late onset of myelopathy (at 44 to 61 years). The large increase in HTLV‐I proviral DNA in peripheral blood mononuclear cells is presumably closely related to the development of autoimmune or inflammatory processes in HTLV‐I carriers, including HTLV‐I–associated myelopathy/tropical spastic paraparesis.
Peripheral neuropathy after chronic endoneurial ischemia
Authors: Sladky John T. , Tschoepe Raymond L. , Greenberg Joel H. , Brown Mark J.
Published: January 2005

We have developed a method for producing chronic regional nerve ischemia in rats by creating proximal limb arteriovenous shunts. This procedure results in a 50 to 75% reduction in endoneurial blood flow within the distal sciatic nerve as measured by the iodoantipyrine method. Nerve conduction velocities in sciatic nerves ipsilateral to the shunt fell by 25 to 30% within 2 weeks after creation of the shunt and did not recover for up to 10 months after the procedure. Morphological studies of the ischemic nerves showed structural abnormalities at nodes of Ranvier and mild axonal atrophy. Neither segmental demyelination nor axonal degeneration were evident. These results indicate that reduced endoneurial blood flow, insufficient to cause infarction, may result in measureable functional and morphological abnormalities in peripheral nerves.
Calcium channel autoantibodies in the lambert‐eaton myasthenic syndrome
Authors: Leysm Katherine , Lang Bethan , Johnston Irene , Newsom‐Davis John
Published: January 2005

We have tested 36 patients with the Lambert‐Eaton myasthenic syndrome for serum antibodies to voltage‐gated calcium channels by using an immunoprecipitation assay with [125I] ω‐conotoxin–labeled voltage‐gated calcium channels extracted from a human neuroblastoma cell line, SKN‐SH. Forty‐four percent of these patients had significant levels of antibody (30–1,466 pM) compared with healthy control individuals (< 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage‐gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti–voltage‐gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30–82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert‐Eaton myasthenic syndrome.
Magnetic resonance imaging of Creutzfeldt‐Jacob disease
Authors: Milton Walter J. , Atlas Scott W. , Lavi Ehud , Mollman Joan E.
Published: January 2005

We report a biopsy‐diagnosed patient with Creutzfeldt‐Jacob disease showing on magnetic resonance images bilateral increased signal intensity in the basal ganglia on long repetition time images. Creutzfeldt‐Jacob disease (CJD) is a degenerative process of the brain, induced by a novel infectious agent, and is usually characterized by a rapidly progressive dementia. We report a biopsydiagnosed patient with CJD with a distinctive magnetic resonance (MR) apperance.
Selective impairment of smooth‐pursuit eye movements due to an ischemic lesion of the basal pons
Authors: Thier Peter , Bachor Alexander , Faiss Jürgen , Dichgans Johannes , Koenig Eberhard
Published: January 2005

Voluntary and reflex‐like eye movements were measured in a patient with an ischemic lesion of the right basal pons. Ipsilateral smooth‐pursuit eye movements were predominantly impaired and interrupted by saccades. This profound smooth‐pursuit deficit contrasted with only minor abnormalities of visually guided saccades and the vestibulo‐ocular reflex. A selective disturbance of smooth‐pursuit eye movements due to a lesion of the basal pons in this patient concurs with recent work in monkeys suggesting that smooth‐pursuit eye movements are mediated by a parietooccipito‐ponto‐cerebellar pathway.
Coculture with autologous myotubes of cytotoxic T cells isolated from muscle in inflammatory myopathies
Authors: Hohlfeld Reinhard , Engel Andrew G.
Published: January 2005

T‐cell lines were expanded from muscle of 10 patients with polymyositis, 5 with inclusion body myositis, 5 with dermatomyositis, and 5 with other muscle diseases. All cell lines uniformly expressed T‐cell antigens, but not natural killer cell or B‐cell antigens. The proportion of helper (CD4+) and cytotoxic (CD8+) T cells in the expanded lines was variable and showed no correlation with the diagnosis. Sixteen cell lines (6 polymyositis, 4 inclusion body myositis, 5 dermatomyositis, 1 other muscle disease) consisted predominantly of CD8+ T cells. None of these lines displayed natural killer‐like cytotoxicity but all were capable of lectin‐dependent cytotoxicity. Three of 6 polymyositis, 1 of 4 inclusion body myositis, and 1 of 5 dermatomyositis lines showed low but statistically significant cytotoxicity against autologous myotubes (6 to 27% specific 51Cr release; effector‐target ratio, 20:1). The results demonstrate that functionally competent cytotoxic T cells can be expanded from muscle affected by inflammatory myopathies and are consistent with the hypothesis that some cytotoxic T cells recognize an autoantigen on myotubes. Further studies of this experimental system may define the molecular mechanism of T cell‐mediated muscle fiber injury and may help to identify the relevant antigens.
Lhermitte‐duclos disease and cowden disease: A single phakomatosis
Authors: Padberg George W. , Schot Johannes D. L. , Vielvoye G. Jan , Bots Gerard Th. A. M. , De Beer Frits C.
Published: January 2005

Two unrelated patients with macrocephaly, seizures, and mild cerebellar signs had a dysplastic gangliocytoma of the cerebellum (Lhermitte‐Duclos disease). Both also had autosomal dominant Cowden disease as evidenced by facial, oral, and acral papules. In the two families, 9 sibs demonstrated the mucocutaneous lesions, thyroid disease, breast tumors, and ovarian tumors compatible with the diagnosis of Cowden disease. Some of the sibs also showed various degrees of neurological signs such as macrocephaly, mental retardation, seizures, tremor, and dysdiadochokinesia. Magnetic resonance imaging scans of sibs of one family demonstrated megalencephaly and other mild abnormalities. The occurrence of these two rare disorders in single patients is more than a coincidence, and the clinical findings in the combined condition establishes it as a new phakomatosis.
The role of prolactin in autoimmune demyelination: Suppression of experimental allergic encephalomyelitis by bromocriptine
Authors: Riskind Peter N. , Massacesi Luca , Doolittle Teresa H. , Hauser Stephen L.
Published: January 2005

Several lines of evidence suggest that the anterior pituitary hormone prolactin has a stimulatory role on immune function and that pharmacological suppression of prolactin secretion with the dopamine‐agonist bromocriptine suppresses both humoral and cellular immunity. Here, we describe the effects of prolactin‐suppression on the course of experimental allergic encephalomyelitis in female Lewis rats. Initiation of continuous bromocriptine treatment before immunization reduced both the severity and incidence of clinical signs of acute experimental allergic encephalomyelitis. Experimental allergic encephalomyelitis–immunized rats experienced a threefold rise in basal prolactin levels on day 4 after immunization and maintained elevated prolactin levels on day 10, before the onset of neurological signs of experimental allergic encephalomyelitis. Bromocriptine treatment reduced prolactin levels to those of shamimmunized rats. In vivo bromocriptine pretreatment inhibited splenic lymphocyte proliferative responses in vitro to the immunizing antigen and to concanavalin A. Moreover, bromocriptine therapy was protective when initiated 1 week after the initial immunization and was also effective in suppression of late disease. These results indicate that (1) prolactin levels are elevated after immunization and before the onset of experimental allergic encephalomyelitis, (2) bromocriptine inhibits both prolactin secretion and the severity of acute experimental allergic encephalomyelitis, and (3) inhibition is also present when treatment is begun after sensitization, suggesting an effect of prolaction on the effector limb of the immune response during experimental allergic encephalomyelitis.
Mitochondrial dysfunction in multiple symmetrical lipomatosis
Authors: Berkovic Samuel F. , Andermann Frederick , Shoubridge Eric A. , Carpenter Stirling , Robitaille Yvon , Andermann Eva , Melmed Calvin , Karpati George
Published: January 2005

Multiple symmetrical lipomatosis is a striking clinical finding associated with a variety of peripheral and central nervous system abnormalities. We describe 4 unrelated patients with evidence of mitochondrial dysfunction in skeletal muscle. Multiple symmetrical lipomatosis is an additional, albeit unusual, manifestation of the expanding clinical spectrum of mitochondrial diseases.
Fatal varicella‐zoster virus meningoradiculitis without skin involvement
Authors: Dueland Aud N. , Devlin Mary , Martin John R. , Mahalingam Ravi , Cohrs Randall , Manz Herbert , Trombley Irene , Gilden Donald
Published: January 2005

A 77‐year‐old man with T‐cell lymphoma developed an acute fatal meningoradiculitis of cranial nerve roots and cauda equina, pathologically and virologically confirmed to be caused by varicella‐zoster virus. This is the first report of fatal varicella‐zoster virus‐induced neurological disease in the absence of skin lesions. Varicellazoster virus should be included in the differential diagnosis of acute radiculoneuropathy in the immunocompromised patient, particularly because antiviral treatment for varicella‐zoster virus exists.
Cerebrovascular abnormalities in pediatric stroke: Assessment using parenchymal and angiographic magnetic resonance imaging
Authors: Wiznitzer Max , Masaryk Thomas J.
Published: January 2005

Three‐dimensional (volume) magnetic resonance angiography is a noninvasive technique the images the intracranial and cervical arterial vasculature without contrast agents. Twenty‐four children with strokes had combined parenchymal magnetic resonance imaging and magnetic resonance angiography 1 day to 4 years after acute presentation. Eight had had prior intra‐arterial angiography. Eighteen magnetic resonance angiographic studies showed arterial stenosis or occlusion in the vascular distribution of magnetic resonance image‐defined brain infarction and, in 7 children, in the same location as previously defined abnormalities on intra‐arterial angiography. One child had a normal intra‐arterial angiogram and magnetic resonance angiogram. The other 5 children with normal magnetic resonance angiographic studies included 3 with presumed embolic disease, 1 with meningitis, and 1 with Crohn's disease‐related vasculitis. Collateral flow patterns could be determined in 4 children. Artifact presenting as filling defects in vessels was present in 10 studies, but did not interfere with interpretation of 8 studies. Combined magnetic resonance imaging/magnetic resonance angiography provides a screening technique to evaluate noninvasively brain parenchyma and vasculature in children with suspected large‐vessel abnormalities, allowing selection for intra‐arterial angiography and vasculature in children with suspected large‐vessel abnormalities, allowing selection for intra‐arterial angiography and serial monitoring of vascular abnormalities over time and during therapeutic intervention.
The acetylcholine‐induced flare response in evaluation of small fiber dysfunction
Authors: Benarroch Eduardo E. , Low Phillip A.
Published: January 2005

We inotophoresed acetylcholine on the dorsum of the foot and simultaneously measured flare and sweat responses using laser Doppler and sudorometric techniques, respectively. We compared these responses with those induced by histamine. Both acetylcholine and histamine produced dosedependent flare, but only acetylcholine produced sweat responses. Responses to acetylcholine and histamine were blocked by hexamethonium chloride and pyrilamine maleate, respectively (p < 0.01). We compared flare and sweat responses in 26 control subjects, 21 asymptomatic diabetic patients and 41 patients (17 diabetic, 24 nondiabetic) with pain symptoms suggestive of small fiber neuropathy and normal sensation (n = 15) or mild to moderate (n = 19) or severe (n = 7) sensory loss. No patient had trophic foot lesions. Basal skin blood flow and maximal flare responses were not significantly different among the various subgroups (Control subjects, 49 ± 7.4; asymptomatic diabetic patients, 29 ± 4; patients with small fiber neuropathy and normal sensation, 34 ± 6; with neuropathy and mild to moderate sensory loss, 29 ± 4.8; and with neuropathy and severe sensory loss, 35 ± 5 ml/100 gm, for flare response, respectively). Flare responses lower than the lowest found in control subjects occurred in 5 of 21 asymptomatic diabetic patients, 4 of 15 patients with small fiber neuropathy and normal sensation, 5 of 19 with neuropathy and mild to moderate sensory loss, and 1 of 7 with neuropathy and severe sensory loss. Abnormal (persistent or decreased) sweat responses occurred in 10 of 21 asymptomatic diabetic patients, 12 of 15 patients with small fiber neuropathy and normal sensation, 13 of 19 with neuropathy and mild to moderate sensory loss, and 7 of 7 with neuropathy and severe sensory loss. Acetylcholine and histamine stimulate the afferent branch of the flare axon reflex by nicotinic and H1 receptors, respectively. Concurrent measurement of flare and sweat responses, but not the flare alone, may identify patients with small fiber neuropathy, in the absence of trophic foot lesions.
Quantification of mu and non–mu opiate receptors in temporal lobe epilepsy using positron emission tomography
Authors: Mayberg Helen S. , Sadzot Bernard , Meltzer Carolyn Cidis , Fisher Robert S. , Lesser Ronald P. , Dannals Robert F. , Lever John R. , Wilson Alan A. , Ravert Hayden T. , Wagner Henry N. , Bryan R. Nick , Cromwell Christina C. , Frost J. James
Published: January 2005

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high‐affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C‐carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C‐carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C‐diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C‐carfentanil and 11C‐diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non–mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F‐2‐fluoro‐2‐deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.
Evaluation of a competitive NMDA antagonist (D‐CPPene) in feline focal cerebral ischemia
Authors: Chen M. , Bullock R. , Graham D. I. , Frey P. , Lowe D. , McCulloch J.
Published: January 2005

The effects of a competitive, N‐methyl‐D‐aspartate (NMDA) receptor antagonist, D(‐)E‐4‐(3‐phosphonoprop‐2‐enyl)‐piperazine‐2‐carboxylic acid (D‐CPPene), on the volume of ischemic brain damage was assessed by quantitative histological study in 35 chloralose‐anesthetized cats. Focal cerebral ischemia was produced by permanent occulsion of one middle cerebral artery and the animals were killed by transcardiac perfusion fixation 6 hours later. Pretreatment with D‐CPPene (1.5, 4.5, or 15 mg/kg, administered intravenously 15 minutes prior to occlusion, with subsequent drug infusions to maintain a plateau in the plasma drug concentrations) effected dose‐dependent reductions in the volume of ischemic brain damage. At the highest dose studied (15 mg/kg, plus an infusion of 170 m̈g/kg/min), D‐CPPene reduced the volume of ischemic damage in the cerebral cortex by more than 75% compared to vehicle‐treated control animals. The plasma concentration of D‐CPPene, which is associated with a half maximal reduction in the volume of ischemic damage, was estimated to be 24 m̈g/ml during the initial 120 minutes after the middle cerebral artery occlusion. Treatment with D‐CPPene (15 mg/kg, plus an infusion of 170 m̈g/kg/min) initiated 1 hour after occlusion reduced the volume of ischemic brain damage in the cerebral cortex by 30%, but this response did not achieve statistical significance. Precise definition of dose dependency for the anti‐ischemic effects of NMDA antagonists and the therapeutic time window are influenced greatly by brain pharmacokinetics of the agents. Such data are crucial if the potent anti‐ischemic effects of NMDA antagonists observed in animals are to be translated into meaningful clinical evaluation of such agents in stroke and head trauma.
Short‐latency autogenic inhibition in patients with parkinsonian rigidity
Authors: Delwaide P. J. , Pepin J. L. , De Noordhout A. Maertens
Published: January 2005

The spinal Ib interneuron efficacy has been compared in 11 control subjects and 19 patients with parkinsonian rigidity. In normal subjects, gastrocnemius medialis nerve stimulation induces an inhibition of the soleus H reflex for 3 to 8 msec with a peak at 5 msec of 83.72 ± 7.28% of the control value of H reflex. In parkinsonian patients, inhibition is reduced or even replaced by facilitation, which also peaks at 5 msec. The departures from normal values correlate with rigidity intensity assessed by the Webster scale. Increase in rigidity is associated, first, with a reduction of inhibition and, from a score of 2 or more, with facilitation replacing the normal inhibition. In addition to providing an electrophysiological index of rigidity, reduction in autogenic inhibition might be one of the neurophysiological mechanisms underlying rigidity. In association with the known hyperactivity of the Ia inhibitory interneuron in Parkinson's disease, reduction of activity of Ib interneuron could be explained by an increased activity in the reticularis gigantocellularis nucleus; its efferent tracts both inhibit Ib interneurons and activate Ia interneurons.
Uhthoff's symptom in optic neuritis: Relationship to magnetic resonance imaging and development of multiple sclerosis
Authors: Scholl Georgina Bates , Song Hu‐Shien , Wray Shirley H.
Published: January 2005

Eighty‐one patients with a first attack of isolated optic neuritis, 40 with Uhthoff's symptom (Group 1) and 41 without (Group 2), were studied. All had a neurovisual examination, 74 of 81 patients had the pattern visual evoked potential recorded at rest, and 43 had magnetic resonance imaging brain scans. The pattern visual evoked potential P100 latency was prolonged, Group 1 with a mean of 136 ± 19 msec, Group 2 with a mean of 131 ± 19 msec (control subjects, 102 ± 5 msec; n = 84), and the P100 amplitude was reduced, without significant difference between the groups. Abnormal magnetic resonance imaging scans were present in significantly more patients in Group 1 (P < 0.025). Treatment of optic neuritis with corticosteroids had no effect on the evolution or duration of Uhthoff's symptom. Overall, 35 of 81 (43%) patients, followed for a mean of 3.5 years, developed multiple sclerosis. The incidence was significantly greater in Group 1 (p < 0.01). Uhthoff's symptom also correlated with a higher incidence of recurrent optic neuritis. We conclude that Uhthoff's symptom is a prognostic indicator for the early development of multiple sclerosis.
Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients
Authors: Ahlskog J. Eric , Richelson Elliott , Nelson Albert , Kelly Patrick J. , Okazaki Haruo , Tyce Gertrude M. , van Heerden Jon A. , Stoddard Susan L. , Carmichael Stephen W.
Published: January 2005

Binding of spiperone and 3‐quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was a clinically homogeneous group of patients: All remained predominantly responsive to levodopa, although with Marchked disability secondary to clinical fluctuations (short‐duration responses) and medication‐induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This finding may reflect medication‐induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergick cells, inferred to be present based on the prominent levodopa‐induced dyskinesias. Finally, receptor deficits could have also been a reflection of more widespread degenerative cerebral disease, although levodopa‐refractory symptoms were generally not pronounced in these patients.
Paravermal infarct and isolated cerebellar dysarthria
Authors: Amarenco Pierre , Chevrie‐Muller Claude , Roullet Etienne , Bousser Marchie‐Germaine
Published: January 2005

A patient with isolated cerebellar dysarthria is reported. Computed tomography showed a small infarct in the left paravermal zone of the rostal cerebellum (lobulus simplex and semilunaris superior) in the territory of the medial branch of the superior cerebellar artery. This patient demonstrates the important role of this area of cerebellum in the control of voice.
Alterations of dopaminergic and noradrenergic innervations in motor cortex in parkinson's disease
Authors: Gaspar Patricia , Duyckaerts Charles , Alvarez Chantal , Javoy‐Agid France , Berger Brigitte
Published: January 2005

The motor areas of the cerebral cortex contain dense dopaminergic and noradrenergic innervation in humans. We looked for changes of these innervations in cases with Parkinson's disease (PD). The density of fibers immunolabeled with tyrosine hydroxylase or dopamine‐beta‐hydroxylase was evaluated in the primary motor, premotor, and prefrontal cortical regions in 6 cases with PD and 7 control cases. Reductions of both noradrenergic and dopaminergic cortical innervations were observed, with similar magnitudes of reduction found in the motor and prefrontal regions of the cortex. Depletion of noradrenergic innervation was diffuse, involving all cortical laminae. Depletion of dopaminergic innervation was laminar specific, with the most significant reductions in layers I and II; reductions in layers V and VI were either less marked (prefrontal cortex) or not detectable (primary motor). The results suggest the existence of two separate mesocortical dopaminergic systems in humans, with the one distributing to upper cortical layers being preferentially involved in PD.