bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral glucose metabolism in the Lennox‐Gastaut syndrome
Authors: Theodore William H. , Rose Douglas , Patronas Nicholas , Sato Susumu , Holmes Mark , Bairamian Dikran , Porter Roger J. , Chiro Giovanni Di , Larson Steven , Fishbein Donn
Published: January 2005

We used positron emission tomography with fluorine 18–labeled 2‐deoxyglucose to study cerebral glucose metabolism in 10 patients with Lennox‐Gastaut syndrome who had normal neuroradiological studies. The scans showed decreased metabolic rates relative both to those in the caudate nucleus and to normal control values in 3 patients whose seizures began before the age of 1, as well as in a patient with hyperprolinemia. No patient had a region of persistent focal hypometabolism. Metabolic rates increased in parallel with increased electroencephalographic discharges in 1 patient; 3 patients had lower metabolic rates when the electroencephalogram showed epileptiform discharges and while the patients were taking barbiturates.
Defective biosynthesis of proteolipid protein in pelizaeus‐merzbacher disease
Authors: Koeppen Arnulf H. , Ronca Nicholas A. , Greenfield Edward A. , Hans Mary B.
Published: January 2005

The brain of an 18‐year‐old patient with Pelizaeus‐Merzbacher disease was examined by standard neuropathological and biochemical methods and by immunocytochemical and immunochemical techniques. Analysis revealed a lack of myelin‐specific lipids, but showed a residual immunoreactivity for myelin basic protein, myelin‐associated glycoprotein, and 2,3‐cyclic nucleotide‐3‐phosphodiesterase. Examination by immunocytochemistry and enzyme‐linked immunosorbent assay showed an absence of proteolipid apoprotein (lipophilin). The peripheral nervous system was normal. Pelizaeus‐Merzbacher disease in humans shares many neuropathological and biochemical features with X‐linked mutations in animals, e.g., the jimpy mouse and myelin‐deficient rat. The specificity of this protein deficiency in Pelizaeus‐Merzbacher disease gains additional support from the recent mapping of the lipophilin gene to the human X chromosome.
Absence seizures in children: Clinical and electroencephalographic features
Authors: Holmes Gregory L. , McKeever Mark , Adamson Megan
Published: January 2005

The clinical and electroencephalographic (EEG) features of absence seizures in children were evaluated using EEG frequency modulation radiotelemetry and videotape monitoring. The only seizures evaluated were those with a spike‐and‐wave or multiple spike‐and‐wave duration lasting at least 3 seconds. A total of 926 absence seizures (426 typical, 500 atypical) were reviewed in 54 patients. Abnormal interictal EEGs, multiple seizure types, mental retardation, or developmental delay were more likely in patients with atypical absence seizures than in patients with typical absence seizures. Both types of absence seizures usually had a clear onset and cessation. Atypical absence seizures lasted significantly longer than did typical absence seizures. Automatisms occurred more frequently in typical absence seizures than in atypical ones, while decreases in postural tone or tonic activity occurred more frequently in atypical absence seizures. Receptive and expressive speech were retained in some patients during both types of seizures. This study demonstrates that typical and atypical absence seizures are not discrete entities but rather form a continuum. No single clinical feature can adequately distinguish the two seizure types.
Clinical features and mechanism of occipital infarction
Authors: Pessin Michael S. , Lathi Ellen S. , Cohen Maurice B. , Kwan Eddie S. , Hedges Thomas R. , Caplan Louis R.
Published: January 2005

To clarify the clinical features and mechanism of infarction in the posterior cerebral artery territory, we investigated 35 consecutive patients who presented with homonymous visual field defects and occipital infarction documented by computed tomography. Cerebral angiographic findings in 23 patients, and the clinical features of rare transient ischemic attacks and maximal deficit occurring at stroke onset, were consistent with embolism of the posterior cerebral artery. Visual field defects were the only neurological abnormality in 17 patients; the remainder had additional findings. Three patients had a major brainstem stroke. Stroke in the posterior cerebral artery territory was found in a heterogeneous group of patients, although embolism was the most common stroke mechanism. Several distinct patient groups were identified: cardiac source embolism (10 patients), vertebrobasilar atheroma with local embolism (6), migraine (5), systemic illness with presumed coagulopathy (3), and “unknown source embolism” after negative cardiac investigation (11 patients). During follow‐up, 26 patients had no further neurological events (the majority on anticoagulation or antiplatelet treatment), 3 suffered new strokes, and 6 died.
Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease
Authors: Perry Thomas L. , Yong Voon Wee , Bergeron Catherine , Hansen Shirley , Jones Karen
Published: January 2005

We measured the contents of amino acids and related amino compounds in autopsied brain from 22 patients with Alzheimer's disease (AD) and in cortical biopsy specimens from 2 other patients. The diagnosis of AD was established neuropathologically in all 24 patients by the presence of both neurofibrillary tangles and neuritic plaques in neocortex. The mean contents of γ‐aminobutyric acid (GABA), and of the GABA dipeptide homocarnosine, were significantly reduced in frontal and occipital cortices and in hippocampus of the autopsied brains of AD patients compared to control patients without neurological disease. However, GABA contents were normal in frontal cortex in biopsy samples from 2 patients. Phosphoethanolamine contents were significantly reduced at autopsy in frontal and occipital cortex, and in the substantia innominata. We found no evidence of a deficiency of glutamate, aspartate, or taurine in AD brain, as has been claimed. Glutathione contents and glutathione transferase activities were normal in frontal cortex and substantia innominata. The mechanism of neuronal death in patients with AD is unlikely to involve either insufficient synthesis of glutathione or failure to conjugate free radicals with glutathione.
Central sleep apnea and partial obstruction of the upper airway
Authors: Guilleminault Christian , Quera‐Salvá Maria Antonia , Nino‐Murcia German , Partinen Markku
Published: January 2005

Seven men with central sleep apnea underwent polygraphic monitoring during sleep for at least 3 nights, in combination with other tests. Five patients had complaints of disturbed sleep; the other 2 were selected because they had central sleep apnea caused by bilateral brainstem lesions. The first 5 had a small upper airway, documented by cephalometric roentgenograms. Nasal continuous positive airway pressure, administered to improve the suspected respiratory load during sleep, eliminated the central sleep apnea in the first 5 patients but had, as expected, no positive effect on the central apnea of the 2 patients with brainstem lesions.
Oculogyric crisis: A syndrome of thought disorder and ocular deviation
Authors: John Leigh R. , Foley Joseph M. , Remler Bernd F. , Civil Richard H.
Published: January 2005

In 3 patients who suffered oculogyric crises, mental changes accompanied upward deviation of the eyes. In 1 patient, whom we studied in detail, the mental disturbance consisted of a disorder of attention in which pathological fixation of a thought occurred. During the period of upward eye deviation, all functional types of conjugate eye movements were present in the upper field of gaze, suggesting an imbalance of the vertical gaze–holding mechanism. The eyes could be driven down only by a combined blink and downward saccade. Both the thought disorder and the ocular deviation responded promptly to anticholinergic agents. We propose that the disorders of thought and eye movement in oculogyric crisis are linked by a pharmacological imbalance common to both.
Alzheimer's disease: Glutamate depletion in the hippocampal perforant pathway zone
Authors: Hyman Bradley T. , Van Hoesen Gary W. , Damasio Antonio R.
Published: January 2005

The perforant pathway is the primary source of cortical input to the hippocampal formation. Its cells of origin, in the entorhinal cortex, are destroyed in Alzheimer's disease. Because the principal neurotransmitter of the perforant pathway's excitatory action is thought to be glutamate, we microdissected a portion of the pathway's terminal zone and assayed the excised tissue for glutamate. There was an 83% decrease in the level of free glutamate in subjects with Alzheimer's disease as compared to control subjects not affected by dementia (p < 0.005). We believe that this diminution in the glutamate content is a direct neurochemical correlate of perforant pathway destruction and that disruption of this crucial corticolimbic pathway contributes to the memory dysfunction in Alzheimer's disease.
Multifocal CNS demyelination following peripheral inoculation with herpes simplex virus type 1
Authors: Kastrukoff Lorne F. , Lau Allen S. , Kim Seung U.
Published: January 2005

The peripheral inoculation of herpes simplex virus type 1 (HSV 1) in experimental animals induces central nervous system (CNS) demyelinating lesions, but the potential relevance of this model to multiple sclerosis is lessened by the unifocal nature of the lesion. In this study, inbred strains of mice were selected on the basis of varying resistance to mortality following lip inoculation with virus. A spectrum of CNS pathology was observed, ranging from focal collections of inflammatory cells at the trigeminal root entry zone in resistant strains (C57BL/6J), to unifocal demyelinating lesions in moderately resistant strains (BALB/cByJ), to multifocal demyelinating lesions throughout the brain in susceptible strains (A/J). Findings from viral titration studies of the CNS support a direct cytolytic effect of virus in the development of demyelinating lesions at the trigeminal root entry zone but cannot exclude an immune‐mediated component. Furthermore, 50% tissue‐culture‐infective doses, immunofluorescence, and electron microscopic studies of primary cultures of oligodendrocytes, derived from the three strains of adult mice, identify differences in resistance to HSV 1 infection in vitro, suggesting that differences at this level may also contribute to the pathological appearance. Multifocal lesions in A/J mice were first observed when the infectious virus could no longer be isolated from the CNS and may be the result of an immune‐mediated process “triggered” by the acute CNS infection in susceptible strains of mice.
Ataxia after severe head injury: The pathological substrate
Authors: Susan Chester C. , Reznick Barry R.
Published: January 2005

Ataxia is a common finding in patients who have recovered from severe head injury. This report delineates the clinical and pathological findings in a patient who recovered from a head injury but was left with ataxia of gait. A lesion of the superior cerebellar peduncle, demonstrated post mortem 2½ years after injury, was the only explanation for the ataxia. This lesion is part of the spectrum of changes seen in diffuse axonal injury thought to be due to shearing forces which tear white matter at the time of the initial injury.
Giant axonal neuropathy: Correlation of clinical findings with postmortem neuropathology
Authors: Thomas C. , Love S. , Powell H. C. , Schultz P. , Lampert P. W.
Published: January 2005

We report the clinical and postmortem neuropathological findings in a case of long‐standing giant axonal neuropathy. The patient, a caucasian male with kinky hair, was first seen at 4 years of age because of increasing unsteadiness of gait. Clinical examination showed nystagmus, cerebellar ataxia, distal sensory loss, and weakness. A sural nerve biopsy at 8 years of age revealed giant axonal neuropathy. The patient became increasingly demented and was incapacitated by weakness and ataxia; he died at 18 years of age. Histological examination of the brain and spinal cord showed numerous Rosenthal fibers, a distal axonopathy that most severely affected the corticospinal tracts, middle cerebellar peduncles, and posterior columns, and olivocerebellar degeneration.
Mendelian etiologies of stroke
Authors: Natowicz Marchvin , Kelley Richard I.
Published: January 2005

There are many genetic disorders associated with an increased risk for stroke that may easily be overlooked in the valuation of both adult and pediatric acute stroke victims. The recognition of a genetic disorder as the cause of a stroke has important implications not only for the immediate care of the stroke victim, but often also for others in the patient's family who may be at risk for the same disease and for whom preventive measures sometimes can be taken. We present here a comprehensive review of genetic disorders associated with stroke in the nongeriatric age groups for which a causative role in the evolution of stroke has been recognized or is likely. For each disorder, the major clinical and biochemical characteristics as well as the probable pathogenetic mechanisms of stroke are discussed, together with the appropriate testing required to screen for and confirm the diagnosis. The great variety of genetic disorders and mechanisms causing stroke underscores the increasing importance of understanding genetic disease for appropriate diagnosis and treatment of a common clinical problem affecting both children and adults.
Cholinesterases within neurofibrillary tangles related to age and Alzheimer's disease
Authors: Mesulam M‐Marsel , Asuncion Morán M.
Published: January 2005

Enzyme histochemistry showed that a substantial number of cortical neurofibrillary tangles contain acetylcholinesterase and butyrylcholinesterase activities in patients with Alzheimer's disease and in nondemented aged individuals. In some areas of the brain, tangles containing each of these two enzymes were differentially distributed. In other areas, there was a very close overlap between the two types of cholinesterase.
Brain choline acetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy
Authors: Kish Stephen J. , Currier Robert D. , Schut Lawrence , Perry Thomas L. , Morito Caryl L.
Published: January 2005

We measured the activity of choline acetyltransferase, the cholinergic marker enzyme, in the brains of 17 patients from five established pedigrees with dominantly inherited olivopontocerebellar atrophy (OPCA). OPCA is a group of cerebellar ataxia disorders in which serious intellectual impairment is not typically considered to be an accompanying feature. Patients from all five pedigrees demonstrated markedly reduced choline acetyltransferase activity in the cerebral cortex, with less severe changes in the hippocampus. Although the magnitude of the cortical choline acetyltransferase deficit is comparable to that seen in the brains of patients with Alzheimer's disease, none of our OPCA patients appeared, on last examination, to have severe global dementia of the Alzheimer type. Determination of the clinical significance of our biochemical data must await the results of studies in which the cognitive status of OPCA individuals has been accurately assessed.
Transplantation in Parkinson's disease: Two cases of adrenal medullary grafts to the putamen
Authors: Lindvall Olle , Backlund Erik‐Olof , Farde Lars , Sedvall Göran , Freedman Robert , Hoffer Barry , Nobin Anders , Seiger ÅKe , Olson Lars
Published: January 2005

Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two‐day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine‐rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.
Motor fluctuations in Parkinson's disease: Pathogenetic and therapeutic studies
Authors: Mouradian M. M. , Juncos J. L. , Fabbrini G. , Chase T. N.
Published: January 2005

The response to continuous intravenous infusion of levodopa was evaluated in 23 patients with Parkinson's disease complicated by motor fluctuations. Conversion from oral to intravenous levodopa treatment resulted in an immediate and sustained stabilization of plasma levodopa levels in both the wearing‐off and on‐off groups. Motor variability also diminished within the first 24 hours of infusion, although to a much greater extent in patients with the wearing‐off phenomenon. Over the next 5 to 11 days of intravenous treatment, further reductions in motor fluctuations occurred in both groups, at a substantially faster rate in the wearing‐off group than in the on‐off group. The degree of immediate stabilization of parkinsonian motor response correlated best with disease duration, whereas the rate of subsequent improvement correlated most closely with levodopa dose. The results support the view that the wearing‐off phenomenon may reflect the degeneration of dopamine terminals as a consequence of natural disease progression with a resultant inability to buffer variations in levodopa availability; the on‐off phenomenon may reflect additional postsynaptic changes, possibly occurring in response to the nonphysiological fluctuations in synaptic dopamine, which gradually remit during continuous levodopa administration.
Magnetic resonance imaging in multiple sclerosis: Decreased signal in thalamus and putamen
Authors: Drayer Burton P. , Burger Peter , Hurwitz Barrie , Dawson Deborah , Cain John , Leong Jackie , Herfkens Robert , Allan Johnson G.
Published: January 2005

High‐field strength (1.5 Tesla) magnetic resonance imaging in 15 patients with multiple and extensive white‐matter lesions and clinically definite multiple sclerosis delineated a previously underscribed finding of abnormally Decemberreased signal intensity on T2‐weighted images in the thalamus and putamen. The Decemberreased signal intensity (preferential Decemberreased T2 relaxation time) is most likely to be related to abnormally increased iron accumulation causing local magnetic field heterogeneities.
Abnormal glutamate metabolism in amyotrophic lateral sclerosis
Authors: Plaitakis Andreas , Caroscio James T.
Published: January 2005

Glutamate levels were determined in the fasting plasma of 22 patients with early‐stage primary amyotrophic lateral sclerosis (ALS) and compared to those of healthy and diseased controls. There was a significant increase (by approximately 100%, p < 0.0005) in the plasma glutamate of the ALS patients as compared with the controls. Oral glutamate loading (60 mg of monosodium glutamate per kilogram of body weight, taken orally after overnight fasting) resulted in significantly greater elevations in the plasma glutamate and aspartate levels in the ALS patients than in the controls. Glutamate, a potentially neuroexcitotoxic compound, is thought to be the transmitter of the corticospinal tracts and certain spinal cord interneurons. A systemic defect in the metabolism of this amino acid may underlie primary ALS.
The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis
Authors: Whitaker John N.
Published: January 2005

A polyclonal antiserum has been produced that can detect nanogram amounts of myelin basic protein (MBP)–like material in unconcentrated human urine. The urinary immunoreactive material is cross‐reactive with human MBP peptides 45–89 and 69–89, dialyzable, heat resistant, and is not an artifact of either degradation of radioligand or salt effect. An octapeptide, MBP peptide 82–89, was demonstrated to be the smallest peptide containing the main epitope against which this antiserum was directed. This epitope differed from the major epitope recognized by antisera detecting MBP‐like material in cerebrospinal fluid, implying that the MBP‐like material is altered, presumably degraded, in the kidney. Results of gel filtration and high‐performance liquid chromatography suggested a size of 1,000 daltons or less and a charge similar to that of human MBP peptide 80–89. In a group of 39 persons with multiple sclerosis, 48 with other neurological diseases, and 26 normal control subjects, the concentration of urinary MBP‐like material, related to the concentration of urinary creatinine, was significantly higher in the multiple sclerosis group (22.0 ng MBP‐like material/mg creatinine) than in the other neurological diseases or control groups, in which the values were 7.0 and 3.9 ng MBP‐like material/mg creatinine, respectively. Variations in the level of MBP‐like material appearing in the urine may provide a clinically feasible test for myelin damage. The precise identification of the chemical nature of the urinary MBP‐like material may also furnish a means for further analyzing the in vivo catabolism of the potentially autoantigenic MBP.
Magnetic brain stimulation: Central motor conduction studies in multiple sclerosis
Authors: Hess Christian W. , Mills Kerry R. , Murray Nicholas M. F. , Schriefer Thomas N.
Published: January 2005

Central motor conduction (CMC) was evaluated in 32 normal subjects and 83 patients with multiple sclerosis, and the findings were correlated with clinical signs and evoked potential data. CMC time was obtained from the latency difference in responses from the abductor muscle of the little finger to magnetic stimulation of the motor cortex and electrical stimulation at the C‐7/T‐1 interspace. Mean CMC time in normal subjects was 6.2 msec (SD 0.86 msec), and amplitudes of responses to cortical stimuli were at least 18% of those obtained with stimuli at the wrist. CMC was abnormal in 60 patients with multiple sclerosis (72%); this correlated well with brisk finger flexor jerks (p < 0.005). CMC was abnormal in 79% of patients with weakness of the abductor muscle of the little finger and in 54% with a normal muscle. Neurological examination was normal in 7 arms with abnormal CMC. Visual evoked potentials were abnormal in 67%, somatosensory evoked potentials in 59%, and brainstem auditory evoked potentials in 39% of those tested. For each procedure more subjects had abnormal CMC and normal evoked potentials than the reverse. The technique is of value for demonstrating and documenting central motor pathway lesions in multiple sclerosis, especially when physical signs are equivocal.
Dystonia in parkinson's disease: Clinical and pharmacological features
Authors: Poewe W. H. , Lees A. J. , Stern G. M.
Published: January 2005

We studied the features of dystonia in 9 patients with untreated idiopathic Parkinson's disease and in 56 patients on sustained treatment with L‐dopa. Dystonia was seen as an initial symptom in patients with both early‐ and late‐onset Parkinson's disease and included action dystonia of the limbs and cranial dystonia. Although the coexistence of parkinsonism and dystonia suggests a common pathophysiology, antiparkinsonian drugs did not consistently influence dystonic spasms. L‐dopa‐induced dystonia was seen as an off‐period, biphasic, or peak‐dose phenomenon. Each type showed a distinctive pattern of localization of dystonic spasms, possibly reflecting neurochemical aspects of basal ganglia somatotopy. Neuropharmacological studies performed in 12 patients suggest that off‐period dystonia is genuinely induced by L‐dopa and best relieved by antiparkinsonian agents.
Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques
Authors: Katzman Robert , Terry Robert , DeTeresa Richard , Brown Theodore , Davies Peter , Fuld Paula , Renbing Xiong , Peck Arthur
Published: January 2005

Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy‐eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age‐matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (> 90μm2 in a cross‐sectional area in cerebral cortex) as compared to age‐matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.
Motor unit synchronization in physiologic, enhanced physiologic, and voluntary tremor in man
Authors: Logigian Eric L. , Wierzbicka Margaret M. , Bruyninckx Francis , Wiegner Allen W. , Shahahi Bhagwan T. , Young Robert R.
Published: January 2005

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta‐adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion‐extension movements mimicking tremor (VT). Cross‐correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recording during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster‐firing motor units that had burst repetition rates in the range of slower‐firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.
A new model of embolic stroke produced by photochemical injury to the carotid artery in the rat
Authors: Futrell Nancy , Watson Brant D. , Dietrich W. Dalton , Prado Ricardo , Millikan Clark , Ginsberg Myron D.
Published: January 2005

We report a new model of embolic stroke in the rat, based on endothelial disruption and platelet aggregation in the carotid artery, which leads to distal embolization and focal brain infarction. The common carotid artery was irradiated for 6.5 minutes with the focused beam of an argon laser operated at a wavelength of 514.5 nm with a peak power of 2 W and an average power of 400 mw. Ipsilateral cerebral infarcts, ranging in size from 0.1 to 1.7 mm, were produced by platelet emboli in 12 of 13 rats. A total of 44 infarcts were observed in the 12 rats: 29 in the cortex, 6 in the hippocampus, 5 in the thalamus, and 4 in the basal ganglia. Scanning electron microscopy identified platelet aggregates in the carotid artery and in a deep cortical arteriole 50 minutes after the photochemical lesion. Twenty‐four hours after the experiment, scanning electron microscopy of the carotid artery revealed damaged endothelium but few remaining adherent platelets. More intense laser irradiation in 8 rats, leading to carotid occlusion, produced an infarct in only 1. This new model can be used to study the acute and chronic pathological changes in the brain associated with platelet embolism.
Cerebrospinal fluid antibodies to myelin basic protein in acute idiopathic optic neuritis
Authors: Warren Kenneth G. , Catz Ingrid , Bauer Christopher
Published: January 2005

Free and bound levels of anti‐myelin basic protein (anti‐MBP) antibodies were measured by radioimmunoassay in the cerebrospinal fluid of 20 patients with acute idiopathic optic neuritis, 133 patients with multiple sclerosis (MS) divided into three clinical subgroups, and 76 normal control subjects. Patients with idiopathic optic neuritis had elevated levels of anti‐MBP predominantly in free form, resulting in an elevated (above unity) free/bound anti‐MBP ratio similar to that of MS patients with acute relapses. These data suggest that acute idiopathic optic neuritis, like active MS, is associated with anti‐MBP.
The role of macrophages in experimental autoimmune neuritis induced by a P2‐Specific T‐Cell line
Authors: Heininger Kurt , Schäfer Bärbel , Hartung Hans‐Peter , Fierz Walter , Linington Christopher , Toyka Klaus V.
Published: January 2005

A P2‐specific T‐cell line with a helper/inducer phenotype (W3/25+) mediates experimental autoimmune neuritis in the Lewis rat after adoptive transfer to naive recipients. Moderately severe disease was induced in these experiments by the injection of 1 × 107 T cells. Motor and mixed afferent nerve conduction, F responses, H reflexes, and lumbar somatosensory evoked potentials were monitored, and morphological alterations were scored semiquantitatively at the end of the experiments. The role of macrophages and macrophage‐derived inflammatory mediators in the effector phase of the disease was investigated by administering different inhibitors of macrophage metabolism, including silica, dexamethasone, and a variety of cyclooxygenase and lipoxygenase blockers. Silica and dexamethasone suppressed the clinical, electrophysiological, and morphological manifestations of the disease almost completely, indicating that macrophages are essential for the generation of inflammatory lesions. The inhibitors of arachidonic acid conversion failed to mitigate the severity of the disease. This is in contrast to observations in actively induced experimental autoimmune neuritis in which eicosanoid biosynthesis seems to play a decisive role in the pathogenesis of the disease.
Central pontine myelinolysis after rapid correction of hyponatremia: A magnetic resonance imaging study
Authors: Brunner John E. , Redmond Janice M. , Haggar Allan M. , Elias Stanton B.
Published: January 2005

We describe a patient with severe hyponatremia (serum sodium 94 mmol/L) who developed encephalopathy and decorticate posturing after a 29 mmol/L rise in serum sodium concentration during the first 24 hours of correction. High‐resolution computed tomography of the pons was normal during the first, second, and twelfth weeks of the illness. Subsequent magnetic resonance imaging revealed a pontine lesion consistent with central pontine myelinolysis.
Inflammatory myelinoclastic diffuse sclerosis
Authors: Mehler Mark F. , Rabinowich Lydia
Published: January 2005

We report on a 12‐year‐old girl with a severe subacute to chronic bifrontal leukoencephalopathy. By clinical, biochemical, radiological, and neuropathological criteria, a diagnosis of inflammatory myelinoclastic diffuse sclerosis was reached. This is the third fully documented case.
Magnetic resonance imaging in amyotrophic lateral sclerosis
Authors: Goodin Douglas S. , Rowley Howard A. , Olney Richard K.
Published: January 2005

Magnetic resonance imaging (MRI) was used in 5 patients with clinically definite amyotrophic lateral sclerosis to determine the frequency of central white matter abnormalities. Two patients had symmetrical areas of increased signal intensity seen on MRI extending from the cortex, through the corona radiata, posterior limb of the internal capsule, and cerebral peduncles into the pons. These MRI abnormalities presumably relate to the pathological changes observed by others in the central white matter of patients with amyotrophic lateral sclerosis.
Diagnostic criteria for rett syndrome
Authors:   The Rett Syndrome Diagnostic Criteria Work Group
Published: January 2005

Diagnostic criteria for Rett syndrome (RS) were developed by representatives of the International Rett Syndrome Association and the Centers for Disease Control for use in future clinical and epidemiological studies. Necessary criteria are: normal prenatal and perinatal period; normal psychomotor development through the first 6 months of life; normal head circumference at birth, with subsequent deceleration of head growth; loss of purposeful hand skills; severely impaired expressive and receptive language; apparent severe mental retardation; and gait apraxia and truncal apraxia/ataxia. Supportive criteria include breathing dysfunction, seizures, spasticity, scoliosis, and growth retardation. The diagnosis of RS in considered tentative until 2 to 5 years of age. The differential diagnosis includes other disorders associated with mental retardation, cerebral palsy, and seizure disorders. These diagnostic criteria for RS should foster reliable communication among investigators and enhance the epidemiological and clinical research of this important disorder.
Duodenal and gastric delivery of levodopa in parkinsonism
Authors: Kurlan Roger , Nutt John G. , Woodward William R. , Rothfield Kenneth , Lichter David , Miller Charlyne , Carter Julie H. , Shoulson Ira
Published: January 2005

To clarify the influence of gastric emptying on levodopa‐related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled‐release Sinemet (CR‐4). The rank order from greatest to least for both percentage of time “on” and average mobility score was CDI, CGI, ID, CR‐4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR‐4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR‐4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous‐release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.
Validation of clinical diagnostic criteria for Alzheimer's disease
Authors: Morris John C. , McKeel Daniel W. , Fulling Keith , Torack Richard M. , Berg Leonard
Published: January 2005

Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was the priMarchy dementing illness. Seventeen of the 26 SDAT subjects had been diagnosed when only mildly demented. Two control subjects were examined neuropathologically; AD was absent in both. We conclude that research clinical diagnostic criteria for SDAT, even in its mild stage, are valid.
Neurological basis of respiratory complications in achondroplasia
Authors: Nelson F. William , Hecht Jacqueline T. , Horton William A. , Butler Ian J. , Goldie William D. , Miner Michael
Published: January 2005

Evaluation of 32 individuals with achondroplasia revealed that 28% had a history of apnea and 22% had respiratory abnormalities on polysomnography. In those patients requiring posterior fossa Decemberompressive surgery, improvement was noted in follow‐up polysomnograms. Multimodality studies suggested that brainstem compression was common in achondroplasia and could account in part for the abnormal respiratory function in this disorder, including obstructive apnea, central apnea, and hypoxemia.
Prediction of intracerebral hemorrhage survival
Authors: Tuhrim Stanley , Dambrosia James M. , Price Thomas R. , Mohr Jay P. , Wolf Philip A. , Heyman Albert , Kase Carlos S.
Published: January 2005

The Pilot Stroke Data Bank obtained information on 94 patients with intracerebral hemorrhage. These data were used to identify factors predictive of 30‐day outcome from among 85 demographic, historical, clinical, and laboratory variables generally available to clinicians on the day of admission. The 9 univariate factors statistically associated with outcome were Glasgow Coma Scale score, systolic blood pressure, pulse pressure, horizontal and vertical gaze palsies, severity of weakness, presence of brainstem‐cerebellar deficits, interval stroke course, and parenchymal hemorrhage size. Beginning with these factors, a step‐down variable selection procedure was used to derive a logistic regression model, containing only Glasgow Coma Scale score, pulse pressure, and hemorrhage size, that could be used to categorize correctly 92% of the patients as alive or dead at 30 days after onset.
Activated t‐lymphocytes with polyclonal gammopathy in patients with human t‐lymphotropic virus type i—associated myelopathy
Authors: Mori Masataka , Kinoshita Kenichiro , Ban Nobutaro , Yamada Yasuaki , Shiku Hiroshi
Published: January 2005

Human T‐lymphotropic virus type I (HTLV‐1)‐associated myelopathy (HAM) has been shown to be closely related to HTLV‐I infection. However, the mechanism by which this disease occurs after infection with HTLV‐I is still obscure. We found that HAM patients have unusually high proportions of CD4+HLADR+ cells, CD8+HLA‐DR+ cells, OKT9+ cells, and CD38(0KTlO)+ cells in their peripheral blood, all of which suggest the presence of activated T‐lymphocytes. Antibody titer against HTLV‐I was much higher in HAM patients than in HTLV‐I carriers without evident neurological disease (p < 0.01). Polyclonal gammopathy was also observed in most HAM patients, and 6 of 10 patients were positive for rheumatoid factor. These observations, coupled with the previous observation that corticosteroid therapy improves clinical symptoms in some patients, make it likely that continuous activation of the immune system, initiated by HTLV‐I infection, plays a key role in the pathogenesis of HAM.
The corpus callosum is larger with right‐hemisphere cerebral speech dominance
Authors: O'Kusky John , Strauss Esther , Kosaka Brenda , Wada Juhn , Li David , Druhan Marchgaret , Petrie Julie
Published: January 2005

Variations in the size of the human corpus callosum were examined as a possible morphological substrate of functional asymmetries of the cerebral hemispheres, such as cerebral speech dominance. The midsagittal surface area of the corpus callosum, obtained by magnetic resonance imaging, was measured in 50 patients with epilepsy and 50 neurologically normal control subjects. The mean callosal area did not differ significantly between patients and control subjects, between left‐handed and right‐handed subjects, or between men and women. When measurements were compared among 44 patients, whose cerebral speech dominance had been determined by the intracarotid injection of sodium amytal, the area of the corpus callosum was significantly greater in patients with right‐hemisphere cerebral speech dominance. The mean callosal area was greater by 109 to 159 square millimeters (18–28%) when compared to that of patients with either left‐hemisphere speech dominance or bilateral speech representation. This difference in midsagital surface area could represent as many as 37 to 54 million additional callosal axons in subjects with right‐hemisphere celebral speech dominance.
Alz 50 recognizes abnormal filaments in Alzheimer's disease and progressive supranuclear palsy
Authors: Tabatonm Massimo , Whitehouse Peter J. , Perry George , Davies Peter , Autilio‐Gambetti Lucila , Gambetti Pierluigi
Published: January 2005

The monoclonal antibody Alz 50 recognizes a 68‐kDa protein present in large amounts in cerebral tissue of patients with Alzheimer's disease (AD). We used light and electron microscopic as well as quantitative immunochemical techniques to compare distribution, characteristics, and amount of Alz 50 antigen in the tegmental nuclei of the pons of subjects with progressive supranuclear palsy (PSP) and subjects with AD. In both condtions Alz 50 antigen was found in neurons with and without neurofibrillary tangles (NFT). In NFT‐bearing neurons the antigen was located in the filamentous components of NFT in both diseases, i.e., in straight filaments forming the NFT in PSP and in paired helical filaments components of the NFT in AD. In neurons lacking NFT the antigen was associated with straight filaments of various sizes, but the straight filaments were generally thinner than those of PSP. On immunoblots of both PSP and AD tissues, Alz 50 recognized a set of bands between 68 and 35 kDa which were not present in control tissue. The amount of Alz 50 antigen in AD tissue was estimated to be 10 times higher than that present in PSP tissue. The higher amount of Alz 50 ancigen in AD tissue correlates with the more severe fibrillary pathology in this disease than in PSP. We propose that the Alz 50 antigen, although possibly related to tau proteins, distinguishes neurons that are forming abnormal filaments.
Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease
Authors: Burke William J. , Chung Hyung D. , Huang Jung S. , Huang Shuan S. , Haring John H. , Strong Randy , Marchshall Gary L. , Joh Tong H.
Published: January 2005

Alzheimer's disease (AD) is associated with a progressive loss of locus ceruleus neurons. These noradrenergic neurons receive a major afferent projection from epinephrine neurons in epinephrine cell groups in the brainstem. The epinephrine neurons have a specific enzymatic Marchker, phenylethanolamine N‐methyltransferase (PNMT), which allows them to be identified chemically and immunohistochemically. We have previously reported a Decemberrease in PNMT in brains of patients with AD. We now report that the Decemberrease in PNMT activity in projections to the locus ceruleus is not due to the loss of epinephrine neurons, although up to 33% of these neurons are atrophic. The Decemberrease in presynaptic PNMT does, however, correlate with the loss of postsynaptic locus ceruleus neurons in brains from AD patients. The percentage of degenerating neurons in the epinephrine nuclei also correlates significantly with the amount of loss of locus ceruleus neurons in AD. In addition, there is a 55% Decemberrease in mitogen activity, a nonspecific measure of growth or maintenance factors, in dialysed locus ceruleus extracts from the AD patients compared to those from control subjects. The mitogen activity in the locus ceruleus was significantly correlated with PNMT activity and with the density of locus ceruleus neurons in all cases examined. These findings provide evidence for the hypothesis that retrograde degeneration is a mechanism of neuronal degeneration in AD and suggest that trophic factors may play a role in this process.
Immunohistochemical verification of senile and kuru plaques in Creutzfeldt‐Jakob disease and the allied disease
Authors: Kitamoto Tetsuyuki , Tateishi June , Sato Yuji
Published: January 2005

We investigated paraffin‐embedded brain sections from 41 patients with Creutzfeldt‐Jakob disease (CJD) and from 9 with Gerstmann‐Sträussler syndrome (GSS) using anti—human prion protein (PrP) antisera (anti—GSS kuru plaque cores and anti—PrP synthetic peptide) and anti—β protein antiserum. The anti—human PrP antiserum reacted with the plaques in CJD and GSS, with or without degenerative neurites (neuritic components). In addition, the anti—β protein antiserum immunolabeled kuru plaque—like compact plaques in some cases of CJD. Therefore, previous morphological classifications of the plaques may not always be valid. Senile plaques labeled with anti—β protein antiserum were evident in 65% of the CJD brains and 50% of GSS brains from patients in their 60s, and in 73% of brains from CJD patients in their 70s, but not in brains from patients under 60 years of age. The incidence of the senile plaques was compatible with the normal aging process and was apparently not accelerated by the disease process of CJD or GSS. These immunostaining approaches using anti—human PrP and anti—β protein antisera allow classification of plaque types and increase the reliability of the pathological diagnosis in persons with dementia.
Rate of cell death in parkinsonism indicates active neuropathological process
Authors: McGeer Patrick L. , Itagaki Shigeru , Akiyama Haruhiko , McGeer Edith G.
Published: January 2005

It has been hypothesized that idiopathic parkinsonism might be due to age‐related attrition of dopamine neurons occurring long after an initial acute episode. We present evidence against this hypothesis, based on our finding of at least six times as many HLA‐DR—positive microglia phagocytosing dopamine neurons in parkinsonian brains as in control brains. This difference indicates an active pathological process.
Hypertrophic brachial plexus neuritis: A pathological study of two cases
Authors: Cusimano Michael D. , Bilbao Juan M. , Cohen Sandra M.
Published: January 2005

Two patients with brachial plexus neuropathy had recurrent symptoms for years that culminated in the development of a Painful lower cervical mass. On macroscopic examination the affected nerves had a fusiform segmental enlargement, suggestive of a nerve sheath tumor, that was excised. Histologically, Marchked endoneurial edema, florid focal chronic inflammation, extensive onion bulb formation, and perineurial sparing were seen. Electron microscopic studies on one patient revealed microvasculitis; frequent tubuloreticular inclusions in endothelial cells, histiocytes, and lymphocytes; and cylindrical confronting cisternae in lymphocytes. We conclude that some cases of recurrent brachial plexus neuropathy are due to a localized chronic inflammation that may be related to autoimmunity or to a viral infection.