Atrophy Subtypes Research Articles

Comparison of magnetic resonance imaging in subtypes of multiple system atrophy

Some abnormal findings in routine MRI have been proposed as helpful discriminators for distinguishing multiple system atrophy (MSA) from Parkinson's disease (PD). However, what the most distinguishing MRI findings for MSA-p (parkinsonism dominant) or MSA-c (cerebellar dominant) are separately has not been systematically analyzed. To determine what the most helpful discriminators for MSA-p or MSA-c are and whether those findings are correlated with the presence of parkinsonism or cerebellar dysfunction, we compared 10 previously reported MRI findings in 36 patients with probable MSA-p, 27 patients with probable MSA-c and 30 patients with PD separately. In our results, hyperintense rim and putaminal atrophy among supratentorial parameters and the parameters of infratentorial atrophy were significantly prominent in MSA-p comparing to PD. Hyperintense rim showed the highest specificity in MSA-p patients (90.0%) with relatively suboptimal sensitivity (72.2%). In MSA-c, all infratentorial parameters had strong discriminating power comparing to PD. Signal increase in the middle cerebellar peduncle showed the highest specificity (100%) and had fair sensitivity (85.2%) in MSA-c. Compared between MSA-p and MSA-c, supratentorial parameters were not valid to differentiate MSA-c from MSA-p except for putaminal atrophy. On the contrary, infratentorial parameters were good for distinguishing MSA-c from MSA-p except dilatation of the fourth ventricle. Parkinsonism was not correlated with a hyperintense rim, but cerebellar symptoms were correlated with signal increase in the middle cerebellar peduncle. Our findings suggest the characteristic MRI can be helpful for differentiating MSA-p and MSA-c from PD, respectively, although they do not reflect the presence or lateralization of parkinsonism.

Inflammatory atrophy of the prostate. Prevalence and significance.

Recently, prostatic atrophy associated with chronic inflammation has been linked to carcinoma either directly or indirectly by first developing into high-grade prostatic intraepithelial neoplasia. The purpose of our study was to test this hypothesis in autopsies. A step section method was used to cut the posterior lobe in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsies of men older than 40 years. Prostatic atrophy was classified as simple, hyperplastic (or postatrophic hyperplasia), and sclerotic and was analyzed for the presence of chronic inflammation. Prostatic atrophy without (group A) and with inflammation (group B) was correlated with the following variables: age, race, histologic (incidental) carcinoma, high-grade prostatic intraepithelial neoplasia, and extent of both these lesions. Of the 100 prostates examined, 12%, 22% and 66%, respectively, had no atrophy, atrophy without inflammation (group A), and atrophy with inflammation (group B). There was no statistically significant difference between groups A and B for age (P =.55), race (P =.89), presence of histologic (incidental) carcinoma (P =.89), extensive carcinoma (P =.43), presence of high-grade prostatic intraepithelial neoplasia (P =.65), extensive high-grade intraepithelial neoplasia (P =.30), or subtypes of prostatic atrophy. Neither a topographical relation nor a morphologic transition was seen between prostatic atrophy and histologic carcinoma or high-grade intraepithelial neoplasia. Sclerotic atrophy either alone or combined with other subtypes was more frequent in the group with inflammation. A striking morphologic finding was a topographical relation of focal inflammation with sclerotic atrophy in areas with erosion of the epithelium. Inflammatory prostatic atrophy does not appear to be associated with histologic (incidental) carcinoma or high-grade intraepithelial neoplasia. One possible cause of inflammatory infiltrate associated with prostatic atrophy may be the extravasated prostatic secretions, which were noted in areas of eroded epithelium, a common finding in the sclerotic type of prostatic atrophy.

Inflammatory atrophy of the prostate. Prevalence and significance.

○ Context.-Recently, prostatic atrophy associated with chronic inflammation has been linked to carcinoma either directly or indirectly by first developing into high-grade prostatic intraepithelial neoplasia. Objective.-The purpose of our study was to test this hypothesis in autopsies. Design.-A step section method was used to cut the posterior lobe in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsies of men older than 40 years. Prostatic atrophy was classified as simple, hyperplastic (or postatrophic hyperplasia), and sclerotic and was analyzed for the presence of chronic inflammation. Prostatic atrophy without (group A) and with inflammation (group B) was correlated with the following variables: age, race, histologic (incidental) carcinoma, high-grade prostatic intraepithelial neoplasia, and extent of both these lesions. Results.-Of the 100 prostates examined, 12%, 22% and 66%, respectively, had no atrophy, atrophy without inflammation (group A), and atrophy with inflammation (group B). There was no statistically significant difference between groups A and B for age (P =.55), race (P =.89), presence of histologic (incidental) carcinoma (P =.89), extensive carcinoma (P =.43), presence of high-grade prostatic intraepithelial neoplasia (P =.65), extensive high-grade intraepithelial neoplasia (P =.30), or subtypes of prostatic atrophy. Neither a topographical relation nor a morphologic transition was seen between prostatic atrophy and histologic carcinoma or high-grade intraepithelial neoplasia. Sclerotic atrophy either alone or combined with other subtypes was more frequent in the group with inflammation. A striking morphologic finding was a topographical relation of focal inflammation with sclerotic atrophy in areas with erosion of the epithelium. Conclusions.-Inflammatory prostatic atrophy does not appear to be associated with histologic (incidental) carcinoma or high-grade intraepithelial neoplasia. One possible cause of inflammatory infiltrate associated with prostatic atrophy may be the extravasated prostatic secretions, which were noted in areas of eroded epithelium, a common finding in the sclerotic type of prostatic atrophy.

Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy

Two clinical subtypes of gyrate atrophy (GA) have been defined based on in vivo or in vitro evidence of response to vitamin B6 (pyridoxine), which is the cofactor of the enzyme ornithine aminotransferase (OAT) shown to be defective in GA. We identified the E318K mutation in the OAT gene, heterozygously in three patients and homozygously in one patient, all of whom were vitamin B6-responsive by previous in vivo and in vitro studies. Dose-dependent effects of the E318K mutation were observed in the homo- and heterozygotes in the OAT activity, increase of OAT activity in the presence of pyridoxal phosphate, and apparent Km for pyridoxal phosphate. The highest residual level of OAT activity and mildness of clinical disease correlated directly with the dose of the mutant E318K allele present in the patient.

Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies.

To determine in patients with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (PAPS) the prevalence of cerebral magnetic resonance imaging changes (MRI) and the relationship with antiphospholipid antibodies. Twenty-nine consecutive SLE patients, 24 PAPS patients and 31 healthy controls were prospectively included in the study and underwent MRI Scan over a 1-year period. MRI scans were analyzed separately by a neuroradiologist for white matter changes [periventricular hyperintensity (PVH) (0-6 scale), deep white matter hyperintensity (WMH) (0-24 scale)], and one neurologist for cerebral atrophy (0-39 scale) and stroke subtypes. Statistical assessment consisted of a discriminant analysis performed with SAS-package with MRI data as dependent variables and, as independent variables, age, sex, arterial hypertension, diabetes mellitus, cardiopathy, migraine, neurological symptoms, antiphospholipid antibodies, SLE, steroid treatment. The prevalence of cerebral atrophy was increased in both SLE and PAPS groups relative to controls. PVH and WMH scores were significantly higher in SLE and PAPS than in controls. Focal infarct did not differ in the SLE group when compared with PAPS. PVH and WMH scores were significantly higher in patients with neurological symptoms. Using a correlation test we found a weak significant correlation between cerebral atrophy and lupus anticoagulant. The multivariate analysis found only three independent variables related to PVH and WMH: age, the diagnosis of SLE and cerebral atrophy. Age, presence of SLE and presence of neurological symptoms were independently related with WMH and PVH, but not antiphospholipid antibodies.

Olivopontocerebellar Atrophy with Retinal Degeneration: An Electroretinographic and Histopathologic Investigation

Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures of the brainstem. A deficiency of glutamate dehydrogenase, which results in an excess of glutamate, has been suggested to play a role in the pathogenesis of olivopontocerebellar atrophy. In experimental animals, toxic levels of glutamate are known to cause a selective loss of the b-wave on electroretinographic (ERG) testing and a degeneration of the inner retinal layers. One of the subtypes of olivopontocerebellar atrophy, type II, according to Harding's classification, is associated with retinal degeneration. The authors describe the ophthalmologic and ERG findings in a family with olivopontocerebellar atrophy type II. Histopathologic study of an eye from a 6-year-old family member who died of severe neurologic deterioration secondary to olivopontocerebellar atrophy type II was performed. Electroretinographic changes may be present in affected family members who are entirely asymptomatic and have a normal ophthalmologic evaluation. The changes on the ERG in one patient suggest that cone dysfunction is one of the subtle changes that may be seen in olivopontocerebellar atrophy type II. Our ERG results did not show a selective loss of the b-wave but instead showed a loss of both the a-wave and b-wave in affected family members. Results of light and electron microscopic examination showed diffuse and extensive degeneration of the photoreceptors involving both rods and cones, the most prominent changes being present in the macula. An amorphous debris, presumably degenerated photoreceptors, was noted between the outer nuclear layer and retinal pigment epithelium. Patients with olivopontocerebellar atrophy type II have photoreceptor abnormalities as revealed in abnormal ERGs seen in many patients and histopathologic study of an autopsy eye from an affected 6-year-old boy. Our results do not support the hypothesis that glutamate toxicity may be responsible for the development of retinal degeneration in this condition.