Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing

Purpose We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). Methods Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. Results There was no evidence for usefulness of old criteria “glioma“ or “neurofibroma.” “Ependymoma” had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. Conclusions The present study confirms important deficiencies in NF2 diagnostic criteria. The term “glioma” should be dropped and replaced by “ependymoma.” Similarly “neurofibroma” should be removed. Dropping “sibling” from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS

A Case of Superficial Recurrent Ophthalmic Artery Supplying an Infratentorial Vascular Tumour

We present a case of ophthalmic artery contribution to a posterior fossa vascular tumour by the superficial recurrent ophthalmic artery. This branch arises from the second portion of the ophthalmic artery and is rarely seen on angiography. We review the anatomy and embryology of this arterial variant. Furthermore, this case illustrates the capacity of the ophthalmic artery to supply posterior fossa neoplasms. </jats:p

Significance of CSF area measurements in cervical spondylitic myelopathy

Mild clinical myelopathy can occur without cord compression, and asymptomatic cord compression seen on MRI is common. The aim of this study was to ascertain the MRI features which best correlate with early clinical myelopathy. The study was conducted on three groups: group A, 20 patients with clinical myelopathy and MRI evidence of cervical spondylosis; group B, 20 patients without myelopathy, but with other clinical and MRI evidence of cervical spondylosis; and group C, 10 normal volunteers with no MRI evidence of spondylosis. The cross-sectional area (CSA) of the spinal cord (SP-CSA), spinal canal (SC-CSA) and CSF space (CSF-CSA) were measured on T1-weighted axial images at the level of the most severe spinal canal stenosis. The severity of myelopathy was assessed using a simple scoring system giving a score from 0 (normal) to 11 (severe). Subjective demonstration of cord compression on sagittal images was an insensitive indicator of clinical myelopathy. All three measures of cross-sectional area were significantly smaller in Group A than in B (p&lt;0.01). The reduction in SP-CSA was the only independent prognosticator for severity of myelopathy (p&lt;0.005) accounting for 63% of the variation in myelopathy score. All three variables showed a significant correlation with the presence of myelopathy (p&lt;0.01); however, logistic regression analysis showed a decrease in CSF-CSA to be the only independent significant prognosticator of the presence of clinical myelopathy (p&lt;0.02). Reduction of the CSF space to less than 0.7 cm2 was associated with a 90% chance of clinical myelopathy (specificity 83%).</p

The role of MR angiography in the pretreatment assessment of intracranial aneurysms:a comparative study

BACKGROUND AND PURPOSE: With developments in coil technology, intracranial aneurysms are being treated increasingly by the endovascular route. Endovascular treatment of aneurysms requires an accurate depiction of the aneurysm neck and its relation to parent and branch vessels preoperatively. Our goal was to estimate the clinical efficacy of MR angiography (MRA) in the pretreatment assessment of ruptured and unruptured intracranial aneurysms. We compared MRA source data (axial acquired partitions), multiplanar reconstruction (MPR) of these data, as well as maximum intensity projection (MIP) and 3D-isosurface images with intraarterial digital subtraction angiography (IA-DSA).METHODS: The study was performed in 29 patients with 42 intracerebral aneurysms. The MRA data were examined in four different forms--as axial source data, MPR images of the source data, and MIP and 3D isosurface--rendered images. A composite standard of reference for each aneurysm was then constructed using this information together with the IA-DSA findings by looking at aneurysm detection rate, aneurysm morphology, neck interpretation, and branch vessel relationship to the aneurysm. All techniques, including conventional IA-DSA, were then scored independently on a five-point scale from 1 (non diagnostic) to 5 (excellent correlation with the standard of reference) for each of the aneurysm components as compared with the composite picture. An overall score for each technique was also obtained.RESULTS: Of the 42 aneurysms examined, 34 were small (&lt;10 mm), six were large (10-25 mm), and two were giant (&gt;25 mm). Three aneurysms were not detected with MRA. These were smaller than 3 mm and either in an anatomically difficult location (middle cerebral artery bifurcation) or obscured by adjacent hematoma. Two large aneurysms were depicted as undersized by IA-DSA owing to the presence of intramural thrombus shown by MRA axial source data. IA-DSA received the highest scores overall and in three of the four subgroups. Three-dimensional isosurface reconstructions scored higher than did IA-DSA for depiction of the aneurysm neck, although this difference was not significant. The MPR and 3D-isosurface images were comparable to those of IA-DSA in all categories. MPR images were particularly useful for defining branch vessels and the aneurysm neck. MIP images scored poorly in all subgroups (P &lt; .005) compared with IA-DSA findings, except for in aneurysm detection. Source data images were significantly inferior to those of IA-DSA in all categories (P &lt; .005).CONCLUSION: MRA is currently inferior to IA-DSA in pretreatment assessment of intracranial aneurysms, and can miss small lesions (&lt;3 mm). It can, however, provide complementary information to IA-DSA, particularly in anatomically complex areas or in the presence of intramural thrombus. If MRA is used in aneurysm assessment, a meticulous technique with reference to both axial source data and MPR is mandatory. The axial source data should not be interpreted in isolation. Three-dimensional isosurface images are comparable to those of IA-DSA and are more reliable than are MIP images, which should be interpreted with caution.</p