bluuebunny/crossref_metadata_2025 huggingface dataset:
Parkinsonism‐inducing neurotoxin MPP+: Uptake and toxicity in nonneuronal COS cells expressing dopamine transporter cDNA
Authors: Kitayama S. , Shimada S. , Uhl G. R.
Published: January 2005

Expression of a cloned dopamine transporter complementary DNA in COS cells allows these primate kidney cells to accumulate the parkinsonism‐inducing neurotoxin metabolite MPP+ (1‐methyl‐4‐phenylpyridinium) avidly, and MPP+ toxicity results. By documenting that the dopamine transporter can confer MPP+ sensitivity to nonneural cells, these results highlight the key role that this transporter could play in mechanisms underlying parkinsonism.
New magnetic resonance techniques for evaluating cerebrovascular disease
Authors: Fisher Marc , Sotak Christopher H. , Minematsu Kazuo , Li Limin
Published: January 2005

Magnetic resonance (MR) imaging of acute stroke has made important contributions to diagnosis. Several novel MR technologies, now in preclinical and clinical development, will contribute to stroke diagnosis and perhaps help to guide therapy. MR angiography is the most clinically advanced new MR technology and offers the clinician a method to image noninvasively the extra‐ and intracranial vasculature. Diffusion‐weighted MR imaging can demonstrate ischemic lesions quantitatively within minutes of onset in experimental stroke models, and human application is proceeding. Perfusion MR studies can reveal the presence or absence of cerebral perfusion in specific arterial territories. MR spectroscopy can assess tissue metabolites in vivo and reveal changes in these metabolites associated with ischemic injury. The combination of these new MR techniques should provide a plethora of information about the extent of ischemic lesions, associated vascular and perfusion deficits, and metabolic consequences. This information will afford the clinician the opportunity to assess and subtype ischemic stroke patients more rapidly and could be used to monitor therapeutic responses.
Impaired mesial frontal and putamen activation in Parkinson's disease: A positron emission tomography study
Authors: Playford E. D. , Jenkins I. H. , Passingham R. E. , Nutt J. , Frackowiak R. S. J. , Brooks D. J.
Published: January 2005

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free‐choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free‐choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateraputamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.
Absence of persistent infection with enteroviruses in muscles of patients with inflammatory myopathies
Authors: Leon‐Monzon Marta , Dalakas Marines C.
Published: January 2005

We searched for enteroviral nucleic acid sequences using the polymerase chain reaction and slot–blot hybridization in coded muscle biopsy specimens from 39 patients with active inflammatory myopathies (polymyositis, dermatomyositis, and inclusion–body myositis) and from 16 patients with other neuromuscular diseases, including patients with postpolio syndrome. For primers, we used sequences of the noncoding region at the 5′ end of the viral RNA. We failed to detect specific enteroviral nucleic acid sequences in the muscle biopsy specimens. Because this sensitive technique can amplify even low copy numbers of the viral genome, it appears unlikely that a persistent enteroviral infection is the cause of inflammatory myopathies.
Patterns of reactivity of human anti‐GM1 antibodies with spinal cord and motor neurons
Authors: Corbo Massimo , Quattrini Angelo , Lugaresi Alessandra , Santoro Maria , Latov Norman , Hays Arthur P.
Published: January 2005

Human anti‐GM1 antibodies from patients with lower motor neuron disease or predominantly motor neuropathy recognize carbohydrate determinants shared by GM1 and related glycolipids and glycoproteins, but the identity of the antigens to which they bind in tissue is unknown. We examined the binding of anit‐GM1 antibodies with differing fine specificities to spinal cord, isolated motor neurons, and dorsal root ganglia neurons in order to characterize the tissue antigens. All anti‐GM1 antibodies tested bound to the surface of bovine spinal motor neurons and immunostained the gray matter of unfixed sections of spinal cord. The staining was blocked by cholera toxin, which is specific for GM1, indicating that GM1 itself was the target antigen. Binding to white matter was more variable and depended on fixation and the fine specificities of the antibodies. The anti‐GM1 antibodies did not bind to dorsal root ganglia neurons in tissue sections or in culture. These studies suggest that the autoantibodies migh exert their effect, in part, by binding to GM1 on the surface of motor neurons, and that the absence of binding to dorsal root ganglia neurons might explain the lack of sensory abnormalities in affected patients.
Ipsilateral fast corticospinal pathways do not account for recovery in stroke
Authors: Palmer E. , Ashby P. , Hajek V. E.
Published: January 2005

We tested the hypothesis that in adult humans, recovery from stroke results from the emergence of ipsilateral, fastconducting corticospinal pathways. In 10 patients recovering from stroke, the unaffected hemisphere was stimulated with an electromagnet and changes in the firing probability of single biceps motor units were used to derive postsynaptic potentials in single biceps motoneurons. Stimuli sufficient to excite the neurons of the fast‐conducting corticospinal pathway (as shown by short‐latency facilitation of contralateral biceps motoneurons) did not produce short‐latency depolarization of ipsilateral biceps motoneurons. The hypothesis is therefore not supported.
The cortical lesion of Huntington's disease: Further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N‐methyl‐D‐aspartate lesions of rat cortex
Authors: Storey Elsdon , Kowall Neil W. , Finn Stephen F. , Mazurek Michael F. , Beal M. Flint
Published: January 2005

Huntingtons's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma‐aminobutyric acid (GABA)‐ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N‐methyl‐D‐aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA‐induced lesions showed striking sparing of parvalbumin‐positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA‐induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.
Calbindin‐D28K in the basal ganglia of patients with parkinsonism
Authors: Ito Hidefumi , Goto Satoshi , Sakamoto Shizuki , Hirano Asao
Published: January 2005

An immunohistochemical study was carried out to investigate the topographic distribution of calbindin‐D28K in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism‐dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin‐D28K immunoreactivity was identified in the medium‐sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin‐D28k expression in the basal ganglia of patients with PD and parkinsonism‐dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin‐D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin‐D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.
Adenosine: A potential mediator of seizure arrest and postictal refractoriness
Authors: During Matthew J. , Spencer Dennis D.
Published: January 2005

Adenosine is a potent inhibitory neuromodulator and has been proposed as an endogenous anticonvulsant. Depth electrodes modified to include a microdialysis probe were implanted for 10 to 16 days in the hippocampi of 4 patients with intractable complex partial epilepsy to test the hypothesis that during seizures extracellular adenosine reaches levels that may depress epileptiform activity. Samples were collected bilaterally at 3‐minute intervals before, during, and after a single, spontaneous‐onset seizure in each patient. All seizures commenced in one hippocampus and propagated to the contralateral hippocampus. Extracellular adenosine levels increased by 6‐ to 31‐fold with the increase significantly greater in the epileptogenic hippocampus. During seizures, levels of adenosine in the dialysate reached concentrations as high as 2.5 μM, reflecting extracellular concentrations of approximately 65 μM. Adenosine at concentrations of 40 to 50 μM depresses epileptiform activity in vitro, so the levels we report may suppress seizure activity in vivo. Moreover, adenosine levels remain elevated above basal values for the entire 18‐minute postical period. These data support the role of adenosine in mediating seizure arrest and postictal refractoriness and suggest that treatments which facilitate adenosine may be effective in preventing seizures.
Effectiveness of botulinum toxin administered to abolish acquired nystagmus
Authors: Leigh R. John , Tomsak Robert L , Grant Michael P. , Remler Bernd F. , Yaniglos Stacy S. , Lystad Lisa , Dell'Osso Louis F.
Published: January 2005

We injected botulinum toxin into the horizontal rectus muscles of the right eyes of 2 patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In 1 patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic‐adaptive changes in response to paresis caused by the botulinum toxin. Such plastic‐adaptive changes and direct side effects of the injections—such as diplopia and ptosis—may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment.
Blood‐brain barrier abnormalities in acquired immunodeficiency syndrome: Immunohistochemical localization of serum proteins in postmortem brain
Authors: Petito Carol K. , Cash Kevin S.
Published: January 2005

Abnormalities in the blood‐brain barrier (BBB) may be important in mediating some of the tissue damage that accompanies human immunodeficiency virus (HIV) infection of the brain, as well as in facilitating viral entry into the central nervous system. Accordingly, immunohistochemical detection of fibrinogen (FIB) and immunoglobulin G (IgG) was used as a marker of vascular permeability in formalin‐fixed, paraffin‐embedded brains of patients with acquired immunodeficiency syndrome (AIDS) who had HIV encephalitis (HIVE) (n = 17) and those who did not have HIVE (n = 16); nonimmunosuppressed patients served as control subjects (n = 22). The sex ratios and postmortem intervals were similar in all groups (p < 0.05), but the age of the two AIDS groups were younger than the control group (43.2 and 40.9 versus 62.5 yr; p < 0.05). The two AIDS groups had higher immunostaining for FIB and IgG than the control group (p < 0.001 and p < 0.0001, respectively) but did not differ from one another. Furthermore, the two AIDS groups had a significantly higher incidence of combined extravasation of both FIB and IgG, whereas the control group had a significantly higher incidence of negative staining for both proteins (p < 0.002). More than 95% of the microglial nodules of HIV were negative for serum proteins; however, all focal lesions with tissue necrosis, including lymphoma, opportunistic infections, and HIV (rarely), contained extravasated serum proteins. These results indicate that a diffuse BBB leak is present in approximately 50% of all patients with AIDS at the time of autopsy and may be seen in the absence of any other brain pathology, including HIVE. In contrast, focal lesions, including those of HIVE, are associated with BBB changes only when necrosis is present. The pathogenesis of the diffuse leak is unknown but may be related to circulating cytokines. Diffuse BBB breakdown may contribute not only to facilitated viral entry into brain, but also to the diffuse myelin pallor and gliosis common to all patients with AIDS.
Disease‐specific patterns of locus coeruleus cell loss
Authors: German Dwight C. , Manaye Kebreten F. , White Charles L , Woodward Donald J. , McIntire Donald D. , Smith Wade K. , Kalaria Rajesh N. , Mann David M. A.
Published: January 2005

Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral‐caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical‐projecting locus coeruleus cells and spares the caudal, noncortical‐projecting cells.
Neuropsychological features of familial Alzheimer's disease
Authors: Swearer Joan M. , O'Donnell Brian F. , Drachman David A. , Woodward Beatrice M.
Published: January 2005

It has been proposed that early‐onset familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (AD) have different causes, with FAD due to a single dominant gene with disease onset before the sixth decade, whereas sporadic AD has a later onset and is not associated with a dominant pattern of inheritance. Given these differences, we questioned whether these etiologically distinct forms of AD also differ neuropsychologically. In this study we performed neuropsychological evaluations on patients from two well‐documented families with FAD and a group of patients with sporadic AD. The groups were matched on global disease severity at entry. Two groups of education and age‐matched normal controls were recruited for comparison. The groups were analyzed for psychometric findings and pattern of deficits. Both patients with FAD and patients with sporadic AD showed a similar pattern of neuropsychological impairment relative to age‐matched controls, i.e., mildly to moderately impaired verbal performance and concentration, severely slowed psychomotor speed, and severely impaired delayed recall of verbal material. There were no differences in pattern suggestive of disproportionately severe anomia, amnesia, agnosia, or apraxia in the early onset FAD group, as has been reported previously.
Multiple sclerosis in 54 twinships: Concordance rate is independent of zygosity
Authors:   French Research Group on Multiple Sclerosis
Published: January 2005

In a large population‐based multiple sclerosis (MS) sample (n = 7,951), 116 twins were identified (1.4%), of which it was possible to contact 97. In 27 pairs, the twin of the patient with MS was dead. Among the 70 remaining pairs, 16 were excluded because either the index patient or their twin did not accept protocol requirements. The final sample included 54 pairs. Twin zygosity was determined by DNA fingerprint analysis. We found 17 monozygotic pairs and 37 dizygotic pairs. One of the 17 monozygotic pairs (5.9%) and 1 of the 37 dizygotic pairs (2.7%) were concordant for MS. In 42 of the clinically unaffected twins, magnetic resonance imaging (MRI) of the brain was performed, and 9 scans were classified as indicative of MS. Three of these 42 patients had abnormal visual‐evoked potentials, but all 3 had normal MRI scans. The overall proportion of pairs in which the co‐twin had some form of clinical, radiological, or electrophysiological abnormality was approximately 30%; this proportion was independent of zygosity.
The postpolio syndrome: No evidence for poliovirus persistence
Authors: Melchers Willem , de Visser Marianne , Jongen Peter , Van Loon Anton , Nibbeling Ria , Oostvogel Paul , Willemse Diana , Galama Jochem
Published: January 2005

To investigate the possibility of poliovirus persistence in patients with the postpolio syndrome, we examined skeletal muscle biopsy specimens, cerebrospinal fluid specimens, and sera for the presence of poliovirus RNA by the polymerase chain reaction, and for IgM antibodies by a poliovirus type‐specific IgM antibody‐capture enzyme‐linked immunosorbent assay. In none of these specimens was poliovirus RNA or a poliovirus type‐specific IgM response detected. These results argue against the hypothesis that poliovirus persists in patients with the postpolio syndrome and plays a role in the pathogenesis of the postpolio syndrome.
Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine
Authors: Jenkins I. H. , Fernandez W. , Playford E. D. , Lees A. J. , Frackowiak R. S. J. , Passingham R. E. , Brooks D. J.
Published: January 2005

Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still “off” but receiving a subcutaneous apomorphine infusion, and when switched “on” with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the “off” and “on” states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the “off” state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine‐treated patients with PD provides further evidence for the role of this structure in generating motor programs.
Platelet mitochondria function in Parkinson's disease
Authors: Krige David , Carroll Maria T , Cooper J. Mark , Marsden C. David , Schapira Anthony H. V. ,   (The Royal Kings Queens Parkinson Disease Research Group)
Published: January 2005

There is increasing evidence that defective function of the mitochondrial enzyme NADH CoQ reductase (complex I) is involved not only in l‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine (MPTP) toxicity, but also in idiopathic Parkinson's disease (PD). Complex I deficiency has been identified in PD substantia nigra and appears to be disease‐specific and selective for the substantia nigra within the central nervous system. We describe a method for preparation of an enriched mitochondrial fraction from 60 mL blood. Using this technique, we analyzed respiratory chain function in 25 patients with PD and 15 matched control subjects. We confirm a previous report of a specific complex I deficiency in PD platelet mitochondria. Although there was a statistically significant decrease in complex I activity in the PD group compared with the control group (p = 0.005), the defect was mild (16%); it was not possible to distinguish PD from control values on an individual basis. This deficiency is not detectable in platelet whole‐cell homogenates, presumably reflecting the relative insensitivity of this preparation and the limited decrease in complex I activity in PD. The presence of a mild complex I defect in platelets together with a more severe defect in substantia nigra suggests either that the pharmacological characteristics shared by these two tissues render them susceptible to a particular toxin or toxins, or that the defect is widely distributed and other biochemical events enhance the deficiency in substantia nigra. Evidence for a complex I defect in platelet mitochondria from patients with PD supports the proposition that this biochemical deficiency may have some role in the cause of dopaminergic cell death in this disorder.
Relative sparing of nitric oxide synthase–containing neurons in the hippocampal formation in Alzheimer's disease
Authors: Hyman Bradley T. , Marzloff Kristin , Wenniger Julia J. , Dawson Ted M. , Bredt David S. , Snyder Solomon H.
Published: January 2005

Nitric oxide (NO) is an endogenous neuromodulator that may mediate neurotoxic effects of glutamate. NO‐synthesizing neurons are, however, resistant to NO‐ and glutamate‐induced neurotoxicity. We now show that NO synthase neurons are selectively spared in patients with Alzheimer's disease, even in a severely affected region of the brain such as the hippocampal formation.
Expression of 65‐kd heat shock proteins in the inflammatory myopathies
Authors: Hohlfeld Reinhard , Engel Andrew G.
Published: January 2005

In normal muscle, 65‐kd heat shock proteins (hsp) were detected on capillary endothelial cells, the mural elements of larger vessels, and some intracellular organelles, probably mitochondria. In the inflammatory myopathies, the 65‐kd hsp were detected on inflammatory cells, degenerating and regenerating fibers, and on many but not all nonnecrotic muscle fibers invaded by T cells. The expression of the 65‐kd hsp may be an immunenonspecific response to cellular “stress” but hsp determinants could possibly also serve as autoantigen(s) recognized by autoreactive T cells.
Familial rectal pain: A type of reflex epilepsy?
Authors: Schubert Romaine , Cracco Joan B.
Published: January 2005

We studied 2 members of a family suffering from paroxysmal attacks elicited by tactile stimuli. The attacks consist of burning pain of the stimulated body part, followed by either complete collapse or tonic posturing. Noxious stimuli provoke episodes regardless of their somatic location, whereas it is only necessary for nonnoxious stimuli to be applied to specific trigger zones, such as the rectum, to provoke attacks. Episodes are most commonly precipitated by bowel movement, leading to extreme fear of defecation and resultant fecal retention. An ictal electroencephalographic video recording revealed only slowing of the background; however, serum prolactin was significantly elevated postictally. The attacks were completely suppressed by carbamazepine and resumed on discontinuing the medication. These attacks may represent a form of reflex epilepsy manifested by autonomic nervous system dysfunction.
3‐Methylglutaconic aciduria in “optic atrophy plus”
Authors: Costeff Hanan , Elpeleg Orly , Apter Naomi , Divry Priscille , Gadoth Natan
Published: January 2005

Behr's syndrome consists of recessively inherited infantile optic atrophy, together with chronic neurological disturbances such as ataxia, extrapyramidal dysfunction, and juvenile spastic paresis. This syndrome was found to be relatively common among Iraqi Jews. For our study, 18 such patients underwent metabolic study. All 18 showed abnormally elevated excretion of 3‐methylglutaconic acid in their urine. The basic enzymatic defect is as yet unknown. We recommend that patients with early optic atrophy, and especially those with motor dysfunction, be examined for this organic aciduria.
Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation
Authors: Reich Jeffrey B. , Sierra John , Camp Walter , Zanzonico Patrick , Deck Michael D. F. , Plum Fred
Published: January 2005

Current Concept of brain herniaton have depended largely on correlating clinical sings and symptoms with indirect radiographic studies and the results of postmortem neuropathology. This article describes measurments on midsagittal magnetic resonance imaging (MRI) scans that distinctly define normal and abnormal rostral–caudal relationships between the diencephalic–mesencephalic junction and the plane of the tentorial incisura, herein termed the incisural line. We similarly provide quantitative MRI scan measurments relating the cerebellum and the plane of the foramen magnum, termed the foramen magnum line. Measurements from 156 midsagittal and 63 coronal MRI scans performed on 123 normal adults, placed the iter of the aqueduct 0.2 ± 0.8 mm (mean ± SD) below the incisural line and the cerebeller tonsils 0.1 ± 2.1 mm below the foramen magnum line. Defining 2 SD from thses norms as abnormal, 23 patients with intracranial mass or obstructive lesions showed 4 distinct patterns of brain herniation, i.e., upward or downward transtentorial shift with of without accompanying cerebellar tonsillar herination. Five patients with Posterior fossa masses demonstrated displacement of the iter above the incisura ranging from 1.6 to 6.3 mm. Eighteen patients with supratentorial masses demonstrated displacements of the iter ranging from 2.0 to 11.0 mm below the incisura. Two‐third of patients with upward and one‐half of those with downward transtentorial shift had concurrent tonsillar herination. In acute illnesses, MRI scan changes anticipated or confirmed clinical signs of brain herniation. In chronic cases, clinical and MRI scans correlated less well, with MRI sometimes revealing major degrees of anatomical herniation well in advance of clinical abnormalities.
The influence of muscular lengthening on cramps
Authors: Bertolasi L. , De Grandis D. , Bongiovanni L. G. , Zanette G. P. , Gasperini M.
Published: January 2005

Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contracion or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hyposthesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism.
Synapse loss in the temporal lobe in Alzheimer's disease
Authors: Scheff Scheff W. , Price Douglas A.
Published: January 2005

The temporal lobe is a well‐documented area showing neuropathological and neurochemical changes in Alzheimer's disease (AD). Autopsy tissue was obtained from the superior temporal (Brodmann area 22) and the middle temporal (Brodmann area 21) regions of the cortex from patients with AD (n = 10; postmortem time < 13 hr) and age‐matched control subjects (n = 10; postmortem time < 13 hr). Ultrastructural examination of the tissue revealed a highly significant AD‐related decline in synaptic numbers in lamina III abd V in both the superior and the middle temporal gyrus. Both normal control and AD tissue samples demonstrated a significant negative correlation between the number of synapses and the synapse size, as indexed by the length of the postsynaptic density. This change in synaptic size appears to compensate for the loss of synaptic numbers when viewed in terms of total synaptic contact area. Although the AD tissue showed an average 30% decline in synaptic numbers, the total synaptic contact area remained largely unchanged in both regions of the cortex. There were no significant correlations with age, postmortem time, or number of plaques observed in these areas. The loss of synaptic contacts in AD does not appear to be isolated to a particular cortical region or lamina.
Campylobacter jejuni strains from patients with guillain‐barré syndrome belong mostly to penner serogrpup 19 and contain β‐N‐acetylglucosamine residues
Authors: Kuroki Shigekazu , Saida Takahiko , Nukina Massafumi , Haruta Tsunekazu , Yoshioka Mieko , Kobayashi Yutaka , Nakanishi Hisao
Published: January 2005

Campylobactor jejuni was isolacted from stool cultures from 14(30%) of 46 partients with Guillain‐Barré syndrome and from 6(1.2%) of healthy persons, and the difference was highly significant (P<0.0001). In addition, serological evidence of recent. C. Jejuni infection. Ten of 12(83%) isolated from partients with Guillain‐Barré syndrome belonged to Penner serogroup 19, which is a rare serogroup in sporadic patients with C. Jejuni enterties. In the lection typing stude, all serogroup 19 strains from patients with Guillain‐Barré syndrome patients with Guillain‐Barré syndrome were shown to contain terminal b̃‐N‐acetylglucosamine residues on their cell surface, bur serogroup 19 strains from patients with enteritis were not.
Retinal ganglion cells in Alzheimer's disease and aging
Authors: Curcio Christine A. , Drucker David N.
Published: January 2005

Optic nerve and retinal gangliion cell (GC) degeneration are possible explanations for the poor visul function reported in patients with Alzheimer's disease (AD). We investigated whether GC loss could be attributed to AD compared with control subjects by measuring the spatial density of GC(vells/mm2) with methods previously used to analyze the GC distribution of young normal retinas. Retinas from 4 autopsy‐confirmed, severely demented partients with AD and 4 age and sex‐matched control subjects (ages, 66‐86 yr for both groups) withould history of dementing or ocular disease were prepared as unstained whold mounts. Therer was no evidence for loss of GC within the central 43 degrees of vision in patients with AD. The densityof GC subserving the central 11 degrees of vision was reduced by one‐fourth in both AD and control eyes compared with retinas from young adults, as was GC density in a wedge of nasal retina. This loss may contribute to deficits in visual function found in aged individuals, whether or not they have dementia.
Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis
Authors: Ptacek Louis J. , Gouw Launce , Kwieciński Hubert , McManis Philip , Mendell Jerry R. , Barohn Richard J. , George Aflfred L. , Barchi Rebert L. , Robertson Margaret , Leppert Mark F.
Published: January 2005

Clinical and electrophysiological data have outlined a spectrum of similar yet distinct periodic paralyses, including potassium‐sensitive (hyperkalemic periodic paralysis [HYPP]) and temperature‐sensitive (paramyotonia congenita [PC]) forms. Recent work has revealed that these disorders result from allelic defects in the x‐subunit of the adult, human skeletal muscle sodium channel. We report an additional mutation, a leucine ‐ arginine substirution in the ss segment of domain 4 (L1433R), that results in the PC phenotype. Five other HYPP and PC families have been ascertained, and previously reported sodium channel mutations have been identified in each. Characterization of these mutartions and phenotypic variations in such familes will contribute to the understanding of sodium channel structure and function relationships, as well as channel malfunction in the periodic paralyses.
Acute motor axonal neuropathy: A frequent cause of acute flaccid paralysis in China
Authors: McKhann G. M. , Cornblath D. R. , Griffin J. W. , Ho T. W. , Li C. Y. , Jiang Z. , Wu H. S. , Zhaori G. , Liu Y. , Jou L. P. , Liu T. C. , Gao C. Y. , Mao J. Y. , Blaser M. J. , Mishu B. , Asbury A. K.
Published: January 2005

In northern China, annual epidemics of acute‐onset flaccid paralysis diagnosed clinically as Guillain‐Barré syndrome have been recognized for at least 20 years. On the basis of an historical analysis of more than 3,200 patients, distinctvie features include most cases occurring during the summer months among children and young adults, most of whom reside in rural areas. Of 90 patients with acute flaccid paralysis, 88 had a distinctive pattern that shares clinical and cerebrospinal fluid findings with demyelinating Guillain‐Barré syndrome, but that differs from Guillain‐Barré syndrome physiologically and pathologically. The clinical course is marked by rapidly progressive ascending tetraparesis, often with respiratory failure, but without fever, systemic illness, or sensory involvement. Cerebrospinal fluid is acellular, and elevations of protein content occur in the second or third week of illness. Electrodiagnostic studies show normal motor distal latencies and limb conduction velocities, but reduced compound muscle action potential amplitudes. Sensory nerve action potentials and, when elicitable, F waves are within the range of normal. Recovery is usually good. Autopsy studies have shown Wallerian‐like degeneration of motor fibers. These studies establish that this is a distinctive syndrome, distinguishable from poliomyelitis and demyelinating Guillain‐Barré syndrome.
Human immunodeficiency virus type 1 infection of the nervous system: Pathogenetic mechanisms
Authors: Epstein Leon G. , Gendelman Howard E.
Published: January 2005

Human immunodeficiency virus type 1 (HIV‐1) infection of the central nervous system is associated with characteristic virological, clinical, and neuropathological findings in adults and children. Productive infection in the brain and spinal cord occurs in blood‐derived macrophages, resident microglia, and multinucleated giant cells. Previous work implicated indirect mechanisms for neurotoxicity by HIV‐1 gene products or by factors secreted from HIV‐1‐infected macrophages. However, this cannot explain the paradox between the small numbers of infected cells and the widespread tissue pathology. Based on recent studies from our laboratories, we suggest that HIV‐1‐infected macrophages can initiate neurotoxicity, which is then amplified through cell‐to‐cell interactions with astrocytes. Macrophageastrocyte interactions produce cytokines tumor necrosis factor‐α and interleukin‐1b̃ and arachidonic metabolites that cause astroglial proliferation and neuronal injury. Inevitably, the astrogliosis serves to amplify these cellular processes while brain infection maintains itself in macrophage and microglia and possibly in astrocytes (by restricted infection). These findings, taken together, provide fresh insights into how low numbers of productively infected cells could elicit progressive and devastating neurological impairment during HIV‐1 disease, and suggest therapeutic strategies to interrupt the pathological process.
Expression of c‐fos and c‐jun family genes after focal cerebral ischemia
Authors: An Gang , Lin Teng‐Nan , Liu Jia‐Shou , Xue Juan‐Juan , He Yong‐Yue , Hsu Chung Y.
Published: January 2005

The expression of the protooncogenes, c‐fos, jun B, c‐jun, and jun D was investigated in a rat focal cerebral ischemia model by Northern analysis and in situ hybridization. Severe ischemia (reduction of regional blood flow by 88‐92%) in this model is confined to cerebral cortex irrigated by the right middle cerebral artery. Ischemia for 30 minutes, which caused only slight cortical damage (infarct size, <10 mm3), induced both jun B and c‐fos mRNAs exclusively in the right cerebral cortex. Ischemia for 90 minutes, which led to large cortical infarction (infarct size, >140 mm3), also induced the expression of these two genes in the right cerebral cortex as well as the ipsilateral hippocampus. The latter sustained very mild ischemia (reduction of regional blood flow by 10–20%). The coinduction of jun B and c‐fos expression occurred immediately after reperfusion and peaked at 60 minutes after reperfusion. The expression of c‐jun was enhanced in a similar pattern, but at a much lower magnitude. In contrast, no change in jun D expression was observed. Nuclear run‐on assays indicated that the increase in c‐fos, jun B, and c‐jun mRNA levels was due to the increase of transcription rate in these genes. Mobility shift assays showed a basal DNA binding activity of transcription factor AP‐1 in the right cerebral cortex. Ischemia for 30 or 90 minutes followed by reperfusion for 4 hours resulted in a four‐ to sixfold increase of AP‐1 binding activity. The enhanced DNA binding activity persisted for as long as 24 hours, These results suggest that the enhanced expression of AP‐1, a general transcription factor, may play a role in the alteration of gene regulation in the ischemic cortex.
Defecatory function in Parkinson's disease: Response to apomorphine
Authors: Edwards L. L. , Quigley E. M. M. , Harned R. K. , Hofman Ruth , Pfeiffer R. F.
Published: January 2005

We evaluated the effects of the dopaminergic agent apomorphine on defecation and anorectal function in patients with Parkinson's disease (PD). A gastrointestinal symptom survey, extrapyramidal assessment, defecating proctogram, and anorectal manometric study were performed in 8 subjects with PD. Basal studies showing abnormalities were repeated following apomorphine administration. Prior defecographic abnormalities were normalized following apomorphine injection in 1 of 3 subjects and significant improvements in manometric parameters were observed in all 5 subjects who underwent repeat anorectal manometry. We conclude that apomorphine can correct anorectal dysfunction in PD, and that these abnormalities may be a consequence of dopamine deficiency secondary to the PD process. These findings may also have therapeutic implications.
Experimental paraprotein neuropathy, demyelination by passive transfer of human IgM anti‐myelin‐associated glycoprotein
Authors: Tatum Arthur H.
Published: January 2005

Circulating monoclonal IgM antibodies that react with myelin‐associated glycoprotein are strongly associated with a specific type of human peripheral nerve demyelination. There has been great interest in this syndrome because, if the paraprotein could be shown to cause the demyelination, then it would be the first proven example of antibody‐mediated demyelination in humans. Systemic transfusion of chickens with monoclonal IgM antibody isolated from one of these patients produced peripheral demyelination highly characteristic of the human syndrome. The experimental lesion consists of segmental demyelination and remyelination with minimal inflammation, specific antibody bound to myelin, and widening of the myelin lamellae. In the experimental model, antibody is concentrated in specialized myelin structures, the nodes of Ranvier, and Schmidt‐Lanterman incisures, suggesting that myelin‐associated glycoprotein may be the antigenic target in vivo. This demonstration that human myelin‐associated glycoprotein antibodies cause demyelination in vivo is the final information needed to prove that this type of human demyelination is antibody mediated. This strengthens the proposition that nerve antibodies, present in other human neurological syndromes, may also cause disease.
Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors
Authors: Janus Todd J. , Kim E. Edmund , Tilbury Roy , Bruner Janet M. , Yung W. K. Alfred
Published: January 2005

In patients with malignant gliomas, [18F]fluorodeoxyglucose positron emission tomography (FDG‐PET) may discriminate tumor progression from radionecrosis. We evaluated data from 50 patients undergoing FDG‐PET for suspicion of tumor progression. Forty‐nine were treated with surgery, 48 with radiotherapy, and 37 with chemotherapy. Twenty‐one had intensive radiotherapy with either three daily treatments in two 5‐day periods and intravenous carboplatin (17) or interstitial brachytherapy or stereotactic radiotherapy. Twenty underwent surgery after magnetic resonance imaging/FDG‐PET; 9 demonstrated increased uptake of FDG and evidence of tumor, whereas 6 had decreased uptake and no evidence of tumor. In 5 patients, there was no correlation (all had intensive radiotherapy). In 17 patients who received bromodeoxyuridine intravenously just before surgery, the bromodeoxyuridine labeling index corresponded to the histological appearance in all but 2 patients (both had received intensive radiotherapy). In 30 patients without surgery, decreased uptake of FDG suggested prolonged survival; increased uptake of FDG did not predict survival. Eight of 10 with intensive radiotherapy had decreased label uptake. We conclude FDG‐PET for evaluation of patients with possible recurrent tumors requires more study. In patients with intensive radiotherapy, FDG‐PET results cannot be correlated accurately with tumor progression.
Immune‐mediated demyelination
Authors: Hartung Hans‐Peter
Published: January 2005

The Guillain‐Barré syndrome (GBS) and multiple sclerosis (MS) are though to result from aberranr immune responses to myelin antigens. Recent evidence to implicate the cytokine tunmor necrosis factor‐α(TNF‐α) and the intercellular adhesion molecule‐1(ICAM‐1) in the pathogenesis of these disorders is reviewed. In GBS, elevared serum concentrations of TNF‐α are detectable in 20 to 50% of patients. TNF‐α released from autoreactive T cells, macrophages, or microglia may contribute to inflammatory demyelinative processes by upregulating the expression of recognition molecules on antigen‐presenting cells; by cytotoxic damage to endothlium; by stimulating the secretion of inflammatory mediators; by directly injuring the myelin sheath; or by interfering with impluse propagation. Its pathogenic potential in GBS is underscored by findings in experimental autoimmune neuritis. Soluble ICAM‐1, originating from T cells, macrophages, endothelium, or glial cells, circulates at increases concentrations in serum and cerebrospinal fluid of patients with active MS. ICAM‐1 may be crucially involved in the migration of autoreactive T lymphocytes from blood to brain. Whether ICAM‐1 can serve as a maker of acute inflammatory events in ms associated with clinical relapses warrants further investigation. TNF‐α and ICAM‐1 coud be targets for antigen nonspecific treatment approaches to the inflammatory demyelinating diseases GBS and MS.