Dementia of frontal lobe type due to adult polyglucosan body disease.

We describe a patient with adult polyglucosan body disease (APBD) who presented with a dementia of frontal lobe type (FLD), with a neurogenic bladder but no symptoms of sensory motor peripheral neuropathy. Diagnosis was made from a cerebral biopsy specimen which showed an accumulation of intra-axonal polyglucosan bodies in the central nervous system. This case differs from the usual presentation, in which gait disturbance is the main symptom and diagnosis is possible by sural nerve biopsy. Little is known about the neuropsychological pattern of APBD dementia but FLD has not previously been described. APBD is a heterogeneous clinical entity of unknown cause. This diagnosis must be considered in elderly patients with dementia.

Visuo-spatial attention and psychomotor performance in elderly community residents: effects of age, gender, and education.

In cross-sectional analysis of 1,799 subjects of the Paquid Research Program, an epidemiological study on brain aging conducted in the Bordeaux area (France), we have studied the effects of age, gender, and education level on psychometric tests requiring visuo-spatial focused attention and psychomotor performance. Although previous studies suggest that normal aging produces no significant change in focused attention, we did observe lower attentional abilities and lower speed of execution with increasing age. Female gender and low education level were also related to poorer attention and psychomotor performance. As the effects of these individual factors are difficult to disentangle from each other on the small samples of subjects used in group studies, epidemiological surveys seem useful to provide a better understanding of the neuropsychology of aging.

[Demonstration of dissociation between frontal and temporal lesions in man on two versions of delayed non-matching recognition tests used in monkeys]. / Mise en évidence chez l'homme, d'une dissociation entre les effets de lésions frontales et temporales sur deux versions de l'épreuve de reconnaissance par non appariement retardé, utilisée chez le singe.

11 patients with frontal lobe lesions (F group), 9 patients with temporal lobe lesions (T group) and 18 normal control subjects (C group) were tested on two versions of the delayed non matching-to-sample task using either different pairs (DNMTS) or the same pairs of objects (RECURRENT) on successive test trials. The results revealed that the DNMTS task was sensitive to memory impairment but did not differentiate the two experimental groups. In contrast, the recurrent version of the task showed a dissociation between the two pathologies. Thus, whereas patients of group T exhibited an accelerated rate of forgetting as a function of the retention interval, patients of group F were impaired whatever the retention interval.

RU 24722, a new eburnamine derivative, induces selective alterations in cerebral glucose utilization in freely moving rat.

The effect of a new eburnamine derivative, RU 24722, a putative phasic activator of catecholaminergic systems on local cerebral glucose utilization was studied in freely moving rats 15 min, 90 min and 6 h after the intraperitoneal administration of the drug (25 mg/kg). Of the 53 brain regions examined, 9 exhibited significant time-dependent increases of glucose utilization (up to 45-55%). Some changes were early and transient, as in the substantia nigra reticulata and the paraventricular nuclei. Other areas showed sustained (median septal nucleus) or delayed increases of glucose utilization (lateral septum, dorsal subiculum, hippocampal fimbria, fronto-parietal motor cortex and ventral cochlear nucleus). No significant alterations of glucose utilization could be elicited in the locus coeruleus and raphe nuclei, and none of the brain regions showed a decrease in glucose consumption. Our findings suggest that RU 24722 preferentially stimulates the activity in some brain areas involved in cognitive, vegetative and locomotor functions.

Distribution of cytochrome oxidase in rat brain: studies with diaminobenzidine histochemistry in vitro and [14C]cyanide tissue labeling in vivo.

Studies in experimental animals and post-mortem studies in humans have indicated that the level of the mitochondrial enzyme cytochrome oxidase within brain anatomical pathways is regulated by the long-term functional use of those pathways. To study this relationship, we have measured cytochrome oxidase spectrophotometrically in punch biopsies from different brain regions of rat. We compared these assays against results from the diaminobenzidine histochemical technique. We found a high degree of correlation (r = 0.90) between the density of diaminobenzidine reaction product and enzyme activity. This validates the usefulness of the diaminobenzidine technique for anatomical localization and measurement of this enzyme. To study the feasibility of using radioactive cyanide as an in vivo ligand of cytochrome oxidase, we performed quantitative autoradiographic analysis of rat brains of animals given an intravenous bolus injection of [14C]cyanide. Analysis of the arterial blood curve indicated a complex redistribution of cyanide between red blood cells, plasma, and tissues. Brain labeling reached peak levels at 1 min and then fell despite rising concentrations of free plasma cyanide. Analysis of autoradiographic images revealed good anatomical resolution. The density of labeling in individual structures over time failed to show a strong correlation with cytochrome oxidase activity or diaminobenzidine reaction product.

Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans.

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100 g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.

Decreased biosynthesis of saturated C20-C24 fatty acids by the trembler mouse sciatic nerve.

Excised Trembler mouse sciatic nerves synthesize, from acetate, only minute amounts of C20 and C22 saturated fatty acids (about 1 10 of the normal value) and almost no lignoceric acid. The elongation activity is localized in the microsomal fraction. The microsomes from Trembler sciatic nerves can elongate stearoyl-CoA into C20, C22 and C24 saturated fatty acids. The elongation rate is only 1 3 of the normal value, whereas the stearoyl-CoA hydrolysis is 3 times higher than in the control; the malonyl-CoA concentration remains at the same level in microsomes from normal and trembler sciatic nerves. When ATP-Mg(2+) is added to the Trembler microsomes, the stearoyl-CoA hydrolysis is reduced, the stearoyl-CoA concentration remains nearly normal and the elongation reaches an almost normal level.

[Fractionation of a sciatic nerve homogenate from normal, trembler and quaking mice on a continuous sucrose gradient]. / Fractionnement d'un homogénat de nerf sciatique de souris normale, Trembler et quaking sur gradient continu de saccharose.

Two fractions, characterized by biochemical criteria [quantity and density of particulate material, localization of myelin specific protein--Po, P1 and Pr--and of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and of 5'-nucleotidase], were isolated from sciatic nerve homogenate of normal, Trembler and quaking, young and adult Mice, on a continuous sucrose gradient. The fraction, at 0.58-0.6 M, the richest in membrane particles contains the myelin. The fraction at 0.7-0.75 M should contain the plasma membrane of the Schwann cell which synthesizes myelin.

Adrenomyeloneuropathy: demonstration of inclusions at the level of the peripheral nerve.

A patients is reported with a progressive neurological disease which started at the age of 19 years and included spasmodic paraplegia, urinary disorders, impotence and neuropathic signs. The neurological syndrome was associated with adrenal failure. The disease led to death within 5 years. In this characteristic picture of adrenomyeloneuropathy, biopsy of peripheral nerve disclosed lamellar inclusions in the Schwann cell cytoplasm. Such structures, which have already been observed in the sural nerve of some adrenoleukodystrophy cases reported previously, are described for the first time in a case of adrenomyeloneuropathy.

Guillain-Barré syndrome and Hodgkin's disease--ultrastructural study of a peripheral nerve.

A 46-year-old male patient developed the Guillain-Barre syndrome and recovered completely within 3 months. He had been treated 5 years previously for Hodgkin's disease, and during the neurological syndrome, relapse of the malignant lymphoma was discovered. On neuro-muscular biopsy, lymphocytes were observed penetrating Schwann cells. These neuropathological aspects confirm the auto-immune character of the nervous involvement.

[Biochemical aspects of myelinogenesis in the peripheral nervous system]. / Aspects biochimiques de la myélinogenèse dans le système nerveux périphérique.

The excised sciatic nerve of the trembler mouse synthesizes minute amounts of C20 and C22 saturated fatty acids as compared to the normal PNS. No lignoceric acid synthesis is observed. The microsomal fraction contains however an elongase able to synthesize with nearly normal levels the saturated very long chain fatty acids.

[Pathology of myelin; a biochemical approach]. / Pathologie de la myéline, une approche biochimique.

In the sciatic nerves of the Trembler mouse, considered as a good model for the study of the hereditary hypertrophic neuropathies, the levels of the different classes of lipids, of alkanes and of very long chain fatty acids are reduced. Those of cholesterol esters and lysophosphatidylcholine are increased.

[Adrenomyeloneuropathies]. / Les adrénomyéloneuropathies.

An adrenomyeloneuropathy is observed in a patient died at 24 years old after an illness of five years duration. These case is peculiar by the presence of lamellar cytoplasmic inclusions in the Schwann cells. Adrenomyeloneuropathy is an adult variant of adrenoleucodystrophy. This sex linked recessive disorder is related to an excessive amount of long chain fatty acids.

Lipid composition of sciatic nerve from dysmyelinating trembler mouse.

The amounts and the distribution of the various lipids were studied in the sciatic nerves from normal and trembler mice. When compared to the normal, the total lipidic amount was reduced by 66% in the trembler mouse, and each class of lipid was decreased nearly the same way, except for the cholesterol esters the value of which increased five times. The level of each individual phospholipid was decreased, phosphatidylcholine being the least affected and phosphatidylserine the most altered.

[Cerebral infarction and migrainous attack. Angiographic and CT scan studies (author's transl)]. / Infarctus cérébral au cours d'un accès migraineux. Etude angiographique et tomodensitométrique.

A lateral homonymous hemianopia appareared in a 40 years old housewife during a migrainous attack and persisted as sequella. Angiographic study was normal and CT scan showed an area of low density at the right occipital level enhancing with heterogenous aspect after the iodinate injection. The occurrence of a cerebral infarction during a migrainous attack is probably due to numerous factors.

Polyneuropathy in Waldenström's macroglobulinemia. Deposition of M component on myelin sheaths.

A chronic sensory neuropathy was the initial symptom in a case of Waldenström's macroglobulinemia in a 53-year-old woman. Ultrastructural analysis of a biopsied peripheral nerve revealed a modification of the lamellar structure of the myelin sheath. Immunofluorescent microscopy showed IgM-positive deposits on the myelin sheath. The monoclonal globulin (M component) present in the myelin appears to be a causative factor in the neuropathy.

The inhibition of mitochondrial DNA polymerase gamma from animal cells by intercalating drugs.

DNA polymerase gamma from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and chloroquine inhibition is less pronounced. In the case of DNA polymerases alpha and beta very little inhibition by ethidium bromide was observed. Intercalation of this dye in a poly dA-dT 12-18 template-primer was studied spectrophotometrically under conditions similar to those in the in vitro DNA polymerase assay. The polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase gamma activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT 12-18. We conclude that the drug, most probably in the intercalated form, is able to interact with the active site (s) of mitochondrial DNA polymerase.