bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities of the nucleus basalis in Down's syndrome
Authors: Casanova Manuel F. , Walker Lary C. , Whitehouse Peter J. , Price Donald L.
Published: January 2005

One of the most striking manifestations of Down's syndrome is profound mental retardation. Furthermore, after 35 years of age, many patients with Down's syndrome develop clinical and pathological features of Alzheimer's disease. Since brains of patients with Alzheimer's disease show significant loss of neurons in the nucleus basalis of Meynert (nbM), we sought to establish normal standards of nbM neurons in persons with Down's syndrome and to determine whether reductions in the number of neurons occur with increasing age. The number and size of neurons in the nbM were measured in selected sagittal sections from 5 patients with Down's syndrome and 5 age‐matched controls. The patients (age range, 16 to 56 years) had 29% fewer nbM neurons than controls, and the oldest patient had the lowest cell count of all subjects. The size of nbM neurons did not differ significantly between the two groups. Our results show that the nbM contains fewer neurons in young persons with Down's syndrome than in normal controls and suggest that the number of these nerve cells may be further reduced in older persons with Down's syndrome.
Cerebral infarction in sickle cell trait
Authors: Greenberg Joel , Massey E. Wayne
Published: January 2005

Sickle cell disease is known to predispose patients to the risk of cerebral infarction. However, only scattered reports exist of the neurological sequelae of the sickle cell trait. Only 8 cases are reported in the English literature, in some of which the sickle cell trait was not documented by hemoglobin electrophoresis. This report describes 2 men, age 35 and 24 years, who developed acute cerebral infarction. Investigation revealed no apparent cause for the lesion other than the sickle cell trait.
Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: Correlation with neuropathology
Authors: Ginsberg Myron D. , Graham David I. , Busto Raul
Published: January 2005

Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high‐grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double‐tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in “selectively vulnerable” areas of the forebrain.
Hallervorden‐Spatz disease: Cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus
Authors: Perry Thomas L , Norman Margaret G. , Yong Voon Wee , Whiting Sharon , Crichton John U. , Hansen Shirley , Kish Stephen J.
Published: January 2005

We describe neurochemical abnormalities found in the brains of 2 patients with autopsy‐confirmed Hallervorden‐Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione‐cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. γ‐Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden‐Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden‐Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.
Progressive multifocal leukoencephalopathy: Investigation of three cases using in situ hybridization with JC virus biotinylated DNA probe
Authors: Aksamit Allen J. , Mourrain Pascale , Sever John L , Major Eugene O.
Published: January 2005

Using the technique of in situ DNA‐to‐DNA hybridization, a JC virus biotinylated DNA probe was developed and applied to formalin‐fixed, paraffin‐embedded, or fixed, frozen sections of brain tissue from three subjects with progressive multifocal leukoencephalopathy (PML). Light microscopy was carried out to correlate the presence of JC virus DNA with the selective infection of oligodendrocytes and astrocytes in PML. Oligodendrocytes (lytically infected) showed the greatest evidence of viral DNA. More astrocytes showing bizarre morphological changes had evidence of viral DNA than did astrocytes that were simply reactive. Viral DNA was not evident in vascular endothelial cells using this technique. Viral DNA replication may be an important initial step which produces the bizarre “transformed” astrocytes of PML. Findings in this study do not support the hypothesis that vascular endothelial replication is important in the pathogenesis of JC virus–induced PML. In situ hybridization with biotinylated JC virus probe may be useful in the diagnosis of PML on brain biopsy specimens.
Treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid
Authors: Pedley Timothy A. , Emerson Ronald G. , Warner Carolyn L. , Rowland Lewis P. , Salen Gerald
Published: January 2005

We describe a patient with cerebrotendinous xanthomatosis who was treated for one year with chenodeoxycholic acid. Modest clinical improvement was accompanied by marked improvement in visual and brainstem auditory evoked potentials. Improved central nervous system function coincided with return of plasma and cerebrospinal fluid cholestanol levels to normal.
Dopaminergic and cholinergic lesions in progressive supranuclear palsy
Authors: Ruberg Merle , Javoy‐Agid France , Hirsch Etienne , Scatton Bernard , Lheureux Rémy , Hauw Jean‐Jacques , Duyckaerts Charles , Gray Françloise , Morel‐Maroger Ariel , Rascol André , Serdaru Michel , Agid Yves
Published: January 2005

In 9 patients with progressive supranuclear palsy and in 27 controls, dopamine and homovanillic acid concentrations, choline acetyltransferase (CAT) activity, and the number of [3H]spiperone and [3H]quinuclidinyl benzilate binding sites were measured post mortem in the striatum (caudate nucleus, putamen, and nucleus accumbens), substantia innominata, and frontal cortex. Dopamine and homovanillic acid concentrations were reduced in the caudate nucleus and putamen but not in the nucleus accumbens or frontal cortex, indicating that the nigrostriatal dopaminergic system is lesioned in patients with progressive supranuclear palsy (as in those with Parkinson's disease) but not the mesocortical and mesolimbic dopaminergic systems, which are lesioned in parkinsonian patients. CAT activity and [3H]spiperone binding decreased in parallel fashion in all the structures. In the striatum, this suggests that the cholinergic neurons, which are target cells of the nigrostriatal system, also degenerate in this disease. This might explain the decrease in the number of dopamine receptors as well as the inefficacy of levodopa or anticholinergic therapy in these patients. The decrease in CAT activity in the substantia innominata and the frontal cortex indicates that the innominatocortical cholinergic system is lesioned in patients with progressive supranuclear palsy and may play a role in the intellectual deterioration observed. This lesion is also found in demented patients with Alzheimer's and Parkinson's diseases.
Progressive supranuclear palsy: Relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers
Authors: Kish S. J. , Chang L. J. , Mirchandani L , Shannak K. , Hornykiewicz O.
Published: January 2005

Biochemical markers for the major neurotransmitter systems were measured in the brains of 5 patients who had died with neuropathologically confirmed progressive supranuclear palsy. A marked nigrostriatal dopamine deficiency, observed in 4 of the 5 patients, was sufficient to explain the parkinsonian features (especially bradykinesia) observed in patients with progressive supranuclear palsy. Dopamine concentrations, however, were normal in the nucleus accumbens, hypothalamus, and temporal cortex. Brain noradrenalin, serotonin, γ‐aminobutyric acid, and aspartic acid levels were generally normal. Normal brain choline acetyltransferase activity (the marker enzyme for cholinergic neurons) in the 2 patients with severe dementia suggests that, at least in some patients, the cognitive impairment in this disorder is likely to be related to noncholinergic neurotransmitter system changes. The glutamic acid concentration was elevated in many brain areas in 3 of the 5 patients studied.
Nonepileptogenic epileptiform electroencephalographic activity
Authors: Klass Donald W. , Westmoreland Barbara F.
Published: January 2005

Accumulated experience has delineated numerous distinctive electroencephalographic (EEG) patterns that are morphologically epileptiform but have no relationship to the process responsible for generating epileptic seizures and have little or no practical value for diagnosis. These anomalous patterns need to be distinguished carefully from the highly abnormal types of EEG activity that continue to have important diagnostic value.
Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosyl groups
Authors: Ilyas Amjad A. , Quarles Richard H. , Dalakas Marinos C. , Fishman Peter H. , Brady Roscoe O.
Published: January 2005

Monoclonal IgM K from a patient with polyneuropathy associated with paraproteinemia was found to bind to several polysialogangliosides. Binding of IgM to gangliosides was shown by enzyme‐linked immunosorbent assay (ELISA) and by overlaying thin‐layer chromatograms of human brain and peripheral nerve gangliosides with the patient's serum followed by radioiodinated goat antihuman IgM. The latter technique showed that the IgM paraprotein reacted with a number of gangliosides. In an ELISA the IgM paraprotein reacted strongly with GD2, GD3, GD1b, and GT1b, but not with GM1, GM3, and GD1a. Thus, the epitope for the patient's IgM paraprotein appears to involve the disialosyl configurations.
Identification of the inflammatory cells in the central nervous system of patients with adrenoleukodystrophy
Authors: Griffin Diane E. , Moser Hugo W. , Mendoza Querubin , Moench Thomas R. , O'Toole Susan , Moser Ann B.
Published: January 2005

Adrenoleukodystrophy is a disorder of long‐chain fatty acid metabolism associated with adrenal cortical insufficiency and central nervous system demyelination. The central nervous system disease is unusual in that it is abrupt in onset and accompanied by a considerable infiltration of mononuclear inflammatory cells. To determine the nature of these inflammatory cells, immunocytochemical staining was carried out on the mononuclear cells in the brain and cerebrospinal fluid of patients with adrenoleukodystrophy. Monoclonal antibodies to T lymphocytes (T11), the helper/inducer (T4) and cytotoxic/suppressor (T8) subsets of T lymphocytes, B lymphocytes (B1), and monocyte/macrophages (Ml or esterase) were used. Mononuclear cells in the perivascular cuffs of autopsy material from 4 patients were, on average, 59% T cells, 34% T4 cells, 16% T8 cells, 24% B cells, and 11% monocyte/macrophages. Cerebrospinal fluid from 8 of 10 patients had increased IgG concentrations. Mononuclear cells in the cerebrospinal fluid of 6 patients with active disease were, on average, 61% T cells, 40% T4 cells, 16% T8 cells, 3% B cells, and 18% monocyte/macrophages. This distribution of cells is similar to that found in the central nervous system during a cellular immune response and suggests the possibility that one component of this disease is immunologically mediated.
Acute effects of antidepressants on hippocampal seizures
Authors: Clifford David B. , Rutherford James L. , Hicks Frederick G. , Zorumski Charles F.
Published: January 2005

Electrically kindled hippocampal seizures in rats were used to evaluate the acute effects of the antidepressants amitriptyline, imipramine, desipramine, bupropion, maprotiline, and trazodone on behavioral and electrical convulsions. All of the drugs reduced afterdischarge duration significantly. Behavioral seizures were not significantly reduced by bupropion or trazodone, whereas the other drugs did reduce seizure severity. Afterdischarge threshold was not modified by these drugs. In contrast, phenobarbital significantly elevated threshold and reduced seizure severity and afterdischarge duration. Amitriptyline was the most effective antidepressant, attenuating both seizure severity and afterdischarge duration.
Multiple sclerosis: Activated cells in cerebrospinal fluid in acute exacerbations
Authors: Noronha Avertano , Richman David P. , Arnason Barry G. W.
Published: January 2005

Cerebrospinal fluid (CSF) lymphocytes from three young patients undergoing acute exacerbations of multiple sclerosis were studied by flow cytometry. Using a new method that simultaneously measures cell‐surface antigens and the cell‐cycle phase, we determined that the CSF lymphocytes in these patients were activated. The majority of the activated cells expressed the OKT4 phenotype, while very few expressed the OKT8 phenotype.
Thrombotic cerebral vasculopathy associated with herpes zoster
Authors: Eidelberg David , Sotrel Ana , Horoupian D. S. , Neumann Paul E. , Pumarola‐Sune Tomas , Price Richard W.
Published: January 2005

We describe the clinical, radiographic, and pathological findings in 3 patients with large‐vessel cerebral vasculopathy following herpes zoster. Two of the patients were studied at postmortem examination, and a brain biopsy was performed in the third. Each of the 3 patients suffered thrombotic occlusions of large vessels without notable inflammatory or granulomatous changes following trigeminal or segmental herpes zoster infection. In the 2 autopsied patients, varicella‐zoster virus (VZV) antigens were detected by immunoperoxidase staining within the media of the affected cerebral arteries. Little or no inflammation was associated with the foci of the VZV antigens. These studies provide evidence that the vasculopathy following herpes zoster may result from direct VZV infection of the artery and the in situ thrombosis can develop within the infected vessels in the absence of clear inflammatory vasculitis.
Impaired slow axonal transport in wobbler mouse motor neuron disease
Authors: Mitsumoto Hiroshi , Gambetti Pierluigi
Published: January 2005

We studied slow axonal transport and morphometry of forelimb axons in wobbler mice and controls. In wobbler mice, the total radioactivity migrating with the slow transport was decreased by 50%. The velocity of transport also appeared to be reduced; 15 days following administration of a radioisotope, polypeptides migrating with slow component a of transport did not form a peak and remained mostly 2 mm from the spinal cord, while in controls slow component a was distributed as a peak which was located 4 mm from the cord. The ratios of the 68‐kDa neurofilament subunit to tubulin and actin were significantly decreased (p < 0.01 and p < 0.005, respectively). This finding is consistent with a preferential reduction of the radioactivity migrating with neurofilament proteins in wobbler mice. Moreover, both the size and number of myelinated axons were markedly diminished, but their length was not significantly different, indicating that dying‐back does not take place in axons of wobbler mice up to 12 mm from the spinal cord. The reduction in axonal transport may be due to the reduction in number and caliber of the axons and/or to reduced protein synthesis in cervical lower motor neurons; however, the abnormal distribution of the radioactive substance definitely results from impairment of the slow transport in the axons of the forelimb roots of wobbler mice. The transport impairment is not related to the presence of morphological changes in the perikaryon of wobbler mouse lower motor neurons, as it is much more widespread than would be expected if only altered neurons were involved. Whether the impairment of the slow transport is the primary pathogenetic event in wobbler mouse lower motor neuron disease, as well as in other animals and human motor neuron diseases, remains to be established.
Low CSF protein concentration in idiopathic pseudotumor cerebri
Authors: Chandra Vijay , Bellur Srinath N. , Anderson Robert J.
Published: January 2005

An inverse relationship between the cerebrospinal fluid (CSF) opening pressure and the corresponding protein value was found for patients with idiopathic pseudotumor cerebri who underwent their first lumbar puncture (LP) prior to the initiation of therapy. This relationship provides evidence for a pressure‐dependent bulk flow absorption for CSF and also suggests that patients with high CSF pressures will have low CSF protein concentration.
Neurological involvement in hemolytic‐uremic syndrome
Authors: Sheth Kumudchandra J. , Swick Herbert M. , Haworth Nancy
Published: January 2005

Of 44 children with hemolytic‐uremic syndrome seen at Milwaukee Children's Hospital, 15 (34%) had neurological involvement. This group contained 8 boys and 7 girls, with a mean age of 3 1/4 years. Twelve patients had seizures within 48 hours of admission. Seizures were associated with hypertension, fever, hyponatremia, or hypocalcemia. Other neurological symptoms included altered consciousness, behavioral changes, diplopia, and dizziness. Hemiparesis (4 patients), eye involvement (7 patients), decerebrate posturing (2 patients), and ataxia (1 patient) were present on physical examination. Cerebrospinal fluid examination showed increased protein in 4 of 11 patients. Electroencephalograms were abnormal in all 9 patients tested. Computed tomographic and radionuclide scans showed evidence of vascular abnormalities in 4 of the 14 patients studied. Complete neurological recovery occurred in only 6 of the 15 children, while the remaining 6 demonstrated residual hemiparesis, seizures, and cortical visual defect. In those children with neurological involvement, there was a higher incidence of residual hypertension (49% versus 11%), chronic renal damage (40% versus 3.5%), and death (28% versus 0%), suggesting that central nervous system involvement indicates severe hemolytic‐uremic syndrome.
Periodic leg movements of sleep (nocturnal myoclonus): An electrophysiological study
Authors: Wechsler Lawrence R. , Stakes John W. , Shahani Bhaghwan T. , Busis Neil A.
Published: January 2005

Six patients with periodic leg movements of sleep (PLMS) were studied electrophysiologically. All patients had normal results on routine nerve conduction studies and electromyography. In 5 patients the blink reflex consisted of three components, and in 1 patient it consisted of four components, with two components being normal. The second component of their blink reflex did not habituate. Other abnormalities included long‐latency responses in the extremities in 2 patients, release of H‐reflexes from flexor hallucis brevis muscle in 2 patients, and an Hmax/Mmax ratio of 98% in 2 patients. One patient's median nerve somatosensory‐evoked response had a markedly enlarged P22 wave. These electrophysiological abnormalities suggest a disorder of the central nervous system producing increased excitability of segmental reflexes. To produce increased excitability of both brainstem and spinal cord reflexes, the disorder must be operative at the pontine level or rostral to it. Since long‐latency components of blink reflexes occurred in all our patients, this may be a helpful diagnostic test when PLMS is suspected.
Signs of focal posterior cerebral abnormality in early subacute sclerosing panencephalitis
Authors: Begeer J. H. , Haaxma R. , Snoek J. W. , Boonstra S. , le Coultre R.
Published: January 2005

In 16 cases of subacute sclerosing panencephalitis (SSPE), praxis and visual spatial capacities were more impaired early in the disease than were language functions. Together with the electroencephalographic findings, this suggests that the early lesions in SSPE are more pronounced in the parietooccipital area than in the classic language areas. Other reports also support such a localization. Detection of the disease in its early phase when dressing apraxia and visual impairment predominate is important in conducting clinical trials of different therapeutic agents.
Cerebellar infarction: Comparison of computed tomography and magnetic resonance imaging
Authors: Simmons Zachary , Biller José , Adams Harold P. , Dunn Val , Jacoby Charles G.
Published: January 2005

We correlated clinical, computed tomographic (CT), and magnetic resonance imaging (MRI) findings in 14 patients with cerebellar infarctions. Before MRI, the diagnosis of cerebellar infarction was made in only 7 patients on the basis of clinical and CT evidence. Cerebellar infarction was bilateral in 3 patients and was associated with brainstem infarction in 6. Infarction occurred in the territory of the posterior inferior cerebellar artery (PICA) in 12 patients. The territory of the superior cerebellar artery (SCA) was involved in 1 patient, and 1 infarction encompassed the watershed between the PICA and the SCA. In patients with infarction of the PICA territory, the medial and intermediate hemispheric segments were most frequently involved. Involvement of the lateral hemispheric segment was infrequent and was independent of brainstem involvement. Because of its fine demonstration of anatomical detail, its lack of bony artifact, and its ability to visualize infarctions readily within the first 24 hours, MRI is an excellent method for demonstrating cerebellar infarction.
Intrathecal interferon in subacute sclerosing panencephalitis
Authors: Huttenlocher Peter R. , Picchietti Daniel L. , Roos Raymond P. , Cashman Neil R. , Horowitz Bernard , Horowitz Marilyn S.
Published: January 2005

Five patients with clinically advanced subacute sclerosing panencephalitis (SSPE) were given human leukocyte interferon (IFN) by the lumbar route, 1 million IU every other day for a total of 30 days. Intrathecal IFN produced a meningeal inflammatory reaction in all patients and was associated with transient hemiparesis in 1. It persisted in the cerebrospinal fluid at measurable levels for 48 hours after a single injection. Although improvement was temporally related to intrathecal IFN in 1 patient, it is not clear whether this was induced by IFN or a spontaneous remission. A randomized controlled trial would be necessary to evaluate IFN critically as a therapy for SSPE.
Effect of dexamethasone on blood‐brain barrier in the normal mouse
Authors: Hedley‐Whyte E. Tessa , Hsu Dora W.
Published: January 2005

Dexamethasone ameliorates cerebral edema, but its effect on normal blood‐brain barrier is unknown, as is the site of action. Sixteen normal mice were given dexamethasone, 3 mg/kg intramuscularly or 2 mg/kg intravenously. One to two hours later 10 mg of horseradish peroxidase (HRP) in 0.1 ml of saline was administered intravenously and allowed to circulate for 15 minutes. Brain slices were examined by light and electron microscopy. The number of HRP‐permeable arteriolar segments per brain was less in dexamethasone‐treated than in control mice (p < 0.001). In addition, the number of small HRP‐filled endothelial vesicles of capillaries and of HRP‐permeable and ‐impermeable arterial segments was less in dexamethasone‐treated mice than that for similar vessels in control mice (p < 0.005, p < 0.05, and p < 0.01, respectively). The total number of small vesicles and the number of larger HRP‐filled vesicles in arterioles was the same in treated and control mice. Dexamethasone therefore decreased the normal permeability of cerebral blood vessels to HRP. This decrease was accompanied by a decrease in the number of HRP‐containing small endothelial vesicles. These data suggest that dexamethasone influences cerebral edema by decreasing the permeability of the cerebral vasculature for macromolecules.
Monozygotic twins with Parkinson's disease
Authors: Koller William , O'Hara Robert , Nutt John , Young James , Rubino Frank
Published: January 2005

A pair of monozygotic twins concordant for Parkinson's disease are described. The issue of genetic factors in Parkinson's disease is discussed.
Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy
Authors: Dyck Peter James , Lais Alfred , Karnes Jeannine L. , O'Brien Peter , Rizza Robert
Published: January 2005

Pathological, morphometric, and teased fiber sutides of sural nerve from 36 diabetic patients with (n = 32) and without (n = 4) neuropathy and from 47 healthy subjects provide evidence that in diabetic polyneuropathy: (1) fiber loss is primary; (2) demyelination and remyelination with or without onion bulb formation are secondary; (3) remaining fibers, on average, have the same ratio of small to large fibers as in healthy individuals, but with a greatly increased variability; and (4) the spatial distribution of fiber loss is both diffuse and multifocal. Criteria developed during the study of experimental modles of ischemic neuropathy were exployed to assess whether ischemic nerve damage had occured in diabetic polyneuropathy. We conclude that there is increasing evidence that microvascular pathological abnormality and ischemia may be involved in the pathogenesis of human diabetic polyneuropathy. Cases with selective loss of small or large afferent fibers are probably extremes of a normal distribution and not different disorders.
Axonal transport in the motor neurons of rats with neuropathy induced by p‐bromophenylacetylurea
Authors: Nagata Hiroshi , Brimijoin Stephen
Published: January 2005

Axonal transport was studied in sciatic motor neurons of rats with neuropathy induced by p‐bromophenylacetylurea (BPAU) in dimethylsulfoxide solution. Control rats were treated with the vehicle alone. To label rapidly transported proteins, the rats received an injection of 35S‐methionine into the ventral horn of the spinal cord at the L1 vertebral level. Radiolabeled protein was collected at ligatures applied on the sciatic nerve at intervals thereafter. In animals with severe motor weakness owing to treatment with BPAU, 400 mg/kg, there was evidence of increased delivery of labeled protein into the axon during the early period after isotope injection, but reduced delivery later. A dose‐dependent decrease in the amount of labeled protein recirculated by retrograde axonal transport was also noted. A significant reduction in the amoutn of protein transported retrogradely was also detected during the latent subclinical phase of the neuropathy. The velocity of rapid anterograde transport, examined in unligated sciatic nerves, was unaffected by BPAU treatment. However, the lag time between precursor injection and the onset of transport was shorter in BPAU‐treated rats than in controls. This effect was not explainable on the basis of fluctuations in core body temperature. The results are consistent with the view that disturbances of rapid anterograde and retrograde transport play a role in the peripheral neurotoxicity of BPAU. Attention is directed to the possibility that the transport disturbances and the subsequent neuropathy are related to alterations in the processing of rapidly transported membrane‐limited organelles in the nerve cell bodies.
The human anti–myelin‐associated glycoprotein IgM system
Authors: Murray Norman , Page Nicole , Steck Andreas J.
Published: January 2005

Two mouse monoclonal antiidiotypic antibodies that react with human monoclonal IgM antibodies with specificity for myelin‐associated glycoprotein (MAG) have been used to study the immunological specificity of the reported cross‐reactions involving the anti‐MAG IgM. Both of the antiidiotypic antibodies are shown to react with the combining site of their respective idiotypic IgM and to inhibit the reaction between IgM and MAG. Using these antiidiotypic antibodies as “surrogate” antigen, we have demonstrated immune cross‐reactivity between MAG, a human peripheral nerve glycolipid, and a low‐molecular‐weight protein of human peripheral nerve myelin. In addition, we have used the two antiidiotypic antibodies to conduct a search for evidence of shared idiotypy among 34 different neuropathy‐associated paraproteins. Our results provide no evidence for a neuropathy‐associated idiotype, suggesting a degree of polymorphism in the human anti‐MAG IgM system.
Antimigraine drug interactions with 5‐hydroxytryptamine1A receptors
Authors: Hiner Bradley C. , Roth Heidi L. , Peroutka Stephen J.
Published: January 2005

The interactions of four antimigraine drugs with 5‐hydroxytryptamine1A and beta‐adrenergic receptors were analyzed in rat brain membranes. Methysergide, cyprohepatadine, (−)propranolol, and pizotifen display similar affinities (IC50 values, 83 to 280 nM) for 5‐hydroxytryptamine1A receptors labeled by [3H]8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin. Cyproheptadine, pizotifen, and methysergide are essentially inactive at beta‐adrenergic receptors labeled by [3H]dihydroal‐prenolol (IC50 values, 8,700 to 87,000 nM). By contrast, (−)propranolol is an extremely potent beta‐adrenergic agent (IC50, 3 nM). These data indicate that the 5‐hydroxytryptamine1A receptor is a common site of action for (−)propranolol and other antimigraine agents.
The AIDS dementia complex: I. Clinical features
Authors: Navia Bradford A. , Jordan Barry D. , Price Richard W.
Published: January 2005

Of 70 autopsied patients with the acquired immune deficiency syndrome (AIDS), 46 suffered progressive dementia that was frequently accompanied by motor and behavioral dysfunction. Impaired memory and concentration with psychomotor slowing represented the most common early presentation of this disorder, but in nearly one half of the patients either motor or behavioral changes predominated. Early motor deficits commonly included ataxia, leg weakness, tremor, and loss of fine‐motor coordination, while behavioral disturbances were manifested most commonly as apathy or withdrawal, but occasionally as a frank organic psychosis. The course of the disease was steadily progressive in most patients, and at times was punctuated by an abrupt acceleration. However, in 20% of patients a more protracted indolent course was observed. In the most advanced stage of this disease, patients exhibited a stereotyped picture of severe dementia, mutism, incontinence, paraplegia, and in some cases, myoclonus. The high incidence and unique clinical presentation of this AIDS dementia complex is consistent with the emerging concept that this complication is due to direct brain infection by the retrovirus that causes AIDS.
Chronic idiopathic ataxic neuropathy
Authors: Dalakas Marinos C.
Published: January 2005

Fifteen patients with chronic sensory ataxia caused by a large‐fiber sensory neuropathy were studied and followed up for a period of 17.4 years (range, 4 to 41). When first seen, they had distal paresthesias and sensory ataxia of slow onset and progression, areflexia, normal strength, and a profound loss of proprioceptive and kinesthetic sensation extending up to the most proximal joints. Needle electromyogram and motor‐nerve conduction velocity findings were normal in most of the patients and sensory potentials were absent in all. Nerve biopsy showed severe loss of the large myelinated fibers. Nine patients had a serum monoclonal or polyclonal gammopathy (3 with IgMκ, 1 with IgAκ, and 5 with a polyclonal increase of IgG, IgA, or IgM), and 8 had elevated cerebrospinal fluid γgM globulin levels in spite of low normal total cerebrospinal fluid protein levels. No circulating antibodies to ganglionic neurons were found. Therapy with immunosuppressants or plasmapheresis was unsuccessful. All patients are disabled and their conditions have continued to worsen without signs of malignancy or systemic illness during a mean follow‐up period of 17.4 years.

Chronic idiopathic ataxic neuropathy is a proprioceptive neuropathy, clinically indistinguishable from the one associated with carcinoma or pyridoxine abuse due to involvement of the dorsal root ganglia, and could represent a distinct form of an indolent, slowly progressive sensory neuronopathy (ganglionopathy). Although immunopathological mechanisms may play a role, especially in patients with an associated paraproteinemia, the resistance of such patients to therapy, the progressive course, and the resemblance of this disorder to other toxic neuronopathies associated with pyridoxine abuse or doxorubicin administration suggest a possible toxic etiopathogenesis.
N‐acetyl‐β‐hexosaminidase β locus defect and juvenile motor neuron disease: A case study
Authors: Cashman Neil R. , Antel Jack P. , Hancock Larry W. , Dawson Glyn , Horwitz Allen L. , Johnson William G. , Huttenlocher Peter R. , Wollmann Robert L.
Published: January 2005

A patient with partial deficiency of N‐acetyl‐ß‐hexosaminidase (Hex) developed a progressive motor neuron syndrome beginning at age 7, characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Minor clinical features have included tremor and late distal sensory abnormalities. Rectal biopsy at age 24 demonstrated membranous cytoplasmic bodies in submucosal ganglion cells. Biochemical evaluation revealed nearly absent Hex B activity in serum, leukocytes, and fibroblasts, with partial Hex A activity in serum and leukocytes, and low normal Hex A activity in fibroblasts. Motor neuron disease can be a presentation of a Hex ß locus defect, in addition to the previously recognized Hex α locus defects.
Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions
Authors: Hauser Stephen L. , Bhan Atul K. , Gilles Floyd , Kemp Maurice , Kerr Claire , Weiner Howard L.
Published: January 2005

Immunohistochemical staining of 16 brains post mortem from patients with progressive multiple sclerosis and of two biopsy specimens from patients with acute demyelinating disease was performed using a panel of monoclonal antibodies reactive with T cells and T‐cell subsets, B cells, and Ia (HLA‐DR) antigens. Lymphocytic perivascular cuffs were most prominent at the edge of active plaques and were occasionally seen in areas with no evidence of demyelination or macrophage infiltration. Perivascular cuffs consisted predominantly of T cells and Ia+ cells, with many T8+ cells and variable numbers of T4+ cells. T8/T4 ratios in cuffs varied between 1:1 and 50:1. In normal‐appearing white matter, cuffs were sparse and were predominantly T8+. The distribution of T cells in the parenchyma resembled that seen in perivascular cuffs, namely, predominantly T8+ cells and variable numbers of T4+ cells. Many Ia+ cells were present in active lesions, and the majority of these cells appeared, by histological criteria, to be macrophages. Tissue macrophages were also stained lightly by the anti‐T4 antibody. No brain had more T4+ than T8+ cells, determined using both T4 and Leu3a monoclonal antibodies. B1+ cells were rare. These results suggest that the cellular infiltrate in multiple sclerosis consists predominantly of T cells and macrophages and that there is an overrepresentation of T8+ cells compared with T4+ cells.
Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans
Authors: Black Keith L. , Hoff Julian T. , McGillicuddy John E. , Gebarski Stephen S.
Published: January 2005

Leukotrines are pharmacologically active compounds that promote vascular permeability. In this study we sought to determine whether tissue leukotriene–like immunoreactivity was increased in intracranial tumors associated with peritumoral edema. In 20 patients undergoing craniotomy tissue specimens were immediately frozen after removal and tissue leukotriene C4 levels were determined by radioimmunoassay. An index of peritumoral edema was estimated from preoperative contrast‐enhanced computed tomographic scans. There was a significant correlation between brain edema and tissue leukotriene levels (p < 0.003). Metastatic tumors (n = 8) had the highest leukotriene C4 level at 13.8 ± 8.5 pg/mg tissue (mean ± SE) and the highest index of edema 5.7 ± 1.8. The mean leukotriene C4 level in the gliomas (n + 5) ws 6.2 ± 2.3 pg/mg tissue and the edema index was 2.1 ± 0.6. There was no edema and no neoplasma in he temporal lobes removed for seizure (n + 2), and their level of leukotriene C4 was 0.4 ± 0.1 pg/mg tissue. The formation of leukotriene C4 is stimulated by intracranial tumors. Leukotrienes increase blood–brain barrier permeability and may be important in the formation of vasogenic edema surrounding tumors.
Alzheimer'S disease: Monoamines and spiperone binding reduced in nucleus basalis
Authors: Sparks D. Larry , Markesbery William R. , Slevin John T.
Published: January 2005

Levels of dopamine and serotonin, and of their precursors and metabolites, were measured in the nucleus basalis of Meynert (nbM) of patients with Alzheimer's disease and control patients. [3H]Spiperone binding to membrane homogenates of the nbM, indicative of both dopaminergic and serotonergic receptors, was also measured. The nbM from patients with Alzheimer's disease showed significant decreases in both spiperone binding and in the levels of dopamine and serotonin but no decrease in either tyrosine or tryptophan levels. These data indicate a loss of both dopaminergic and serotonergic synapses in the nbM of patients with Alzheimer's disease.
Elevated γ‐aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: Correlation with striatal dopamine loss
Authors: Kish Stephen J. , Rajput Ali , Gilbert Joseph , Rozdilsky Bohdan , Chang Li‐Jan , Shannak Kathleen , Hornykiewicz Oleh
Published: January 2005

We measured the concentration of γ‐aminobutyric acid (GABA), glutamic acid, and o‐phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3‐methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.
Myopathy caused by a deficiency of Ca2+‐adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease)
Authors: Karpati George , Charuk Jeffrey , Carpenter Stirling , Jablecki Charles , Holland Paul
Published: January 2005

Four male patients from two families were first seen with impaired skeletal muscle relaxation that rapidly worsened during exercise. Muscle biopsies from 2 patients were examined by appropriate biochemical and microscopic immunocytochemical techniques. The adenosine triphosphate (ATP)–dependent Ca2+ transport rate was extremely low in a particulate membrane fraction of skeletal muscle, and there was also a marked reduction of the concentration of 100‐kD phosphoprotein, corresponding to Ca2+‐ATPase of sarcoplasmic reticulum, in muscle microsomes. The concentration of immunoreactive Ca2+‐ATPase of sarcoplasmic reticulum was markedly reduced on immunoblots. Evaluation by microscopic immunocytochemical techniques, using one polyclonal and two monoclonal antibodies against sarcoplasmic reticulum Ca2+ transport protein, revealed that the severe reduction of immunoreactive Ca2+‐ATPase was limited to the histochemical type 2 fibers. The deficiency of the Ca2+ transport protein in the sarcoplasmic reticulum of type 2 fibers, which may be the primary expression of a presumed gene defect, can explain the impaired muscle relaxation of the patients. This disease appears to be a clinically, electromyographically, and biochemically distinct metabolic myopathy.
Chronic demyelinating peripheral neuropathy in cerebrotendinous xanthomatosis
Authors: Argov Z. , Soffer D. , Eisenberg S. , Zimmerman Y.
Published: January 2005

Three siblings with chemically proved cerebrotendinous xanthomatosis presented with typical neurological manifestations of dementia and spinocerebellar disorder. Electrodiagnostic tests revealed demyelinating neuropathy in all three. Sural nerve biopsies showed loss of myelinated large fibers, marked Schwann cell proliferation, and onion bulb formation. Teased‐fiber preparations confirmed the occurrence of segmental demyelination and remyelination. We suggest that demyelinating neuropathy is part of the neurological spectrum of cere‐brotendinous xanthomatosis and should be considered in the differential diagnosis of a recessively inherited motor and sensory neuropathy.
Duodenal delivery of levodopa for on‐off fluctuations in parkinsonism: Preliminary observations
Authors: Kurlan Roger , Rubin Allen J. , Miller Charlyne , Rivera‐Calimlim Leonor , Clarke Allan , Shoulson Ira
Published: January 2005

The pathogenesis of on‐off motor fluctuations in parkinsonism remains incompletely understood, but slowed or erratic gastric emptying of orally administered levodopa may be involved. In 3 patients with resistant on‐off fluctuations, direct duodenal continuous infusion of levodopa via a nasoduodenal tube resulted in a heightened therapeutic effect, including a reduction in motor fluctuations. In 1 of these patients, continuous duodenal levodopa infusion produced greater benefit than did intermittent duodenal levodopa administration. Direct duodenal delivery of levodopa lessens the problems with gastric emptying and may be suitable for long‐term therapy in selected patients with resistant on‐off motor fluctuations.
Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease
Authors: Beal M. Flint , Mazurek Michael F. , Chattha Geetinder K. , Svendsen Clive N. , Bird Edward D. , Martin Joseph B.
Published: January 2005

Neuropeptide Y is a 36–amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High‐performance liquid chromatography showed that more than 95% of immunoreactivity co‐migrated with synthetic standards in both Alzheimer's disease and control frontal cortex. Significant reductions in neuropeptide Y–like immunoreactivity were found in eleven cortical regions, the hippocampus, and the locus ceruleus. The regions particularly affected included the temporal lobe, frontal lobe, and occipital cortex. As neuropeptide Y is co‐localized with somatostatin in a considerable proportion of cortical neurons, the loss of immunoreactivity may in part reflect degeneration of these neurons. Further study of the selective vulnerability of these neurons in Alzheimer's disease cortex may provide clues to the nature of the underlying disease process.
Immunohistochemical identification of HTLV‐III antigen in brains of patients with AIDS
Authors: Gabuzda Dana H. , Ho David D. , de la Monte Suzanne M. , Hirsch Martin S. , Rota Teresa R. , Sobel Raymond A.
Published: January 2005

Human T‐cell lymphotropic virus type III (HTLV‐III) has been isolated from neural tissues and cerebrospinal fluid (CSF) of patients with neurological syndromes associated with the acquired immune deficiency syndrome (AIDS) and the virus may be directly involved in the pathogenesis of the syndromes. To detect HTLV‐III antigen in neural tissues from patients with AIDS, immunoperoxidase studies using a goat anti‐HTLV‐III serum were performed on frozen tissue sections of brain, spinal cord, and nerve from 13 patients with AIDS or HTLV‐III–related neurological syndromes. HTLV‐III was cultured from neural tissues or CSF in 11 of 13 of these patients. HTLV‐III antigen was detected in the brains of 5 patients with AIDS and in none of the 13 non‐AIDS control subjects. Rare positively stained cells were seen, frequently associated with capiilaries and often located near microglial nodules. Morphologically, the cells resembled monocyte/macrophages and were found most frequently in the cortex of the frontal, temporal, and parietal lobes. These results provide further evidence that the subacute encephalitis of AIDS is associated with central nervous system infection by HTLV‐III and that monocyte/macrophages are among the infected cell populations.
Glial growth factor—like activity in Schwann cell tumors
Authors: Brockes Jeremy P. , Breakefield Xandra O. , Martuza Robert L.
Published: January 2005

To determine whether glial growth factor (GGF)–like activity is associated with human Schwann cell tumors, we tested extracts from these tumors for their ability to stimulate the proliferation of rat Schwann cells in culture. Extracts from 3 of 3 bilateral acoustic neuromas and from 5 of 7 unilateral acoustic neuromas demonstrated dose‐dependent stimulation similar to that of partially purified bovine pituitary GGF. One neurofibroma also contained high levels of GGF‐like activity, one demonstrated an intermediate level, and three showed low or no activity. Minimal activity was found in one neurofibrosarcoma and in one trigeminal schwannoma. Non–Schwann cell tumors studied included 3 meningiomas, 2 pituitary adenomas, 1 cerebellar astrocytoma, 1 glioblastoma, 1 hemangioblastoma, and 2 metastatic brain tumors. The cerebellar hemangioblastoma demonstrated high GGF‐like activity; the others showed little or no activity. Normal tissues used as control specimens included brain, peripheral nerve, muscle, and fat. Some activity was noted in one nerve biopsy; all others showed minimal or no GGF‐like activity. High‐performance liquid chromatography demonstrated that the GGF‐like activity from two acoustic neuromas eluted in a single peak close to that of bovine pituitary GGF. We conclude that acoustic neuromas contain a factor that is closely related to bovine pituitary GGF and that this factor may have a role in the abnormal proliferation of Schwann cells in these tumors.