Course and prognosis of chronic progressive multiple sclerosis: Results of an epidemiological study

In studies on the natural course of multiple sclerosis (MS), several forms of the disease are distinguished. The most important are the relapsing remitting and the chronic progressive forms. The relationship between these remains unclear. In a prospective epidemiological survey we studied the course of MS using the year in which the chronic-progressive phase started as a landmark. The reliability of this "year of progression" was examined in an observer agreement study. Data were acquired from 342 patients. Progression of the handicap was most rapid in case of a secondary progressive course, female sex, high relapse rate in the preceding remitting phase and "year of progression" at a higher age. Survival after the "year of progression" was lowest in the secondary progressive group. Determining the "year of progression" seems to be significant for the prognosis.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Development of spinocerebellar afferents in the clawed toad, Xenopus laevis

The development of spinocerebellar projections in the clawed toad, Xenopus laevis, was studied with horseradish peroxidase as an anterograde and retrograde tracer. Early in development cells of origin of spinocerebellar projections were found, contralaterally, in or close to the medial motor column. In older tadpoles ipsilaterally projecting spinal neurons were also labeled from the cerebellum. These are virtually indistinguishable from the large primary motoneurons that occupy a very similar position in the spinal cord. Most of the labeled spinal cells were found in the thoracic spinal cord; they lie halfway between the brachial and lumbar secondary motor columns. Surprisingly, no primary spinocerebellar projection arising from dorsal root spinal ganglion cells could be demonstrated in X. laevis tadpoles and adult toads. Therefore, fibers in the cerebellum that were labeled anterogradely from the spinal cord can be expected to originate exclusively from the secondary spinocerebellar tract cells. These fibers appear to cross the cerebellum in or at the border of the granular layer. The present data suggest that in X. laevis early in the development of the cerebellum a distinct secondary spinocerebellar projection is already present, originating in neurons that can be compared with the "spinal border cells" in mammals. The relative sparseness of this secondary spinocerebellar projection and the apparent absence of primary spinocerebellar afferents probably indicate that spinocerebellar pathways are only of minor importance in X. laevis. The possibility remains, however, that the expansion of the secondary spinocerebellar pathway only starts when metamorphosis has been completed.     

Delirium in liver transplantation candidates: discriminant analysis of multiple test variables

We report the results of electroencephalograms, Mini-Mental State exam, Trailmaking Tests A and B, and serum albumin levels in 108 consecutive liver transplantation candidates. We compared test results to a clinical DSM-III diagnosis of delirium. Although each variable could differentiate between the two groups (delirium n = 18; nondelirium n = 90) at a statistically significant level, a discriminant analysis involving either all variables or only three particular variables (Trailmaking B, EEG code, and albumin) resulted in the highest specificity (97.8%) and sensitivity (83.3%), with a correct classification of 95.4% of subjects. The analysis also generates an equation that can be applied to clinical situations to enhance the accurate recognition of delirium. In addition, to explain abnormal Trailmaking B scores and/or EEGs in subjects who did not otherwise meet DSM-III criteria for delirium, we suggest the presence of a "subclinical delirium."     

Central nervous system involvement in early and late syphilis: the problem of asymptomatic neurosyphilis

Patients with syphilitic infections are at risk of development of symptomatic neurosyphilis. Adequate treatment with 2.4-7.2 x 10(6) units benzyl penicillin-G intramuscularly within 1 year after infection will rule out this risk. However, more than 1 year after infection this treatment is not fully reliable. In asymptomatic CNS involvement (asymptomatic neurosyphilis) only intravenous penicillin treatment is considered to be adequate in the prevention of neurosyphilis. In this study we redefined criteria for this condition by comparing serum and cerebrospinal fluid (CSF) samples of symptomatic neurosyphilitic patients with those of latent syphilitic patients without CNS involvement. Diagnostic criteria of the World Health Organization and of Centers of Disease Control for asymptomatic neurosyphilis (positive CSF Venereal Disease Research Laboratory (VDRL) test, combined with raised CSF cell count and/or protein content) were studied and compared with some newer parameters such as signs of intrathecal treponemal antibody production (Treponema pallidum haemagglutination assay and intrathecal Treponema pallidum assay index), immunoglobulin G (IgG) and M (IgM) index. The results of this study in 203 syphilitic patients revealed that either a positive CSF-VDRL or combination of a raised IgG and/or IgM index with an elevated CSF cell count both are useful criteria for "ruling-in" asymptomatic neurosyphilis.     

Increased suicidality in depression: group or subgroup characteristic?

A lifetime history of depressive episodes and suicide attempts was ascertained from 172 depressed patients admitted to a psychiatric inpatient service. Fifty-five of these patients had made at least one suicide attempt. The correlation of depressive episodes and the total number of suicide attempts for this group was close to zero. However, when the data were converted into rate measures (number of episodes or attempts per year), the correlations were very high and significant. It appears that approximately one-third of severely depressed, hospitalized patients have a history of suicide attempts and, once a suicide attempt has occurred, the patient is at high risk for more suicide attempts if future depressions occur. Within the group of depressives with a history of suicide attempt, the risk of suicidal behavior is evenly distributed. No evidence in favor of a "hypervulnerable" subgroup was found.     

Adult polyglucosan body myopathy with subclinical peripheral neuropathy: case report and review of diseases associated with polyglucosan body accumulation

A 65-year-old female had polyglucosan body myopathy, usually called "polysaccharide storage myopathy" that presented with increasing distal paresis and only slight weakness of the proximal limb girdle musculature. Muscle biopsy revealed dystrophic changes that could have been mistaken for muscular dystrophy, and the characteristic light as well as electron microscopic features of polyglucosan bodies varying in number at the three sites of muscle biopsies studied (deltoid, quadriceps femoris, and anterior tibial muscle). In addition, there were occasional nonspecific paracristalline mitochondrial inclusions. No abnormal polyglucosan deposits were found in the sural nerve biopsy. Morphometric evaluation of nerve fiber cross sectional areas revealed some degree of demyelination and remyelination, and of nerve fiber degeneration and regeneration. Unlike a series of 10 unselected control sural nerves with Renaut bodies, hypomyelinated nerve fibers were more numerous adjacent to Renaut bodies. This is the first case of polyglucosan body myopathy in which the axon/myelin ratio and the axonal circularity factor in the sural nerve is evaluated and in which a definite lack of polyglucosan bodies or other abnormal glycogen storage products in a peripheral nerve is documented.     

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery

In this study, 417 patients undergoing "clean" elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis--a statistically significant difference (p less than 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.     

Phenotyping of acute myelocytic leukemia (AML) progenitors: an approach for tracing minimal numbers of AML cells among normal bone marrow

Previous studies have shown that the phenotypes of progenitors of human AML (AML-CFU) are variable, reflecting arrests at different stages of maturation. We were interested to seek discrepancies between the surface properties of AML precursors and normal bone marrow colony formers in order to detect minimal numbers of AML cells among normal bone marrow cells in remission bone marrow. Therefore, we selected two surface markers, the MoAb CD34, reactive with blast cells, and Vim-2, a surface marker reactive with mature myeloid cells, and determined the antigen density of these markers (relative fluorescence intensity using fluorescence-activated cell sorting) for normal marrow and AML progenitors. While these markers defined an identical phenotype (CD34++/Vim-2-/+) for a broad spectrum of normal progenitors, i.e., CFU-GEMM, BFU-e, day 15 CFU-GM, and day 7 CFU-GM, referred to as the "normal" progenitor phenotype, AML progenitors frequently exhibited different phenotypes. In 12 of 20 cases the phenotypes of the majority of AML progenitors were discrepant from the normal surface profile, i.e., according to one marker in 8 cases (CD34-/+/Vim-2-/+ or CD34++/Vim-2++) and two markers in 4 cases (CD34-/+/Vim-2++). Since these data indicate that AML and normal progenitors were frequently distinguishable, we then determined the potential utility of these phenotypic dissimilarities for detection of minimal disease. Artificial mixtures of normal bone marrow and minimal numbers (0.1-1%) of AML cells were prepared. Based upon the phenotypic discrepancies, AML metaphases were successfully demonstrated in these mixtures following cell sorting and culture. Thus, it appears that minimal numbers of AML mitoses can be identified with an approximate 10(-2) to 10(-3) sensitivity by taking advantage of differential coexpression of surface antigens.     

Pattern electroretinogram can be more than the sum of local luminance responses

It is generally accepted that the pattern electroretinogram for very large spatial elements is the result of local luminance stimulation. Responses due to the luminance differences between elements may be assumed to be relatively unimportant because in the case of large elements only few retinal units are stimulated by gradients. With decreasing pattern element size one wonders to what extent the electroretinogram continues to be based on the local luminance stimulation. We investigated this question using 8 Hz checkerboard reversal and compared the pattern recordings with the recordings resulting from the same stimulus field modulated homogeneously (focal electroretinogram). A 100% modulated checkerboard at retinal level may be considerably less modulated because of imperfect optics of the eye. So the pattern electroretinogram should be compared with homogeneous field stimulation of correspondingly lower modulation depth. On the basis of the optical transfer properties of the eye we compared by subtracting the proper focal electroretinogram from the pattern electroretinogram. The difference response was virtually zero for check sizes larger than 120. For checks from 60 down the difference response was of the same order of magnitude as the adjusted focal recording. This difference response for eyes with normal optics is largest around 30; its wave form was found to be rather invariant with check size.