bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined short‐term immunotherapy for experimental autoimmune myasthenia gravis
Authors: Pestronk Alan , Drachman Daniel B. , Teoh Robert , Adams Robert N.
Published: January 2005

A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti‐AChR antibody levels by preferential destruction of antibody‐producing B‐lymphocytes. “Memory” lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the “memory” cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant.

Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti‐AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide‐irradiation treatment.

This treatment eliminates the animals' ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar “curative” strategies might be developed for the treatment of patients with severe antibody‐mediated autoimmune disorders, such as myasthenia gravis.
Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin
Authors: Kaufman Seymour , Kapatos Gregory , Rizzo William B. , Schulman Joseph D. , Tamarkin Lawrence , van Loon Glen R.
Published: January 2005

A patient with hyperphenylalaninemia caused by a defect in the synthesis of tetrahydrobiopterin was treated with 6‐methyltetrahydropterin. This synthetic analog of the naturally occurring hydroxylation cofactor tetrahydrobiopterin, when given orally at a daily dose of 20 mg per kilogram of body weight increased depressed plasma and cerebrospinal fluid levels of norepinephrine. At a daily dose of 8 mg/kg, this pterin increased depressed cerebrospinal fluid levels of the biogenic amine metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5‐hydroxyindoleacetic acid. At these doses of 6‐methyltetrahydropterin, there was an improvement of the patient's neurological symptoms, including a pronounced decrease in eye rolling and drooling and a marked increase in muscle strength, coordination, and physical activity.
Intelligence in epilepsy: A prospective study in children
Authors: Bourgeois Blaise F. D. , Prensky Arthur L. , Palkes Helen S. , Talent Barbara K. , Busch Suzanne G.
Published: January 2005

A prospective study tested the stability of the IQ in children with seizure disorders. Seventy‐two children with epilepsy underwent psychological evaluations within two weeks of initial diagnosis and yearly thereafter for an average of 4 years. Forty‐five of the patients also had a nonepileptic sib evaluated in parallel. The mean IQ for all the children with epilepsy was 99.7 (±20.2, standard deviation) at the time of the initial test, not significantly different from the siblings. This score did not change appreciably with time. Eight of the 72 epileptic patients (11.1%), however, had a persistent decrease in IQ of 10 points or more. These patients had a higher incidence of drug levels in the toxic range (p <0.001), their epilepsy was more difficult to control (p <0.005), and their seizures began at an earlier age (p <0.05). Discriminant analysis revealed that the number of drugs to which the patient became toxic and the age at seizure onset were the two best predictors of ultimate IQ. These two predictors correctly classified 71% of all patients as to whether their IQ would drop by 10 or more points during the test period, remain within 10 points of the initial test score, or increase by more than 10 points. Total number of seizures and seizure control were less good predictors, according to this method of analysis. The findings suggest that, in younger children in particular, total seizure control should not be achieved at the price of repeated episodes of drug toxicity.
Senile dementia of the Alzheimer type
Authors: Terry Robert D. , Katzman Robert Katzman
Published: January 2005

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi‐infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and palecortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
Thymectomy‐induced decrease in Tγ cells and OKT8+ cells in multiple sclerosis
Authors: Trotter John L. , Gebel Howard M. , Ferguson Thomas B. , Garvey William F. , Rodey Glen E.
Published: January 2005

Studies were performed on lymphocytes from patients with multiple sclerosis before and after thymectomy (group I) and before and after thymectomy and azathioprine therapy (group II), and from matched control patients with multiple sclerosis, control patients with other neurological diseases, and healthy control subjects. Following treatment the percentage of Tγ cells in both group I and group II patients decreased from above the mean normal control levels to below this level; OKT8 + cell numbers in group I became lower than in any of the control groups; the percentage of concanavalin A‐‐induced suppressor activity, which was initially normal, fell in group II and suggestively but not significantly in group I; and total blood lymphocytes in group I decreased from normal to below control levels. Other tests showed no significant changes with therapy. No significant difference in changes in clinical status were observed after one year in the treated patients compared with matched controls.
Spinal somatosensory evoked potentials in juvenile diabetes
Authors: Cracco Joan , Castells Saladore , Mark Erna
Published: January 2005

Spinal somatosensory Evoked potentials to stimulation of the peroneal nerves in the popliteal fossa were recorded from 46 insulin‐dependent neurologically normal patients with juvenile diabetes. Conduction velocities of these potentials were determined over proximal peroneal nerve, cauda equina, and spinal cord and were compared with those obtained from 46 age‐matched control subjects.

Mean values for overall spinal conduction velocity (L3–C7 spines) and conduction velocity over rostral spinal cord (T6–C7 spines) and peroneal nerve–cauda equina (stimulus to L3 spine) were lower in the diabetic group (p < 0.001). Peripheral nerve conduction velocity alone was slow in 5 patients, and spinal conduction velocity was slow in 8; in 2 patients both peripheal and spinal velocities were slow. This study suggests that in addition to impairment of peripheral nerve function, patients with juvenile diabetes without clinical evidence of neurological involvement can have a defect in spinal afferent transmission.
Carrier detection of sialidosis with partial β‐galactosidase deficiency by the assay of lysosomal sialidase in lymphocytes
Authors: Tsuji Shoji , Yamada Takamichi , Ariga Toshio , Toyoshima Itaru , Yamaguchi Haruyasu , Kitahara Yoshisuke , Miyatake Tadashi , Yamakawa Tamio
Published: January 2005

Lysosomal and plasma membrane sialidase activities in lymphocytes were studied in four patients with sialidosis with partial β‐galactosidase deficiency, four obligate heterozygotes, and three siblings of a patient. Lysosomal sialidase activity in homozygotes was absent, and that in heterozygotes was significantly decreased to 70% of control level. The results indicate that carriers can be detected by the assay of lysosomal sialidase activity of lymphocytes.
Mirror movement: Application of movement‐related cortical potentials
Authors: Shibasaki Hiroshi , Nagae Kazuhisa
Published: January 2005

In a patient withy Kallmann's syndrome (hypogonadotropic hypogonadism and anosmia) manifesting mirror movement, cortical potential associated with unilateral and bilateral simulataneous voluntary middle finger extensions were studied. Premovement negative slope, which has been shown to reflect preparatory excitation of motor cortex corresponding to the voluntary movement, was recorded bilaterally in this patient in spite of intended unilateral hand movement. It is suggested that mirror movement in this particular patient is generated by unintended excitation of the opposite motor contex.
Neurofilament subunit–related proteins in neuronal intranuclear inclusions
Authors: Palo Jorma , Haltia Matti , Carpenter Stirling , Karpati George , Mushynski Walter
Published: January 2005

Well‐preserved nuclei were isolated from the brain of a patient with neuronal intranuclear inclusion disease (NIID). The inclusions in situ stained for proteins and, by immunohistochemical techniques, for the 200K and 68K components of the neurofilament protein triplet but were negative for the 145K neurofilament protein. At the electron microscopic level the inclusions were seen to consist of straight, randomly arranged tubular filaments 8.5 to 9.5 nm in diameter. They were resistant to extraction with hot buffer containing sodium dodecyl sulfate (SDS) and 2‐mercaptoethanol, indicating that the proteins of NIID inclusions are probably cross‐linked by covalent bonds other than disulfide. This feature is also exhibited by the paired helical filaments occurring in brain in Alzheimer's disease. No major differences were found in the polypeptide composition of nuclei in NIID and control nuclei resolved by SDS‐polyacrylamide gel electrophoresis. The inclusions isolated from SDS‐extracted nuclei were shown by immunohistochemical techniques to stain for all three neurofilament subunits, indicating that 145K‐related antigenic sites were uncovered during the extraction procedure.
Autosomal dominant inheritance of hereditary canine spinal muscular atrophy
Authors: Sack George H. , Cork Linda C. , Morris Jeanette M. , Griffin John W. , Price Donald L.
Published: January 2005

Hereditary canine spinal muscular atrophy (HCSMA) is a motor neuron disease in Brittany spiniels. Three phenotypes are recognized (accelerated, intermediate, and chronic) and are distinguished on the basis of rate of progression and age at onset. Breeding studies within a kindered of more than 125 dogs (Brittany spaniel and beagle‐Brittany outcrosses) have established an autosomal dominant inheritance for HCSMA. Pups homozygous for the trait have accelerated disease, whereas heterozygous dogs have intermediate or chronic disease. The reason for the two phenotypes in heterozygotes is under study. HCSMA provides a unique opportunity to study the genetic and pathophysiological mechanisms of a motor neuron disease, and findings may have broad relevance to investigations of autosomal dominant degenerative disorders of the central nervous system.
Nonhemorrhagic venous infarction of the spinal cord
Authors: Kim R. C. , Smith H. R. , Henbest M. L. , Choi B. H.
Published: January 2005

A 71‐year‐old man experienced gradually progressive leg weakness, urinary retention, and mild loss of sensation in dermatomes T8 through T12 bilaterally. After 5 to 6 weeks of illness, he developed flaccid paraplegia and sensory loss below T8. He died 16 weeks after onset of neurological symptoms. Neuropathologically, there was widespread, subtotal necrosis of the spinal cord, largely of nonhemorrhagic character, from T8 downward. Dorsal and anterior median spinal veins were occluded by a partially organized thrombus. Comparison of this case with 19 previously recorded examples of venous infarction of the spinal cord (8 hemorrhagic, 7 nonhemorrhagic, and 4 embolic) suggests major differences in clinical presentation, rate of progression, and length of survival among the three groups.
Exacerbation of myasthenia gravis after removal of a thymoma having a membrane phenotype of suppressor t cells
Authors: Kuroda Yasuo , Oda Ken‐Ichiro , Neshige Ryuji , Shibasaki Hiroshi
Published: January 2005

We describe a case of myasthenia gravis associated with a thymoma having a membrane phenotype of suppressor T cells, as defined by monoclonal antibodies. Thymectomy resulted in exacerbation of the disease, a drastic increase in serum acetylcholine receptor‐antibody titer, and a decrease of the circulating suppressor T cell population. The findings indicate that the etiopathogenic relationship between the thymus and myasthenia gravis is variable and complex.
Lymphomatoid granulomatosis with isolated involvement of the brain
Authors: Schmidt Brain J. , Meagher‐Villemure Kathleen , Carpio Jaime Del
Published: January 2005

A patient with biopsy‐proven lymhomatoid granulomatosis of the brain as the sole manifestation of the disease is described. During 14 months of follow‐up since surgical excision of the cerebral mass, no evidence of recurrent brain involvement or of extracranial lesions has been found. This case is unusual in the confinement of the disease to the central nervous system and in the favorable outcome following surgical treatment alone.
Clinical and genetic variations in the syndrome of adult GM2 gangliodosis resulting from hexosaminidase a deficiency
Authors: Argov Z. , Navon R.
Published: January 2005

Six patients from three families developed adult GM2 gangliosidosis resulting from severe β‐hexosaminidase A deficiency. The clinical picture varied between and within families and included spinocerebellar, various motor neuron, and cerebellar connection syndromes. Psychosis appeared in each family. Involvement of three generations was recorded in one family. The phenotype of adult GM2 gangliosidosis is variable and cannot form a basis for genetic classification. Detailed hexosaminidase determinations in eight patients from five families revealed all patients to have minor quantities of hexosaminidase A (about 15% of normal), with marked increase in hexosaminidase I isozyme.
Gas within intracranial abscess cavities: An indication for surgical excision
Authors: Young Ronald F. , Frazee John
Published: January 2005

Five patients were treated in whom gas within an intracranial abscess cavity was identified by plain roentgenogram, computed tomographic scan, or both. Management by aspiration in three patients was unsuccessful. Total excision of the abscess cavity was eventually required in all five patients, and a persistent extracranial communication was identified and closed in each. One patient died secondary to transtentorial herniation and severe brainstem injury; the other four recovered fully. Although certain anaerobic organisms may produce gas in the absence of a communication to the outside of the body, such production is uncommon. Total surgical excision is recommended for gas‐containing abscesses because it allows removal of the mass lesion and identification and closure of possible persistent extracorporal communication.
Nystagmus in motor neuron disease: Clinicopathological study of two cases
Authors: Kushner Michael J. , Parrish Margaret , Burke Alan , Behrens Myles , Hays Arthur P. , Frame Boy , Rowland Lewis P.
Published: January 2005

Two patients with amyotrophic lateral sclerosis proved postmortem had nystagmus in addition to typical clinical signs of motor neuron disease. The first patient had gaze‐evoked rotatory nystagmus that was followed by horizontal nystagmus in the primary position with supranuclear paresis of horizontal gaze and upgaze. The second patient had rotatory nystagmus that was evoked by lateral gaze, with normal range of eye movements. Nystagmus is so rare in motor neuron disease that these observations may imply another disease, but postmortem examination did not provide any other explanation. These two cases add to the increasing evidence that motor neuron disease comprises a heterogeneous group of disorders.
Human leukocyte interferon administration to patients with symptomatic and suspected rabies
Authors: Merigan Thomas C. , Baer George M. , Winkler William G. , Bernard Kenneth W. , Gibert Claude G. , Chany Charles , Veronesi Ricardo ,   The Collaborative Group
Published: January 2005

Body fluids and brain tissue from rabid human patients have demonstrated only low titers of interferon. Therefore, pharmacokinetic studies of systemically administered and locally injected leukocyte interferon were performed in 2 North American patients with suspected rabies who showed no clinically important side effects of this therapy. Similar therapy was given to 5 patients with symptomatic rabies in Europe and America. Although no prolongation of the clinical course was seen in 3 patients given high‐dose intraventricular and systemic therapy, treatment was not intiated until between 8 and 14 days after symptoms were seen. The intraventricular dosage regimen produced cerebrospinal fluid levels that appeared to fall progressively over the 24 hours after injection and demonstrated good but somewhat delayed distribution into the lumbar sac. Titers produced by this therapy were 30‐ to 10,000‐fold higher than those normally observed in this infection, however. In the patients treated at the highest dosage, a diminished and delayed antirabies neutralizing antibody titer was observed, probably a result of the administration of the exogenous interferon.
Nonconvulsive status epilepticus following metrizamide myelography
Authors: Pritchard Paul B. , O'Neal David B.
Published: January 2005

Epileptic seizures are a known complication of metrizamide myelography. To our knowledge, this is the first report of a case of nonconvulsive status epilepticus of the absence type following metrizamide myelography. There was symptomatic and electroencephalographic improvement after intravenous administratration of antiepileptic drugs, and there was no neurological residual. Nonconvulsive status epilepticus should be considered when impairment of consciousness supervenes after radiographic procedures using metrizamide.
Progressive cerebral ischemia antedates cerebrovascular symptoms by two years
Authors: Meyer John Stirling , Rogers Robert L. , Mortel Karl F.
Published: January 2005

Prospective longitudinal cerebral blood flow values were serially plotted over a four‐year interval against the course of cerebral ischemia before, during, and after onset of clinical symptoms. Of 161 normal subjects (mean age, 62 years), 86 were risk free and 75 had hypertension, heart disease, diabetes mellitus, and/or hyperlipidemia. Twenty‐one subjects developed cerebrovascular symptoms during the prospective trial. Mean hemispheric cerebral blood flow values were significantly lower for at risk than for risk‐free subjects. Symptomatic subjects showed lower values than those in either of the two asymptomatic groups at every session. Statistical analysis of cerebral blood flow values for symptomatic patients compared one and two years prior to onset of symptoms, at the onset of symptoms, and 1 year later showed reductions compared to asymptomatic risk‐factored subjects tested in a similar prospective manner. Measurable declines in cerebral perfusion accompany development and progression of aortocerebral atherosclerosis prior to clinical appearance of signs and symptoms of cerebrovascular disease. If confirmed, these observations should permit the institution of preventive medical and/or surgical interventive measures and an evaluation of their outcome.
Dystonia in 61‐year‐old identical twins: Observations over 45 years
Authors: Eldridge Roswell , Ince Susan E. , Chernow Bart , Milstien Sheldon , Lake C. Raymond
Published: January 2005

We examined 61‐year‐old identical twin women of Jewish extraction with a probable autosomal recessive form of torsion dystonia. The dystonia in each was relatively mild and discovered only because a young relative developed dystonia. The twins were said to be discordant for dystonia, but personal evaluation led to the diagnosis of dystonia in both. Their slow course, with prolonged spontaneous remission in one twin, is in contrast to that described in most published reports. Although similar in mode of onset and initial course, the twins were dissimilar in age at onset, influence of pregnancy, diurnal variation in symptoms, need for medication, later course, and degree of disability at age 61. Normal plasma levels of norepinephrine and dopamine‐beta‐hydroxylase are consistent with autosomal recessive hereditary torsion dystonia.

The importance of personal evaluation of key family members in establishing the correct genetic basis for a heterogeneous group of disorders, such as the hereditary dystonias, is stressed.
Computed tomography in the diagnosis of Wernicke's encephalopathy: A radiological‐neuropathological correlation
Authors: Mensing J. W. A. , Hoogland P. H. , Slooff J. L.
Published: January 2005

A case of Wernicke's encephalopathy with pathological verification is reported. Results of computed tomography scanning performed one day after admission of the patient, a male alcoholic, strongly suggested Wernicke's encephalopathy and were in agreement with the subsequent postmortem findings.
Myasthenia gravis and myasthenic syndromes
Authors: Engel Andrew G.
Published: January 2005

More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) {119} and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) {36}. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG {87}, passive transfer with IgG of several features of the disease from human to mouse {149}, localization of immune complexes (IgG and complement) on the postsynaptic membrane {30}, and the beneficial effects of plasmapheresis {20, 123}. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert‐Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.
Nuclear magnetic resonance imaging in evaluation of clinical stroke syndromes
Authors: DeWitt L. Dana , Buonanno Ferdinando S. , Kistler J. Philip , Brady Thomas J. , Pykett PhD Ian L. , Goldman Mark R. , Davis Kenneth R.
Published: January 2005

Proton nuclear magnetic resonance (NMR) imaging was performed on normal volunteers and patients with various types of clinical strokes. True three‐dimensional volumetric data were obtained for subsequent reconstruction of images at various orientations, including transverse, coronal, and sagittal, and for specific matching to x‐ray computed tomographic planes. A variety of radiofrequency pulse sequences was used to generate images weighted by the NMR parameters spin density (ρ) and spin‐lattice (T1) and spin‐spin (T2) relaxation times. Quantitative T1 data and qualitative T2 information were obtained from appropriate sequences. Proton NMR images embodying T1 information provided adequate delineation of normal intracranial anatomical structure and a high level of gray matter–white matter contrast; high lesion detection sensitivity in various clinical forms of stroke was seen in images providing both T1 and T2 information. T1 and T2 relaxation times were prolonged in embolic, thrombotic, and watershed infarctions as well as in lacunae; shortening of T1 and T2 was found in hematomas. Serpiginous vessels in an arteriovenous malformation were seen that had particular pulse sequences.
Galactose neuropathy: Impact of chronic endoneurial edema on nerve blood flow
Authors: Myers Robert R. , Powell Henry C.
Published: January 2005

Periperal neuropathy induced by galactose feeding results in endoneurial edema with increased tissue pressure and ultimate demyelination of nerve fibers. To assess the role of ischemia in the pathogenesis of this neuropathy, nerve blood flow was measured 6 months after the start of galactose ingestion, between the onset of edema and nerve fiber changes. Measurement was carried out by a noninvasive technique involving the use of [14C]iodoantipyrine as a radioactive tracer of tissue perfusion. A significant decline in nerve blood flow was found, which correlated positively with increased nerve water content as quantified by a microgravimetric technique. We sought to establish the pathogenic role of nerve edema in the development of schwannopathy and demyelination by morphological examination. It was found that Schwann cells appeared normal in areas of the peripheral nervous system in which edema does not occur, such as spinal ganglia and roots, whereas in regions in which there was edema, massive glycogen accumulation in Schwann cells and demyelination occurred. These findings suggest that edema, rather than hyperactivity in the sorbitol pathway, is responsible for the pathological changes in galactosemic neuropathy and that ischemia resulting from edema and increased endoneurial fluid pressure is the mechanism responsible for fiber injury.
Quality‐specific taste changes in multiple sclerosis
Authors: Catalanotto Frank A. , Dore‐Duffy Paula , Donaldson James O. , Testa Marcia , Peterson Margaret , Ostrom Karin M.
Published: January 2005

Taste sensitivity in 79 patients with multiple slcerosis (MS) and 65 age‐ and sex‐matched control subjects was measured with a sip‐and‐spit, suprathreshold scaling, magnitude estimation procedure using six concentrations each of sodium chloride, sucrose, citric acid, and quinine hydrochloride. Results were analyzed with a taste scoring system and by plotting psychophysical functions (log concentration versus log magnitude estimate) normalized to 1.0 M sucrose. Gender did not affect taste scores, but age was inversely related, so the results were analyzed by an analysis of covariance with age as the covariant. There was a significant alteration in taste sensitivity in the subjects with MS for sodium chloride and quinine hydrochloride stimuli but not for sucrose and citric acid; these results were confirmed by a separate analysis of the psychophysical functions. Some of the MS taste scores correlated with MS functional and physical disability scores. Taste sensitivity was not correlated with clinical history or presence of facial symptoms.
Neonatal Citrobacter meningitis: Pathogenesis of cerebral abscess formation
Authors: Foreman Susan D. , Smith Edward E. , Ryan Nell J. , Hogan Gwendolyn R.
Published: January 2005

In 2 premature infants with brief survival, the major pathological feature of Citrobacter meningitis consisted of vasculitis and infarction with necrosis and liquefaction of large portions of the white matter of the hemispheres. Areas of decreased density demonstrated on computed tomographic head scan represented infarction with necrosis, liquefaction, and cavitation and not a classic abscess. This finding has clinical significance, because surgical drainage of liquefied infarcts is rarely indicated and could further damage the relatively preserved cortex.
Idiopathic dystonia‐parkinsonism with marked diurnal flucuation of symptoms
Authors: Sunohara Nobuhiko , Mano Yukio , Ando Kazuya , Satoyoshi Eijiro
Published: January 2005

Studies were performed on 5 patients with idiopathic dysotnia‐parkinsonism, each of whom had minor dystonic movements and parkinsonian symptoms with marked diurnal fluctuation. Levels of homovanillic acid and 5‐hydroxyindoleacetic acid were not defferent from those in controls. Considerable improvement in dystonic movements and parkinsonian symptoms was obtained with a small dose of L‐dopa, trihexyphenidyl hydrochloride, amantadine, or bromocriptine hydrochloride. Electrophysiological investigation confirmed that the dystonic movements, which became remarkably worsened on attempted movement, contributed importantly to the diurnal fluctuation of symptoms.
Comparison of survival times of mice inoculated with brain tissue from various neurological diseases
Authors: Greenham Leighton W. , Peacock David B.
Published: January 2005

Mice inoculated intracerebrally before the age of 5 days with homogenates of autopsied brain tissue from patients with Creutzfeldt‐Jakob (C‐J), Alzheimer's, or Pick's diseases showed highly significant decreases in life span when compared with sham‐inoculated control mice. With C‐J disease there was strong indication of horizontal transmission of the agent to unionculated mice caged with the inoculated mice. While the results with C‐J disease were not unexpected in view of the known infectious etiology of the disease, the results obtained with Alzheimer's and Pick's diseases suggest that previously undetermined infectious or toxic agents may be associated with these who diesease, which currently have unresolved etiologies. Mice inoculated with autopsied brain tissue from patients with multiple scelrosis or subacute sclerosing panencephalitis had life spans similar to those of the control mice.
Inflammatory myopathies: Part 1
Authors: Mastaglia Frak L. , Ojeda Victor J.
Published: January 2005

The inflammatory myopathies have diverse clinical and pathological features and multiple etiologies. Some are confined to a single muscel or group of muscles (e.g., orbital myositis and localized nodular myositis) while others are diffuse. Infective forms may be due to viral, bacterial, fungal, protozoal, or parasitic organisms. Viruses may cause acute self‐limited forms of myositis and have been isolated from muscle in some cases of acute rhabdomyolysis and inclusion body myositis. They have also been implicated in some cases of acute rhabdomyolysis and inclusion body myositis. They have also been implicated in some cases of congenital myopathy and in polymyositis and dermatomyositis, but there is no evidence of viral invasion of muscle in these conditions. In polymyositis and dermatomyositis there are derangements in humoral and cellular immune function, and recent evidence suggests an underlying disturbance of immunoregulation. The roles of genetic factors, drugs, and Toxoplasma infection have been under scrutiny. There is increasing recognition of immunological and pathological differences in polymyositis and juvenile and adult dermatomyositis, and in cases with associated connective tissue diseases, suggesting different underlying pathogenetic mechanisms. Inclusion body myositis, eosinophilic myositis, and granulomatous myositis can be separated from the other idiopathic inflammatory myopthies because of distinctive clinical and pathological features and this may also reflect different mechanisms of muscle injury. Recent developments in the treatment of the idiopathic inflammatory myopathies include the use of plasmapheresis and total‐body irradiation in cases that are resistant to corticosteroids and immunosuppressive drugs.
Atypical presentation of progressive supranuclear palsy
Authors: Davis P. H. , Bergeron C. , McLachlan D. R.
Published: January 2005

Four pathologically documented cases of profressice supranuclear palsy are reported. Two patients exhinited severe dementia and 2 parkinsonism; none had the classic opthalmoplegia. On retrospective analysis, clues to the diagnosis included early prominent gait disturbance, apraxia of eyelid opening in 1 patient, lack of tremor, poor response to levodopa‐carbidopa, and severe rigidity with a posture of neck extension terminally in 1 patient. The clinical presentation of progressive supranuclear palsy, therefore, is not as stereotyped as previously thought, and the diagnosis can be overlooked if one adheres rigidly to the classic diagnostic criteria.
Fatal infantile mitochondrial myopathy and renal dysfunction caused by cytochrome c oxidase deficiency: Immunological studies in a new patient
Authors: Zeviani Massimo , Nonaka Ikuya , Bonilla Euardo , Okino Eizo , Moggio Maurizio , Jones Sara , DiMauro Salvatore
Published: January 2005

A 3‐month‐old female infant had profound generalized weakness, de Toni‐fanconi‐Debre syndrome, and lactic acidosis. She required asisted ventilation and died at the age of 8 months. Muscle biosy showed accumulated of mitochondria, glycogen, and lipid droplets. Histochemical reaction and immunocytochemical stain for cytochrome c oxidase showed very weak normal in intrafusal fibers of the muscle spindle. In crude extracts of the patient's muscle, cytochrome c oxidase activity was undetectabel and enzyme‐linked immunosorbent assay showed decreased reaction at all dilutions of antiserum. These data indicate that the amount of immunoreactive enzyme protein is markedly decreased in muscle of patients with fatal infantile cytochrome c oxidase deficiency and renal dysfunction.
The initial diagnosis of multiple sclerosis: Clinical impact of magnetic resonance imaging
Authors: Gebarski Stephen S. , Gabrielsen Trygve O. , Gilman Sid , Knake James E. , Latack Joseph T. , Aisen Alex M.
Published: January 2005

Thirty patients in whom the initial diagnosis of multiple sclerosis was clinically entertained underwent cranial magnetic resonance imaging (MRI) in close temporal relationship to cranial x‐ray computed tomography (CT), electrodiagnostic studies (visual evoked responses, brainstem auditory evoked responses, and somatosensory evoked responses), and cerebrospinal fluid analyses (Oligoclonal bands, myelin basic protein, and IgG/albumin ratio). In 26 of the 30 patients, MRI demonstrated lesions consistent with multiple sclerosis that corresponded, at least in part, with the clinically expected neuroanatomical lesion distribution. Two of the 4 patients with normal MRI had normal electrodiagnostic studies and cerebrospinal fluid analyses, and the other 2 had a single abnormal or equivocal electrodiagnostic study. All 26 patients with abnormal MRI had at least one other abnormal laboratory test. CT revealed only the largest lesions, and in the patients with abnormal CT, MRI demonstrated even more lesions. MRI, in this limited series, proved to be a strong tool in the initial diagnosis of multiple sclerosis; it may prove to be the single best test, with a sensitivity exceeding that of electrodiagnostic studies and cerebrospinal fluid analysis.
The critical role Wernicke's area in sentence repetition
Authors: Selnes Ola A. , Knopman David S. , Niccumm Nancy , Rubens Alan B.
Published: January 2005

The anatomical correlates of persistent deficits in sentence repetition were studied in a group of 32 right‐handed patients with fluent aphasia caused by left hemisphere ischemic stroke. Patients whose ability to repeat remained impaired by 6 month after onset almost withoutexveption had damage to Wernicke's area had impaired repetition 6 months after onset. The most consistent lesion correlating with chronic impairment of repetition, therefore, was one destroying parts or all of Wernicke's area. Lesion outside of this area typically resulted in milder impairment of repetition that resolved within a few months. Only 5 patients had no repetition impairment when tested early (1 month after onset). These patients all had lesions anterior to the rolandic fissure, some including Broca's area.
Nucleus tractus solitarius lesions elevate pulmonary arterial pressure and lymph flow
Authors: Darragh Teresa M. , Simon Roger P.
Published: January 2005

The effects of lesions of the nucleus tractus solitarius (NTS) on pulmonary vascular pressure and pulmonary lymph flow were investigated in 6 halothane‐anesthetized sheep. After lesions of the NTS were created using bilateral thermocoagulation, pulmonary artery pressure rose to 150% of baseline and remained elevated for the 3‐hour duration of the experiment. Systemic and left atrial pressures did not change. Sham NTS lesions and lesions lateral of NTS produced no changes. These experiments demonstrate that lesions of the central nervous system can alter pulmonary vascular pressures and transcapillary fluid flux independently of effect upon the systemic circulation. These findings may findings may have relevance for the understanding of neurogenic pulmonary edema in humans.
Cerebral cortical function in infants at risk for sudden infant death syndrome
Authors: Clancy Robert R. , Spitzer Alan R.
Published: January 2005

Cerebral cortical function was prospectively examined by electroencephalography (EEG) in 3 subgroups of 257 infants at risk for sudden infant death syndrome (SIDS). Group 1 consisted of apparently healthy infants with near‐miss SIDS episodes; Group 2 consisted of siblings of SIDS victims; and Group 3 consisted of neurologically suspect infants with apnea. The usual abundance and distribution of sharp EEG transients (SETs) were determined from 69 Group 1 infants. EEGs were interpreted as abnormal in the presence of ictal apnea, excessively abundant SETs, or immaturity of EEG background for conceptional age. Ninety percent of infants in Group 1 had entirely normal EEGs. There was no significant difference in the abundance or distribution of SETs between infants with normal breathing patterns and those with excessively periodic respirations. Nonictal apnea was recorded in 7% of Group 1 infants. The unexpected diagnosis of ictal apnea was confirmed in 2 Group 1 infants (1.2%), and 5 (2.9%) had excessive SETs but no recorded seizures. Only 4 infants (2.3%) had abnormally immature EEGs for conceptional age. Nonictal apnea occurred in 5 of 33 (15.2%) Group 3 infants and ictal apnea was confirmed in 2 others (6.1%). We conclude that the majority of Group 1 and 2 infants have normal cerebral cortical activity between and during apnea and that central nervous system cortical immaturity, as measured by EEG, plays no important role in the pathogenesis of SIDS. SETs are commonly recorded in these infants and must be conservatively interpreted. However, an EEG examination was critical in establishing the unexpected diagnosis of ictal apnea in a small percentage of Group 1 and 3 infants and materially influenced subsequent evaluation, management, and prognosis.
Acute traumatic midbrain hemorrhage
Authors: Ropper Allan H. , Miller Douglas C.
Published: January 2005

A syndrome resulting from traumatic midbrain hemorrhage is described in 5 patients, 3 of whom had intracranial pressure measurements and 2 of whom had pathological examinations. The major clinical signs, evident immediately after injury, are coma, dilated (4 to 8 mm diameter) pupils that are fixed to light and dark, diminished limb tone, and impaired horizontal eye movements. The hemorrhages are single and linear or oval‐shaped in the midsagittal rostral midbrain, extending several millimeters bilaterally. The appearance of the hematoma may be delayed on computed tomographic scanning, but early abnormalities of wave V of the brainstem auditory evoked potentials aid in diagnosis. Pathological features suggest that secondary brainstem distortion occurred soon after injury, perhaps resulting from a transiently raised intracranial pressure, but shearing injuries caused by acceleration–deceleration forces were also found.
A quantitation of myelin‐associated glycoprotein and myelin basic protein loss in different demyelinating disease
Authors: Gendelman Howard E. , Pezeshkpour Gholam H. , Pressman Norman J. , Wolinsky Jerry S. , Quarles Richard H. , Dobersen Michael J. , Trapp Bruce D. , Kitt Cheryl A. , Aksamit Allen , Johnson Richard T.
Published: January 2005

The loss of myelin‐associated glycoprotein (MAG) and myelin basic protein (MBP) was compared by quantitative immunocytochemistry in demyelinating lesions of measles encephalomyelitis (ME), multiple sclerosis (MS), and progressive multifocal leukoencephalopathy (PML). Serial sections from paraffin‐embedded tissue were reacted with antisera for MAG and MBP, and areas of staining loss were compared morphometrically. Lesions in ME showed MAG loss equal to that of MBP, lesions of PML showed MAG loss greater than that of MBP, and MS lesions showed a mixture of patterns. These data demonstrate distinctive patterns of MAG and MBP loss in these three diseases.
Cerebal norepinephrine depletion enhances recovery after brain ischemia
Authors: Busto Raul , Harik Sami I. , Yoshida Shinichi , Scheinberg Peritz , Ginsberg Myron D.
Published: January 2005

Monoamine neurotransmitters, especially norepinephrine (NE), may have an important role in the pathophysiological aspects of postischemic cerebral dysfunction. In previous studies of post‐decapitation–induced ischemia, we found that NE depletion caused a delay in glycogen breakdown but did not influence any of the other known biochemical abnormalities that accompany brain ischemia. In this study, we have turned to a model of transient incomplete and diffuse forebrain ischemia in the rat to examine the effects of cerebral NE depletion on the recovery after brain ischemia of levels of high‐energy phosphate compounds, products of intermediary oxidative metabolism, and free fatty acids. We found that a unilateral lesion of the locus ceruleus and the resultant depletion of NE in the ipsilateral cerebral cortex had no effect on sham‐operated controls nor on rats subjected to ischemia alone. However, in rats subjected to ischemia followed by 15 minutes of recirculation, the NE‐depleted cerebral cortex had significantly higher phosphocreatine and adenosine triphosphate levels and energy charge, and lower adenosine monophosphate and docosahexaenoic acid concentrations. With longer periods of recirculation, these side‐to‐side differences were not apparent. These results suggest that activity of the central NE systems during transient brain ischemia has deleterious effects on the biochemical recovery of the cerebral cortex from severe ischemic insults.
Chickenpox with delayed contralateral hemiparesis caused by cerebral angiitis
Authors: Kamholz John , Tremblay Gerald
Published: January 2005

Chickenpox and herpes zoster ophthalmicus are caused by the same virus. Herpes zoster ophthalmicus can be followed by contralateral hemiparesis, which is thought to be caused by spread of varicella‐zoster virus to blood vessels contiguous to the trigeminal nerve and its branches. We report what we believe to be the first case of a patient with chickenpox followed by hemiparesis in whom there was angiographic evidence of an associated vasculitis similar to that found with herpes zoster ophthalmicus.
Acute improvement in exacerbating multiple sclerosis produced by intraenous administration of mannitol
Authors: Stefoski D. , Davis F. A. , Schauf C. L.
Published: January 2005

The mode of action of adrenocorticotropic hormone (ACTH) treatment in exacerbating multiple sclerosis was studied by short‐term infusions of agents that mimic specific and limited pharmacological actions of ACTH and observing for temporally phase‐locked clinical changes. The study was double blinded, and agents were administered while the patients were being treated with a standard course of 10‐day intramuscular ACTH therapy (40 U twice daily). Antiedema, alkalotic–hypocalcemic, extraadrenal, and sodium‐retaining actions were studied using infusions of mannitol, sodium bicarbonate, ACTH, and sodium chloride, respectively. Seven of 8 patients receiving placebo infusions (2.5% glucose) showed no significant clinical change and 1 exhibited an equivocal improvement. Five of 9 patients receiving mannitol showed definite signs of clinical improvement phase‐locked to drug administration, with subsequent gradual reversal to baseline. Similar improvements occurred with infusions of NaHCO3 in 5 of 8 patients and of ACTH in 4 of 8 patients. Three of 7 patients given NaCl infusion showed possible mild improvements. The results indicate that mannitol and NaHCO3 induced transient acute improvement in signs at the 95% confidence level in patients with exacerbating multiple sclerosis, with ACTH having a similar effect at the 90% confidence level. These agents mimic some of the known effects of ACTH, which may be important in the therapeutic action of ACTH in multiple sclerosis. A possible role for mannitol and high‐dose ACTH in the treatment of demyelinating disease warrants further study.
Japanese encephalitis: Immunocytochemical studies of viral antigen and Inflammatory cells in fatal cases
Authors: Johnson Richard T. , Burke Donald S. , Elwell Michael , Leake Colin J. , Nisalak Ananda , Hoke Charles H. , Lorsomrudee Wanida
Published: January 2005

The distribution of virus and the composition of the mononuclear inflammatory response were studied in the brains of 7 children who died with Japanese encephalitis. Viral antigen was localized to neurons, with greatest involvement in the thalamus and brainstem. Quantitation of perivascular inflammatory responses showed a preponderance of T cells, but only 7 to 30% of these cells were T suppressor/cytotoxic cells. Inflammatory cells invading the parenchyma were predominantly macrophages with small numbers of T cells. B cells remained localized to perivascular cuffs. Viral antigen was progressively cleared in patients with survival of 6 days or more.