Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 54-year-old woman was hospitalized because of paraparesis, sensory disturbance of the lower extremities, and dysuria. Laboratory data included an erythrocyte sedimentation rate (ESR) of 16 mm/h and lactate dehydrogenase (LDH) level of 459 IU/l. Myelogram showed an enlarged spinal cord at the L1 level, and spinal MRI revealed a high signal area on T2-weighted images. Spinal cord biopsy by thoraco-lumbar laminectomy showed thickening of the pia mater and neovascularization, but no malignant cells. Immediately after the operation, the patient displayed progressive mental deterioration. Cranial MRI showed widespread high signal areas in the cerebral white matter on T2-weighted images which resembled those of leukoencephalopathy. Steroid therapy was tried but was ineffective. Ten months after the onset of symptoms, a brief period of regression of both clinical symptoms and MRI appearances occurred following the administration of Inosiplex, subsequent progressive deterioration led to death 14 months after the onset of symptoms. LDH, C-reactive protein (CRP), and cerebrospinal fluid (CSF) protein were all elevated during the deterioration of her general status. Postmortem examination revealed a large tumor mass of the left adrenal gland which extended to the Th12, L1, and L2 vertebrae and remarkable brain edema. Microscopic mononuclear tumor cells were widespread but confined to the lumens of small vessels of the brain, spinal cord, spinal root and right adrenal gland, almost as if they were occluded. Cerebral white matter presented widespread multiple small infarcts and extensive myelin thinning. In addition to the left adrenal gland, interstitial invasions of tumor cells were discovered in the kidneys, iliopsoas muscles, oviducts, myocardium, lymph nodes, and thyroid gland.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsied case of intravascular malignant lymphomatosis with paraparesis, that presented a leukoencephalopathy-like image after spinal cord biopsy]. 836 55

To investigate changes in caliber of vessels in leukoencephalopathy with cerebral amyloid angiopathy (CAA) we performed a histological and morphometric study of cerebral arteries in this disease. We histologically examined changes in cortico-leptomeningeal arteries in five cases of leukoencephalopathy with CAA and compared their morphometrically determined wall-to-lumen ratio [(external diameter-internal diameter) x 0.5/internal diameter] with those of amyloid-negative arteries to estimate stenotic changes. Additionally, we compared wall-to-lumen ratios of medullary arteries in brains with CAA and white matter lesions (WML) (CAA(+)/WML(+), n = 5), subcortical arteriosclerotic encephalopathy without CAA (CAA(-)/WML(+), n = 7), and neither CAA nor white matter lesions (CAA(-)/WML(-), n = 5). Amyloid-positive arteries had thinned walls and dilated lumens. The external diameter and the wall-to-lumen ratio for amyloid-positive arteries was smaller than for amyloid-negative arteries in CAA(+)/WML(+) brains. There was no significant difference in the external diameters among the three groups. The wall-to-lumen ratio for medullary arteries in CAA(-)/WML(+) brains was significantly greater than for CAA(+)/WML(+) and CAA(-)/WML(-), but there was no significant difference between CAA(+)/WML(+) and CAA(-)/WML(-). Amyloid deposition causes degeneration of the tunica media, resulting in thinning of the wall and dilation of the lumen. The tunica media of small arteries is important in regulation of cerebral blood flow with degeneration causing impairment of cerebrovascular autoregulation in response to blood pressure. This impairment may lead to white matter lesions.
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PMID:Leukoencephalopathy with cerebral amyloid angiopathy: a semiquantitative and morphometric study. 1046 Apr 41

A 5 yr old girl is reported with patchy white matter lesions, cystic degeneration of the temporal tips, normal cortex, and normal cerebellum, documented by FLAIR, and diffusion-weighted MRI. This condition differed from the entity megalencephalic leukoencephalopathy with cysts by lack of diffuse involvement of the white matter and cortical thinning, by presence of a normal head size, and existence of a non-progressive, severe clinical condition. Occurrence of cystic degeneration in the temporal tips distinguished the condition from other leukoencephalopathies. This leukoencephalopathy appears to be a new distinct entity.
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PMID:Leukoencephalopathy with patchy lesions, temporal cystic degeneration, and normal head size. 1257 93

To describe the morphologic magnetic resonance imaging (MRI) findings in histologically proven therapy-induced cerebral necrosis. We retrospectively reviewed the morphologic MRI findings in patients with therapy-induced cerebral necrosis. Images were reviewed for size, location, and characteristics of signal intensity abnormalities and T1-contrast enhancement. Images were also assessed for mass effect, necrosis, cyst, atrophy, cortical thinning, and leukoencephalopathy. The individual imaging characteristics were correlated with clinical and treatment variables. There were 44 patients. Seventy percent had a glioma, all patients had received radiation, and 57% had received chemotherapy in close proximity to radiation. All images demonstrated contrast enhancement, predominantly in the white matter. Enhancement was present in the periventricular/subependymal region in 50% of cases and the corpus callosum in 27%. The most common pattern of lesion peripheral enhancement was "spreading wavefront" and of interior enhancement was "Swiss cheese/soap bubble." The enhancing lesion was single in 60% of cases. Mass effect was present in 93% of patients. Location and patterns of enhancement were significantly associated with the interval from brain radiation to the diagnosis of therapy-induced cerebral necrosis, tumor histology, patient age, type of radiation, and administration of systemic chemotherapy. This is the largest study of the morphologic conventional MRI findings in pathologically confirmed therapy-induced cerebral necrosis. We characterized the imaging findings in a variety of tumor types following a variety of radiation treatments and other antineoplastic therapy. These findings may be of value in identifying therapy-induced cerebral necrosis in patients treated for a brain tumor.
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PMID:Morphologic magnetic resonance imaging features of therapy-induced cerebral necrosis. 2049 Jun 12

Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r+/- and control Csf1r+/+ mice. Six to 8-month old Csf1r+/- mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior. MRIs of one year-old Csf1r+/- mice reveal lateral ventricle enlargement and thinning of the corpus callosum. Ultrastructural analysis of the corpus callosum uncovers dysmyelinated axons as well as neurodegeneration, evidenced by the presence of axonal spheroids. Histopathological examination of 11-week-old mice reveals increased axonal and myelin staining in the cortex, increase of neuronal cell density in layer V and increase of microglial cell densities throughout the brain, suggesting that early developmental changes contribute to disease. By 10-months of age, the neuronal cell density normalizes, oligodendrocyte precursor cells increase in layers II-III and V and microglial densities remain elevated without an increase in astrocytes. Also, the age-dependent increase in CSF-1R+ neurons in cortical layer V is reduced. Moreover, the expression of Csf2, Csf3, Il27 and Il6 family cytokines is increased, consistent with microglia-mediated inflammation. These results demonstrate that the inactivation of one Csf1r allele is sufficient to cause an ALSP-like disease in mice. The Csf1r+/- mouse is a model of ALSP that will allow the critical events for disease development to be determined and permit rapid evaluation of therapeutic approaches. Furthermore, our results suggest that aberrant activation of microglia in Csf1r+/- mice may play a central role in ALSP pathology.
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PMID:Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP). 2549 33

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s-50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.
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PMID:CSF1R-related leukoencephalopathy: A major player in primary microgliopathies. 3042 77

A 64-year-old woman visited our hospital with early-onset dementia and progressive gait disturbance. She had demonstrated a mild communication disorder at the age of ~40 years; however, her psychiatric symptoms at that time were mild and were not accompanied by social problems. At the age of 59, she presented with memory loss, visual hallucinations, and delusions. Over the following five years she developed gait difficulties that gradually deteriorated and suffered frequent falls. On admission, neurological examinations revealed severe pyramidal and extrapyramidal signs of akinetic mutism. MRI of the brain showed cerebral atrophy, enlarged lateral ventricles, thinning of the corpus callosum, and leukoencephalopathy in the frontal-parietal lobes. Additionally, CT revealed a small spotty calcification in the frontal subcortical white matter. Genetic analysis revealed a single-base substitution (c.2330G>A/p.R777Q) in exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene, encoding the CSF1R protein. She was diagnosed with hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS is included in the differential diagnosis of early-onset dementia and should be considered in patients with mild personality change and abnormal behavior in the early course of the illness.
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PMID:[A case of hereditary diffuse leukoencephalopathy with spheroids and pigmented glia presenting with long-term mild psychiatric symptoms]. 3243 43

Adult-onset diffuse leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare progressive degenerative white matter disease caused by mutations in the colony-stimulating factor-1 receptor gene. Patients commonly present in the 4th or 5th decade with variable clinical presentations including behavioral changes, dementia, parkinsonism, and motor dysfunctions, eventually leading to death within a few years. Although the disease is typically hereditary, sporadic cases are known to occur. The classic MRI features of ALSP include T2 hyperintensities in the frontal and parietal white matter, scattered foci of restricted diffusion in the white matter, age-advanced cerebral involutional changes, thinning and signal changes in the corpus callosum, absence of infratentorial involvement and lack of enhancement. CT commonly shows tiny calcifications in the corpus callosum and deep white matter. We report a unique case of sporadic ALSP that initially presented as young stroke with acute onset of left-sided hemiparesis and no preceding history of cognitive decline. However, subsequent cognitive and behavioral changes lead to the consideration of an alternative diagnosis. Stroke-like symptoms is a very rare primary presentation of this disease entity. We have highlighted the classic MRI and CT features that helped to guide its diagnosis in our patient and prompted early corroborative genetic testing.
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PMID:Adult-onset diffuse leukoencephalopathy with axonal spheroids and pigmented glia presenting with acute stroke-like symptoms: A rare clinical scenario. 3287 84