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PubMed1987

Cerebral atrophy in younger persons: a comparative study between clinical examinations and computed tomography.

Eighty-nine patients, all below the age of 50 and under suspicion of dementia underwent computed tomography. The degree of cerebral atrophy was visually estimated and also calculated using different ventricular diameters and the mean width of four cortical sulci. The degree of dementia was evaluated by a neurological specialist. No correlation between internal atrophy and the degree of dementia was found. In spite of a significant correlation between external atrophy and the degree of dementia, there was such overlap and underestimation that the value of computed tomography in quantifying atrophy in younger persons is very limited. In none of the patients did computed tomography disclose any organic cause of dementia.

Adult↗

PubMed1997

Topographic distribution of seizure onset and hippocampal atrophy: relationship between MRI and depth EEG.

Medial temporal lobe epilepsy (MTLE) is associated with hippocampal cell loss and organization of the dentate gyrus. Some studies suggest a correlation between the topographic distribution of cell loss and site of epileptogenesis. We studied the relationship between the site of ictal onset with the presence of segmental atrophy in patients with non-lesional MTLE using magnetic resonance imaging (MRI) and depth EEG. Ictal recordings were obtained from 27 patients with longitudinal hippocampal depth electrodes and variable combinations of subdural strips sampling medial temporal structures. The location of the depth electrode contacts was correlated with anatomical landmarks. Seizures were analyzed for the distribution of onset along the long axis of the hippocampus. MRI analysis were performed to detect segmental atrophy. Outcome was assessed 1 year or more following anterior temporal lobectomy. Twenty-five patients had unilateral, and two had bilateral, hippocampal atrophy. One hundred and forty-seven seizures were reviewed: 21 showed focal onset and 126 showed regional onset. Ictal onset involved the amygdala and anterior half of the hippocampus in 80% of the seizures while only 40% of patients had atrophy of these segments. Most patients had excellent outcome. In patients with MTLE the primary area of epileptogenesis does not parallel the hippocampal segments with the greatest degree of volume loss.

Atrophy↗

PubMed2000

Reversible drug-induced oxyntic atrophy in rats.

BACKGROUND & AIMS: Oxyntic atrophy is the hallmark of chronic gastritis. Many studies have sought to develop animal models for oxyntic atrophy, but none of them are reversible. We now report that rats administered high doses of DMP 777 demonstrate reversible oxyntic atrophy. METHODS: DMP 777 was administered to CD-1 rats by oral gavage (200 mg. kg(-1). day(-1)). Serum gastrin level, in vivo acid secretion, and gastric histological changes were evaluated in DMP 777-dosed animals. Direct effects of DMP 777 on parietal cells were evaluated by assessment of aminopyrine accumulation into isolated rabbit parietal cells, as well as by assessment of DMP 777 effects on acridine orange fluorescence and H(+),K(+)-adenosine triphosphatase (ATPase) activity in isolated tubulovesicles. RESULTS: Oral dosing with DMP 777 caused a rapid increase in serum gastrin levels and severe hypochlorhydria. DMP 777 inhibited aminopyrine accumulation into rabbit parietal cells stimulated with either histamine or forskolin. DMP 777 reversed a stimulated proton gradient in isolated parietal cell tubulovesicles. Oral dosing with DMP 777 led to rapid loss of parietal cells from the gastric mucosa. In response to the acute loss of parietal cells, there was an increase in the activity of the progenitor zone along with rapid expansion of the foveolar cell compartment. DMP 777 treatment also led to the emergence of bromodeoxyuridine-labeled cells and cells positive for periodic acid-Schiff in the basal region of fundic glands. With extended dosing over 3-6 months, foveolar hyperplasia and oxyntic atrophy were sustained while chief cell, enterochromaffin-like cell, and somatostatin cell populations were decreased. No histological evidence of neoplastic transformation was observed with dosing up to 6 months. Withdrawal of the drug after 3 or 6 months of dosing led to complete restitution of the normal mucosal lineages within 3 months. CONCLUSIONS: DMP 777 acts as a protonophore with specificity for parietal cell acid-secretory membranes. DMP 777 in high doses leads to the specific loss of parietal cells. Foveolar hyperplasia, loss of normal gland lineages, and the emergence of basal mucous cells appear as sequelae of the absence of parietal cells. The results suggest that parietal cells are critical for the maintenance of the normal mucosal lineage repertoire.

Acridine Orange↗

PubMed1983

Evolution of renal segmental atrophy (Ask-Upmark kidney) in children with vesicoureteric reflux: radiographic and morphologic studies.

A radiographic and morphologic study of nine patients with renal segmental "hypoplasia," whose kidneys were radiographically normal when first examined, showed the lesion to be a form of localized, progressive renal atrophy. The renal abnormality bears a strong relationship to vesicoureteric reflux, which could be demonstrated in every patient. No evidence of renal scarring or atrophy was observed in initial roentgenographic examinations at a mean age of 2.9 years (range 0.1 to 10 years); however, serial studies during five to 14 years after discovery of vesicoureteral reflux demonstrated both a lack of renal growth and a progressive loss of substance irrespective of infection. Radiographic lengths of scarred kidneys, as measures of renal growth, correlated poorly with the radiographic surface areas of the renal parenchymal outlines. The mean time from discovery of vesicoureteric reflux to appearance of a renal scar was 6.1 years, and to onset of hypertension in six patients was 7.8 years. The renal abnormality consisted of lobar atrophy with variable tubular atrophy and glomerular sclerosis and with parenchymal destruction that in some specimens had proceeded to a complete loss of nephronic elements. The occasional presence of relatively well-preserved glomeruli and tubules and of focal segmental sclerosis within persisting glomeruli was taken as evidence of a progressive renal abnormality, as opposed to a static developmental hypoplasia. These observations indicate that renal scarring, the injury presumably having been initiated by vesicoureteric reflux, can progress despite correction of the reflux and despite prevention of urinary tract infection.

Adolescent↗

PubMed2003

Juvenile muscular atrophy of distal upper extremity associated with airway allergy: two cases successfully treated by plasma exchange.

Juvenile muscular atrophy of the distal upper extremity (JMADUE) is postulated to be a type of flexion myelopathy. However, patients with typical clinical features of JMADUE but without evidence of flexion myelopathy have been reported. We recently reported a significant association of JMADUE with airway allergy. Here we report the successful treatment by plasma exchange (PE) of two patients with both airway allergy and JMADUE without evidence of flexion myelopathy. Patient 1 had a 5-year history of allergic rhinitis and high titers of mite antigen-specific IgE, and patient 2 had an 8-year history of pollinosis and high titers of cedar pollen-specific IgE. Both patients noted progressive distal muscle atrophy and weakness of the upper extremities: patient 1 for 3 months and patient 2 for 3 years. Neurologically, both showed asymmetric intrinsic hand muscle atrophy, oblique atrophy of the forearm muscles, and weakness and contraction fasciculation (minipolymyoclonus) of these muscles without any sensory impairment. Neither had any evidence of flexion myelopathy on magnetic resonance imaging (MRI) in a flexed position. Both were subjected to PE three times. Soon after the PEs, both showed improvement of distal muscle weakness of the upper extremities and marked reduction of contraction fasciculation of the forearm muscles. Patient 1 showed marked reduction in ongoing denervation potentials in the distal muscles on needle electromyography, while patient 2 showed marked improvement of F wave persistence of bilateral median and ulnar nerves. Serum total and allergen-specific IgE decreased after PEs in both patients. PE was thus considered to be effective in these two patients having JMADUE without evidence of flexion myelopathy. These observations may suggest the involvement of an immune-mediated process in the neural damage of JMADUE without evidence of flexion myelopathy, especially in patients with atopic diathesis, and may support the notion that JMADUE is etiologically heterogeneous.

Adolescent↗

PubMed1998

Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee.

OBJECTIVE: To evaluate the efficacy of estrogen therapy in the treatment of postmenopausal women with symptoms and signs associated with urogenital atrophy, by meta-analysis of available data. METHODS: We searched the literature (Excerpta Medica, Biosis, MEDLINE, and hand search) for studies published between January 1969 and April 1995. Criteria for inclusion were English-language articles, peer-reviewed original publications, and urogenital atrophy assessed by at least one of the following outcomes: patient symptoms, physician report, pH, or cytologic change. Data had to allow comparison between treated and control groups in controlled trials or an estimated change from baseline in uncontrolled series. Meta-analytic methods were applied separately to controlled clinical trials and uncontrolled studies. RESULTS: Of the 77 relevant articles reviewed, nine contained ten randomized controlled trials. Meta-analysis of these using the Stouffer method revealed a statistically significant benefit of estrogen therapy for all outcomes studied. In 54 uncontrolled case series, the patient symptoms were treated by 24 different treatment modalities. All routes of administration appeared to be effective and maximum benefit was obtained between 1 and 3 months after the start of treatment. As expected, the least systemic absorption of estrogen was seen with estriol (administered orally or vaginally), then vaginal estradiol as measured by pretherapy and posttherapy serum estradiol and estrone. CONCLUSION: Estrogen is efficacious in the treatment of urogenital atrophy and low-dose vaginal estradiol preparations are as effective as systemic estrogen therapy in the treatment of urogenital atrophy in postmenopausal women.

Atrophy↗

PubMed2000

Cerebral atrophy in Cushing's disease.

BACKGROUND: Cushing's disease causes significant pathological changes throughout the body as a result of elevated cortisol levels. Very few systematic investigations have focused on the morphologic effects of hypercortisolism on the central nervous system. The validity of using premature cerebral atrophy as a diagnostic tool for Cushing's disease remains unknown. METHODS: This study includes 63 patients with Cushing's disease who were evaluated and treated at the University of Virginia Medical Center. Radiologists randomly compared these individuals with age- and sex-matched controls in a blinded protocol, assessing the degree of cerebral atrophy on computed tomography and magnetic resonance scans. RESULTS: Patients with Cushing's disease showed significant premature atrophy when compared with controls. This trend continued after subdividing the groups based on age and duration of symptoms except in the following groups: age greater than 60, duration of symptoms less than 1 year, and symptoms lasting between 4-5 years. CONCLUSIONS: Excluding the three aforementioned groups, the hypercortisolemic state manifested in patients with Cushing's disease promotes the premature development of cerebral atrophy, which can be identified on routine radiologic imaging and may assist in the clinical diagnosis of the condition.

Adult↗

PubMed2000

Role of interferon-alpha-2B in prevention of testicular atrophy with unilateral mumps orchitis.

OBJECTIVES: To determine the effectiveness of intravenously administered interferon-alpha-2B for the prevention of testicular atrophy in postpubertal men with mumps orchitis. METHODS: Eighteen patients with mumps orchitis were evaluated. The patients were hospitalized, and 3 x 1,000,000 IU intravenous interferon-alpha-2B was administered daily for a total of 7 days. All patients were evaluated by testicular biopsy on the 12th month after interferon treatment. RESULTS: Biopsy results demonstrated total atrophy of the seminiferous tubules in seven (38.8%), 10% atrophy in three (16.6%), and no apparent histopathologic alterations except an arrest in spermatogenesis in eight (44.6%) testes. CONCLUSIONS: Systematic treatment with interferon-alpha-2B does not seem completely effective in preventing testicular atrophy after mumps orchitis. Further investigations involving larger populations are needed.

Adolescent↗

PubMed1995

Proximal artificial sphincter cuff repositioning for urethral atrophy incontinence.

OBJECTIVES: Recurrent incontinence after implantation of an artificial urinary sphincter (AUS) may be due to urethral atrophy. Treatment options consist of decreasing the cuff size, increasing the balloon pressure, implanting a double-cuff system, or proximal cuff repositioning. The first three options may increase the risk of erosion. Increasing the balloon pressure does not effectively increase cuff pressure. This article demonstrates that proximal cuff repositioning is a safe, simple, and effective technique in the management of recurrent incontinence as a result of a loss of cuff compression due to urethral atrophy. METHODS: Six patients underwent proximal repositioning of the AUS (AS-800) cuff for recurrent post-prostatectomy incontinence. Urethral atrophy was determined by a thorough systematic evaluation. A detailed description of the surgical technique is provided. RESULTS: Five of 6 patients (83%) had significant improvement in incontinence with an average follow-up of greater than 1 year. In 1 patient with no improvement, preoperative urodynamics revealed poor detrusor compliance in addition to sphincter weakness due to loss of cuff compression. CONCLUSIONS: Proximal cuff repositioning on the bulbar urethra is an effective, safe, and simple technique in the management of recurrent incontinence due to urethral atrophy and may minimize the risk of erosion.

Aged↗

PubMed2004

Imaging cerebral atrophy: normal ageing to Alzheimer's disease.

CONTEXT: With ageing populations, the prevalence of dementia, especially Alzheimer's disease, is set to soar. Alzheimer's disease is associated with progressive cerebral atrophy, which can be seen on MRI with high resolution. Longitudinal MRI could track disease progression and detect neurodegenerative diseases earlier to allow prompt and specific treatment. Such use of MRI requires accurate understanding of how brain changes in normal ageing differ from those in dementia. STARTING POINT: Recently, Henry Rusinek and colleagues, in a 6-year longitudinal MRI study of initially healthy elderly subjects, showed that an increased rate of atrophy in the medial temporal lobe predicted future cognitive decline with a specificity of 91% and sensitivity of 89% (Radiology 2003; 229: 691-96). WHERE NEXT? As understanding of neurodegenerative diseases increases, specific disease-modifying treatments might become available. Serial MRI could help to determine the efficacy of such treatments, which would be expected to slow the rate of atrophy towards that of normal ageing, and might also detect the onset of neurodegeneration. The amount and pattern of excess atrophy might help to predict the underlying pathological process, allowing specific therapies to be started. As the precision of imaging improves, the ability to distinguish healthy ageing from degenerative dementia should improve.

Aged↗

PubMed1979

Abnormal intestinal permeability to sugars in villous atrophy.

Intestinal permeability to a monosaccharide and a disaccharide was compared by simultaneous measurement of the urinary excretion of L-rhamnose and lactulose after oral ingestion of an hypertonic solution containing both sugars. Urine samples were analysed for sugar content by quantitative thin-layer or paper chromatography. Results in thirteen patients with untreated villous atrophy were compared with those in twelve healthy volunteers. Urinary L-rhamnose excretion was significantly decreased (-40%, p less than 0.02) in patients with villous atrophy, whereas lactulose excretion was paradoxically and significantly increased (+345%, p less than 0.01). The median value of the lactulose/L-rhamnose urinary excretion ratio was sevenfold higher in the patients with villous atrophy; there was no overlap of values for patients and volunteers (p less than 0.01). It is postulated that reduced L-rhamnose urinary excretion in untreated villous atrophy is due to a decreased absorptive area in the small bowel, whereas increased lactulose excretion indicates leakiness of the abnormal mucosa to larger polar molecules.

Adult↗

PubMed1996

Visualisation and quantification of rates of atrophy in Alzheimer's disease.

BACKGROUND: Definitive diagnosis of Alzheimer's disease requires histological examination of brain tissue. In life, brain atrophy can be visualised by computed tomography or magnetic resonance (MR) imaging, but the atrophy due to the disease is difficult to distinguish from that caused by normal ageing. We have investigated use of accurate positional matching (registration) and digital subtraction of serially acquired MR brain scans to allow determination of rates of global and regional atrophy. METHODS: This technique was applied to eleven patients with clinically diagnosed Alzheimer's disease and eleven age-matched controls. Each individual had two scans approximately 1 year apart; scan intervals were matched between the groups. FINDINGS: The median rate of atrophy was significantly greater in the Alzheimer's disease group than in the control group (12.3 [range 5.8 to 23.6] vs 0.3 (-1.2 to 1.7) mL per year; p < 0.0001). There was no overlap between the groups. Furthermore, three non-demented individuals at risk of familial Alzheimer's disease had scans 6-14 months apart and showed greater rates of volume loss than the controls; these three individuals have subsequently developed symptoms. INTERPRETATION: This technique may be useful for the diagnosis of Alzheimer's disease, the assessment of disease progression, and the evaluation of potential treatments.

Alzheimer Disease↗

PubMed2003

Optic nerve atrophy in propionic acidemia.

OBJECTIVE: Propionic acidemia is a rare metabolic disorder that is diagnosed in the early neonatal period. The disorder is characterized by life-threatening ketoacidosis, lethargy, failure to thrive, and developmental delay. Herein we report the ocular findings in a prospective series of six patients with propionic acidemia. DESIGN: Prospective case series. PARTICIPANTS: Six children (three male and three female) between the ages of 2 and 10 years with propionic acidemia who were examined at Children's Hospital Los Angeles. METHODS: A complete ophthalmic examination was performed on each of the six children. The examination included visual acuity testing, ocular motility, anterior segment examination, and funduscopic evaluation. Emphasis was placed on the function of the optic nerve and on the appearance of the optic disc, looking for possible atrophic changes. MAIN OUTCOME MEASURES: The clinical appearance of the optic disc and evidence of optic neuropathy. RESULTS: Optic nerve atrophy was present exclusively in all of the male patients in the series; none of the female patients demonstrated any detectable impairment of optic nerve function. The optic nerve atrophy was symmetric and age dependent and varied from moderate to severe. There were no other anterior or posterior segment abnormalities, other than one case of unilateral morning glory syndrome, diagnosed at birth. There was no correlation between metabolic control and the development and progression of optic nerve atrophy. CONCLUSIONS: Males with propionic acidemia have moderate to severe bilateral optic atrophy.

Amino Acid Metabolism, Inborn Errors↗

PubMed1984

Narrowing of the retinal arterioles in descending optic atrophy. A quantitative clinical study.

Measurements were made on fundus photographs of the diameters of retinal arterioles in a series of cases with various nonvascular lesions of the anterior visual pathways, before and after the development of fundus signs of optic atrophy. A simple method was devised for reliable estimation of the diameter of the central retinal artery whenever this vessel could not be measured directly: this allowed comparisons to be made between different eyes, irrespective of individual variations in arteriolar branching patterns. Atrophy was consistently associated with a decrease in central retinal artery caliber, averaging 24% in eyes developing total optic atrophy, and 17% in eyes with hemi-atrophy. Normal controls showed a maximum side difference of 8%.

Adolescent↗

PubMed1990

Optic nerve head swelling and optic atrophy in the systemic mucopolysaccharidoses.

The ocular findings in 108 patients representative of all types of mucopolysaccharidoses (MPS) were reviewed. Attention was focused on optic nerve head appearance. Optic nerve head swelling was observed in 8/14 eyes of MPS 1-Hurler (MPS 1-H); 9/21 MPS 1-Hurler-Scheie (MPS 1-H-S); 0/4 MPS I-S; 13/66 MPS II; 1/22 MPS III; 0/58 MPS IV; 5/12 MPS VI; and 2/2 MPS VII eyes. In three patients, optic nerve head swelling was present in one eye and optic atrophy in the fellow eye; in four patients, optic atrophy followed disc elevation; three patients presented with bilateral optic atrophy. It was concluded that optic nerve head swelling precedes the development of optic atrophy in the systemic MPS.

Adolescent↗

PubMed1997

The associations of optic disc hemorrhage with retinal nerve fiber layer defect and peripapillary atrophy in normal-tension glaucoma.

OBJECTIVE: The purpose of the study is to elucidate a topographic correlation between optic disc hemorrhages and retinal nerve fiber layer defects as well as peripapillary atrophy in normal-tension glaucoma (NTG). DESIGN: The authors prospectively studied the relation between the precise locations of disc hemorrhages and retinal nerve fiber layer defects in the first part of the study. The authors also compared morphometrically the peripapillary atrophy and the optic disc in eyes with disc hemorrhage with eyes without a history of disc hemorrhage in age-matched patients in the second part of the study. PARTICIPANTS: In part 1, 42 patients with NTG (male/female = 11/31; age, 56.8 +/- 14.2 years) in whom new disc hemorrhages developed were enrolled. In part 2, 51 randomly selected age-matched patients with NTG without a history of disc hemorrhage (male/female = 16/35; age, 55.7 +/- 12.5) were examined. MAIN OUTCOME MEASURE: In part 1, retinal nerve fiber layer defects were observed by scanning laser ophthalmoscopy using an argon-blue laser. In part 2, the area, angular extent, and radial extent of zone beta of peripapillary atrophy and the structural parameters of optic disc were measured by scanning laser tomography using a diode laser. RESULTS: In part 1, the authors detected 64 disc hemorrhages in 48 eyes of 42 patients; retinal nerve fiber layer defects were shown in 47 (97.9%) of 48 eyes by scanning laser ophthalmoscopy. Of 64 disc hemorrhages, 51 (79.7%) coincided with retinal nerve fiber layer defects in location. These 51 hemorrhages were present on the border (41.2%) or adjacent to the border (58.8%) between the retinal nerve fiber layer defect and the apparently healthy-looking retinal nerve fiber layer. In part 2, the prevalence, area, angular extent of zone beta, and ratio of zone beta area to disc area were significantly greater in the disc hemorrhage group than in the nonhemorrhage group, even though there were no significant differences in disc parameters between the two groups. CONCLUSIONS: Disc hemorrhage is associated closely with retinal nerve fiber layer defect in location and the size of peripapillary atrophy in NTG.

Adult↗

PubMed1990

Blood flow in the atrophied pancreas.

Pancreatic and islet blood flow was measured by quantitative determination of microspheres within atrophied pancreases of rats rendered dietarily copper-deficient. The deficient state effects selective acinar necrosis and its replacement with non-inflammatory lipomatosis. While blood flow to lipomatous glands remained intact, it was significantly less (0.41 +/- 0.02 ml/min X g pancreas) compared to normal control glands (0.50 +/- 0.01 ml/min X g pancreas). Blood flow to islets, which remain unaffected by selective acinar atrophy of the copper-deficient state, was not significantly altered (50.8 +/- 2.13 microliters/min X g pancreas) compared to controls (55.7 +/- 2.66 microliters/min X g pancreas). The percent of islet blood flow (IBF) within atrophied glands (12.2 +/- 0.31) was found to be significantly greater than control glands (10.7 +/- 0.21). It is suggested that the maintenance of IBF and IBF percentage in the atrophic pancreas may reflect the parallel arrangement of islet angioarchitecture which based on morphological data is not appreciably altered with attenuation of acinar plexuses. Microspheres, although not quantitated, were also found distributed within the adventitia of ducts as well as in vessels supplying intrapancreatic nerves and ganglia which remain intact in copper deficiency-induced acinar atrophy.

Animals↗

PubMed1997

Apolipoprotein E e4 allele frequency in patients with multiple system atrophy.

The glial cytoplasmic inclusion provides a histological hallmark for multiple system atrophy, a group of neurodegenerative disorders including: striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome. Apolipoprotein E (APOE) genotype was determined by the polymerase chain reaction and restriction digestion of DNA extracted from frozen brain tissue from 22 patients (64.9 +/- 2.2 years) with clinically and neuropathologically verified multiple system atrophy (MSA). In addition, brain tissue from 36 age- and sex-matched patients who died with Alzheimer's disease (68.8 +/- 1.6 years) and 66 neurologically and psychiatrically normal subjects (66.6 +/- 1.8 years) was genotyped. The APOE e4 allele frequency in the Alzheimer's disease subjects was significantly increased (0.44, P < 0.001), as has been reported previously. The APOE e4 allele frequency of the MSA cases (0.11) was not significantly different from that of the control subjects (0.12). These data indicate that the APOE e4 allele is not a risk factor for multiple system atrophy.

Aged↗