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Biomedical subjects

D A Katz

Publications and source records attributed to D A Katz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Successful reversal of acute vascular rejection in a renal allograft with combined mycophenolate mofetil and tacrolimus as primary immunotherapy.

Despite the use of newer immunosuppressive drugs, early allograft rejection is still a major cause of graft loss and diminished graft survival. The pathological picture of acute interstitial rejection usually responds to high dose steroids, whereas the treatment of acute vascular (AVR) rejection characterized by an intense vasculitis and/or endotheliolitis is more formidable. The use of newer monoclonal antibodies specific for T lymphocytes and their subsets has only been occasionally successful in reversing AVR. Here we report a case of successful reversal of acute vascular renal allograft rejection with mycophenolate mofetil (MMF) and tacrolimus as primary therapy.

Adult↗
PubMed1996

The use of empiric clinical data in the evaluation of practice guidelines for unstable angina.

OBJECTIVE: To determine the applicability to emergency department (ED) clinical practice of a nationally disseminated practice guideline on the disposition of patients with a diagnosis of unstable angina, and to determine the potential impact of the guideline on hospital admissions and demand for intensive care beds. DESIGN: Application of guideline criteria for ED disposition decisions to a validation sample derived from a prospective clinical trial. SETTING: Five hospitals, including 2 urban general teaching hospitals, 2 urban tertiary care university hospitals, and 1 suburban university-affiliated community hospital. PATIENTS: A consecutive sample of 457 patients who presented with symptoms suggestive of acute cardiac ischemia and who had "unstable angina" or "rule out unstable angina" diagnosed by ED physicians. Greater than 90% of eligible patients were enrolled in the clinical trial; follow-up data sufficient for assignment of a definitive diagnosis were obtained for 99% of subjects. MAIN OUTCOME MEASURES: Acute myocardial infarction and unstable angina, based on blind review of initial and follow-up clinical data, including cardiac enzyme levels and electrocardiograms. After completion of the trial, without knowledge of final diagnosis or outcome, the investigators classified patients into risk groups specified by the unstable angina guideline. RESULTS: Of subjects with an ED diagnosis of unstable angina, only 6% (n=28) met the guideline's criteria corresponding to low risk for adverse events and were therefore suitable for discharge directly to home. Fifty-four percent (n=247) met the intermediate-risk criteria; 40% (n=182) met the high-risk criteria and were identified as requiring admission to an intensive care unit. Actual ED disposition differed from guideline recommendations in 2 major areas: only 4% (1/28) of low-risk patients were discharged to home with outpatient follow-up, and only 40% (72/182) of high-risk patients were admitted to an intensive care unit. CONCLUSIONS: Although the guideline was intended to reduce hospitalization by identifying a low-risk group, the small size of this group among ED patients suggests that little reduction in hospitalization can be expected. Indeed, the guideline may increase demand for the limited number of intensive care beds to accommodate patients with unstable angina considered high-risk but currently placed elsewhere. These results emphasize the need to use empiric data from target clinical settings to assess the likely actual impact of guidelines on clinical care prior to national dissemination.

Angina, Unstable↗
PubMed1996

Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea.

BACKGROUND: Although routine testing of hospitalized patients with diarrhea for Clostridium difficile cytotoxin has been advocated as a high-yield procedure, the rationale for this practice has been questioned. To target a low-yield subgroup for whom routine testing could be deferred, we derived a clinical decision rule for predicting results of the C difficile cytotoxin assay in hospitalized adults with diarrhea. METHODS: We hypothesized a priori that two variables, antibiotic use (within 30 days prior to testing) and history of significant diarrhea (new onset of > 3 partially formed or watery stools per 24 hour period), would be highly predictive of cytotoxin results, and obtained these data on 480 consecutive patients who underwent diagnostic testing for C difficile at a university hospital and affiliated Veterans Affairs medical center. For more detailed modelling, we recorded symptoms, signs, comorbidity, and other potential causes of diarrhea for 68 test positive patients (cases) and 265 randomly selected test negative patients (controls) within the study cohort. RESULTS: The overall prevalence of positive cytotoxin assays was 14%. Prior antibiotic therapy (OR = 9.0, 95% CI 2.1-38.4), significant diarrhea (OR = 2.2, 95% CI 1.1-4.7), and abdominal pain (OR = 1.9, 95% CI 0.96-3.7) were independent predictors of cytotoxin assay results. The model discriminated patients with positive and negative assays with a receiver operating characteristic (ROC) area of 0.68; observed and predicted probabilities of a positive cytotoxin assay were well correlated over the entire range of observed probabilities (r2 = 0.86). A decision rule (defined as positive if prior antibiotic use and either significant diarrhea or abdominal pain are present) demonstrated sensitivity and specificity of 86 and 45%. When applied to the entire dataset (N = 480), a simplified a priori rule, defined as positive if both prior antibiotic use and history of significant diarrhea are present, demonstrated sensitivity, specificity, positive and negative predictive value of 80, 45, 18 and 94%, respectively (6% of those predicted to be cytotoxin-negative actually tested positive). Use of this rule would have averted 39% of cytotoxin assays in our study population. CONCLUSIONS: Patients without prior antibiotic use and either significant diarrhea or abdominal pain are unlikely to have positive C difficile cytotoxin assay results, and may not routinely require cytotoxin testing.

Abdominal Pain↗
PubMed1996

Two 21-kilodalton components of the Epstein-Barr virus capsid antigen complex and their relationship to ZEBRA-associated protein p21 (ZAP21).

The viral capsid antigen complex of Epstein-Barr virus (EBV), an important serodiagnostic marker of infection with the virus, consists of at least four components, with molecular masses of 150, 110, 40, and 21 kDa. Here we show that the 21-kDa component of the viral capsid antigen consists of products of two EBV genes, BFRF3 and BLRF2. Both products were expressed from late transcripts, were recognized by human antisera, and were present in virions. The BFRF3 product, but not that of BLRF2, fulfilled the definition of ZEBRA-associated protein p21 (ZAP21). In cells in which EBV was lytically replicating, BFRF3 protein was coimmunoprecipitated together with ZEBRA by a rabbit antiserum directed against amino acids 197 to 245 of BZLF1. In EBV-negative cells cotransfected with BZLF1 and BFRF3 expression vectors, BFRF3 was also coimmunoprecipitated with this antiserum. Although this antiserum could not detect BFRF3 on an immunoblot, it was able to immunoprecipitate BFRF3 in the absence of ZEBRA expression. The rabbit antiserum to amino acids 197 to 245 of BZLF1 was found to detect the same epitope at the carboxy end of BFRF3 as was recognized by rabbit antiserum to BFRF3 itself. Thus, coimmunoprecipitation of BFRF3 p21 with ZEBRA appeared to be due to cross-reactivity of the immunoprecipitating antiserum rather than to direct association of ZEBRA and BFRF3 p21.

Animals↗
PubMed1996

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

OBJECTIVES: To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS: Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS: Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS: Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.

Aged↗
PubMed1996

Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene.

Nelson's syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing's disease. Extremely high plasma ACTH levels and aggressive neoplastic growth might be explained by the lack of appropriate glucocorticoid negative feedback due to defective glucocorticoid signal transduction. To study the glucocorticoid receptor (GR) gene in Nelson's syndrome, DNA was extracted from pituitary adenomas and leukocytes of four patients with this condition and amplified by PCR for direct sequence analysis. In one of the tumors, a heterozygous mutation, consisting of an insertion of a thymine between complementary DNA nucleotides 1188 and 1189, was found in exon 2. This frame-shift mutation led to premature termination at amino acid residue 366 of the wild-type coding sequence, excluding the expression of a functioning receptor protein from the defective allele. The mutation was not detected in the sequence of the GR gene in the patient's leukocyte DNA, indicating a somatic origin. By lowering the receptor number in tumorous cells, this defect might have caused local resistance to negative glucocorticoid feedback similar to that caused by the presence of a null allele in a kindred with the generalized glucocorticoid resistance syndrome. P53 protein accumulation, previously reported in 60% of corticotropinomas, could not be detected in any of the four pituitary tumors examined by immunohistochemistry. We suggest that a somatic GR defect might have played a pathophysiological role in the tumorigenesis of the corticotropinoma bearing this mutation.

Adrenocorticotropic Hormone↗
PubMed1996

Cushing's disease preceded by generalized glucocorticoid resistance: clinical consequences of a novel, dominant-negative glucocorticoid receptor mutation.

Generalized glucocorticoid resistance is associated with chronic hyperactivation of the hypothalamic-pituitary-adrenal axis, compensating for impaired glucocorticoid receptor function. We report a unique patient with sporadic generalized glucocorticoid resistance who, at age 33, presented with infertility and hypertension and, at 38, developed pituitary Cushing's disease. Leukocyte-binding studies revealed normal affinity of the glucocorticoid receptor but a reduction of binding sites by 50%. [3H]thymidine incorporation by this patient's lymphocytes was not suppressible by dexamethasone. He had a novel heterozygous missense mutation in the glucocorticoid receptor gene (isoleucine 559 to asparagine 559). The mutant receptor exhibited a strong dominant-negative effect on the ability of the wild-type receptor to induce gene transcription in vitro. The mutation was present in all of the patient's cultured lymphoblasts and fibroblasts as well as in 50% of his sperm, as demonstrated by single-cell polymerase chain reaction; it was not present in his parents and seven siblings. This novel mutation was thus both de novo and present in the germ line. Immunohistochemical staining of this patient's pituitary corticotropinoma revealed accumulation of p53 protein, indicating the presence of a putative somatic oncogenic mutation in the p53 gene in the tumor cells. Investigation of the lymphoblast and skin fibroblast cultures for p53 abnormalities did not show any aberration. Thus, a novel de novo germ line mutation of the glucocorticoid receptor with strong dominant-negative activity caused severe sporadic generalized glucocorticoid resistance, which preceded corticotroph adenoma formation. The latter probably was due to the combined effects of chronic corticotroph hyperstimulation, decreased glucocorticoid negative feedback, and at least one subsequent somatic defect in the control of the cell cycle.

Adult↗
PubMed1995

Fc gamma RII, Fc gamma RIII, and CD18 receptors mediate in part neutrophil activation on a plasma coated expanded polytetrafluoroethylene surface.

BACKGROUND: A biomaterial-induced polymorphonuclear neutrophil (PMN) defect may predispose the implanted vascular graft to infection. PMNs bind, activate, and undergo morphologic changes when exposed to uncoated or plasma coated expanded polytetrafluoroethylene (ePTFE) surfaces. The purpose of this study was to investigate whether the CD18 integrin receptor or the immunoglobulin receptors Fc gamma RII and Fc gamma RIII mediate either PMN binding or activation on ePTFE. METHODS: PMN binding and activation were determined after incubation of these cells on human immunoglobulin (IgG) or fibrinogen coated surfaces and uncoated or plasma coated ePTFE. PMN activation was measured by using the ferricytochrome reduction assay. Binding was determined with chromium 51-labeled PMNs. To block the Fc gamma RII, Fc gamma RIII, and CD18 receptors, PMNs were preincubated with the monoclonal antibodies (mAbs) IV.3, 3G8, and IB4, respectively. Irrelevant isotype matched mAbs were used as control. RESULTS: Monoclonal antibody IB4 inhibited binding of activated PMNs to fibrinogen coated surfaces. Binding to IgG was affected by either mAb IB4 or IV.3, but the greatest degree of inhibition was achieved when mAbs IB4 and IV.3 were used in combination. IgG-induced activation was partially inhibited by mAb IV.3 but was fully inhibited by a combination of mAbs IB4 and IV.3 The mAbs did not affect PMN binding to uncoated or plasma coated ePTFE, nor was PMN activation on the uncoated ePTFE surface inhibited. PMN activation on the plasma coated ePTFE surface was, however, partially inhibited by the combination of mAb IB4 with either mAb IV.3 or 3G8. CONCLUSIONS: A synergistic interaction between the PMN Fc gamma RII receptor and the CD18 integrin receptor accounts for surface bound IgG-induced cell activation. Both receptors also play a role in mediating PMN activation on the plasma-coated ePTFE surface.

Antibodies, Monoclonal↗
PubMed1995

Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

AIDS Dementia Complex↗
PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗
PubMed1995

Circle of Willis: evaluation with spiral CT angiography, MR angiography, and conventional angiography.

PURPOSE: To evaluate the use of spiral computed tomographic (CT) angiography in the analysis of the arteries of the circle of Willis and compare these results with magnetic resonance (MR) angiography and conventional angiography. MATERIALS AND METHODS: The results in 17 patients who underwent examination were prospectively studied in a blinded fashion. The presence or absence of the arteries of the circle of Willis was determined by using maximum intensity projection reconstructions from CT angiography and MR angiography. These results were compared with results from conventional angiography. RESULTS: Similar sensitivities were determined for CT angiography (88.5%) and MR angiography (85.5%); however, MR angiography was found to differ significantly (P = .005) from conventional angiography. No significant differences (P > .05) were found between the two modalities and conventional angiography in the detection of the anterior, middle, or posterior cerebral arteries or the anterior communicating artery. CONCLUSION: Spiral CT angiography is highly sensitive in the detection of arterial anatomy in the circle of Willis and is a reliable alternative to MR angiography.

Cerebral Angiography↗
PubMed1995

Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings.

PURPOSE: To evaluate and describe the neuroimaging findings of patients with neurosyphilis. METHODS: The neuroimaging studies of 35 patients with documented neurosyphilis were reviewed. Diagnosis was established in 34 patients with cerebrospinal fluid for a Venereal Disease Research Laboratory test, complemented by autopsy in 1 and brain biopsy in 1. All patients had reactive fluorescent treponemal antibody tests with absorption in their sera. Imaging studies included plain and contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, MR angiography, and conventional angiography. Imaging findings were also correlated with the relevant pathologic findings at autopsy in three additional patients with neurosyphilis who did not have brain imaging studies. RESULTS: Of the 35 patients with imaging studies, 32 tested human immunodeficiency virus (HIV)-seropositive, and 3 were HIV-seronegative. Eleven (31%) of 35 patients had normal radiographic findings. Cerebral infarctions were seen in 8 (23%) of 35 patients, and nonspecific white matter lesions in 7 (20%) of 35. Cerebral gummas and extraaxial enhancement indicating meningitis were noted in 2 (6%) of 35 patients, respectively. Arteritis was demonstrated in 2 (50%) of 4 patients who underwent either MR angiography or conventional angiography. The 3 subjects who had autopsy but not imaging studies were found to have manifestations of meningovascular syphilis, including syphilitic leptomeningitis and an obliterative endarteritis. CONCLUSION: We conclude that findings of vascular occlusive disease manifested as infarction or arteritis, enhancing cortical lesions with or without adjacent meningeal enhancement, focal or diffuse extraaxial enhancement, and white matter disease, although nonspecific, in the proper clinical setting should prompt appropriate testing for neurosyphilis, a treatable disease, in patients with and without HIV infection.

AIDS Dementia Complex↗
PubMed1994

AU-A, an RNA-binding activity distinct from hnRNP A1, is selective for AUUUA repeats and shuttles between the nucleus and the cytoplasm.

The 3'-untranslated regions of many labile transcripts contain AU-rich sequences that serve as cis determinants of mRNA stability and translational efficiency. Using a photocrosslinking technique, our laboratory has previously defined three cytoplasmic RNA-binding activities specific for the AUUUA multimers found in the 3'-untranslated regions of lymphokine mRNAs. One of these activities, AU-A, has an apparent molecular mass of 34 kDa, is constitutively expressed in both primary T cells and the Jurkat T cell leukemia line, and binds to a variety of U-rich RNA sequences. Previous studies had shown that AU-A is more prevalent in the nucleus than the cytoplasm, raising the possibility that AU-A is really a nuclear RNA-binding activity that is found in cytoplasmic extracts because of nuclear leakage during cell fractionation. We now show that AU-A shuttles between the cytoplasm and the nucleus. Our results indicate that AU-A is a candidate protein component of ribonucleoprotein complexes that participate in nucleocytoplasmic transport of mRNA and cytoplasmic mRNA metabolism. The properties of AU-A activity are similar to those of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). However, using monoclonal antibodies to hnRNP A1 and protease digestion patterns, we show that AU-A activity and hnRNP A1 protein are distinct. These studies have also allowed us to define a fourth RNA-binding activity of apparent molecular mass 41 kDa with specificity for AUUUA multimers. This activity is restricted to the nucleus and contains the hnRNP C protein.

Base Sequence↗
PubMed1994

Progressive multifocal leukoencephalopathy complicating Wiskott-Aldrich syndrome. Report of a case and review of the literature of progressive multifocal leukoencephalopathy with other inherited immunodeficiency states.

OBJECTIVE: To describe the occurrence of progressive multifocal leukoencephalopathy (PML) in association with Wiskott-Aldrich syndrome, an X-linked recessive disorder with impairment of both cellular and humoral immunity. DESIGN: A detailed analysis of this patient's clinical illness, immunologic factors, neuroradiographic findings, and brain histopathologic conditions was undertaken. The medical literature on PML complicating congenital immunodeficient states was also reviewed. SETTING: A 1500-bed, university-affiliated, public health hospital. PATIENT: A 15-year-old boy with Wiskott-Aldrich syndrome. His neurologic illness was heralded by dysarthria and right-sided weakness and the diagnosis was established by brain biopsy specimen. Survival from the time of onset of PML was 10 months. CONCLUSION: Although PML typically occurs in the setting of severe acquired cellular immunodeficiency, often as a consequence of acquired immunodeficiency syndrome, organ transplantation, and leukemia and lymphoma, it may rarely accompany inherited immunodeficiency syndromes. The reported childhood cases of PML include three patients, aged 5, 11, and 18 years, with other inherited immunodeficiency syndromes. This patient represents the first time (to our knowledge) that PML has been reported to occur in association with Wiskott-Aldrich syndrome.

Adolescent↗
PubMed1994

Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.

OBJECTIVE: To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy. PATIENTS: Five symptomatic and nine asymptomatic at-risk members of the kindred. INTERVENTIONS: Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy. RESULTS: Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symptoms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology. CONCLUSION: This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown.

Chronic Disease↗
PubMed1994

Childhood ataxia with diffuse central nervous system hypomyelination.

A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.

Ataxia↗