Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, and Nasu Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy are both underrecognized progressive degenerative white matter diseases that can present with young dementia, leukoencephalopathy and brain calcifications. We report and compare three cases in terms of clinical phenotype, imaging and neuropathological findings. Both cases have led to the identification of two novel causal mutations.

Diagnosis and treatment of a superficial upper eyelid arteriovenous malformation.

UNLABELLED: Combined embolization and surgical excision as a safe treatment for a high flow superficial upper eyelid anteriovenous malformation. INTRODUCTION: Orbital arteriovenous malformations (AVM) may cause significant morbidity including chronic pain and cosmetic disfigurement. These rare lesions require a multidisciplinary approach. A case of an orbital high-flow AVM treated subsequently by an mterventional radiologist and oculoplastic surgeon is presented. MATERIALS AND METHODS: Clinical assessment, computed tomography and digital substruction angiography revealed a high-flow AVM. Transvenous and percutaneous embolization was followed by surgical excision. RESULTS: A 1.5 cm, slowly growing, compressible pulsating lesion in the left upper eyelid of a 23 year old man was found. Eye motility and ophthalmologic examination were normal. Valsava manoeuvre didn't increase the size. Imaging revealed a high-flow AVM feeded by the arteria temporalis superficialis (itself feeded by the a. supraorbitalis and supratrochlearis). Draining vessels were the superior ophthalmic vein and a superficial lateral orbital vein. This malformation was first embolized. To prevent iatrogenic embolization of the sinus cavernous, the vein draining into the superior ophthalmic was occluded by a transvenous approach, followed by a percutaneous injection with diluted glue (equal amounts of glubran-2 and lipiodol). The remaining low-flow lesion was then safely excised. CONCLUSION: High-flow orbital AVM represent a considerable treatment challenge. Good cosmetical and functional outcome was obtained safely by subsequent embolization and surgical excision. When treating these rare malformations it is of the highest importance to coordinate the interdisciplinary efforts.

Prune belly anomaly on prenatal ultrasound as a presenting feature of ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC).

We report on a fetus with prune belly anomaly presenting at 16 weeks gestation. Clinical evaluation after birth revealed other malformations reminiscent of the EEC syndrome. This diagnosis was also suspected in the mother and finally confirmed in both relatives by identification of a heterozygous mutation (p.R204W) in the p63 gene. With this paper we confirm the previously reported occurrence of prune belly anomaly in the EEC syndrome, however here in this family proven by genetic analysis.

The hTERT protein as a marker for malignancy in meningiomas.

The meningioma evolution remains problematic as 6 to 19% relapse after total resection. We have no criterion or marker to predict with certainty the tumour behaviour, and the WHO grading system is to a certain degree controversial. Telomerase expression seems to play an active role in conferring to the tumour cell indefinite life span. Telomerase activity has been documented via TRAP protocol and telomerase messenger expression (hTERT mRNA). In meningiomas the protein hTERT itself has not been studied directly. Thirty tumour samples of meningiomas operated in our Neurosurgical Department are reviewed with a mean follow-up of 4 years. Specifically hTERT protein, resection type, proliferation markers (Ki-67), and recurrences are evaluated. MRI is used for recurrence controls. Seven samples appeared to be hTERT-positive and all seven showed recurrence. Four patients had undergone a subtotal resection (STR). Among them two were hTERT-positive; only these showed recurrence and malignancy. Of the five macroscopically total resections (MTR), two were initially histologically benign and progressed to malignancy. A strong correlation was found between hTERT and recurrences (coefficient=0.989; p=0,01) with the Spearman's rho test, and weaker one between the Ki-67 and hTER (coefficient=0.672; p<0.0001). The hTERT staining revealed the presence of the hTERT protein not only in their nucleoli but sometime outside as nuclear speckles. The presence of nucleolar or subnuclear hTERT is directly correlated to recurrence and progression towards malignancy. Relocalisation of this protein was confirmed. A distinction is proposed between regrowth, based on normal proliferation (Ki-67) which can accompany subtotal resection and recurrence. Recurrence appears to be pathologic proliferation linked to hTERT presence. The hTERT presence predicts a sombre clinical outcome at mid-term for the individual patient.

Differential in situ expression of cytokines in renal allograft rejection.

The expression of the interleukin 6, tumor necrosis factor alpha, and interferon gamma (IFN-gamma) genes was studied in human renal biopsies from individuals without evidence of kidney disease and from patients undergoing acute renal allograft rejection using a method of in situ hybridization capable of detecting 1-5 copies of a specific cellular messenger RNA in individual cells. IL-6, TNF-alpha, and IFN-gamma RNA transcripts were not detected in any of the sections of normal human kidneys. Elevated levels of IL-6 mRNA but not IFN-gamma were, however, detected in the sections of the renal biopsies from six of eight patients exhibiting acute rejection. A uniform level of expression of IL-6 mRNA was observed in all the cells examined, including glomerular cells, tubular epithelia, smooth muscle cells, and vascular endothelia, as well as the interstitial mononuclear infiltrate. Juxtatabular clusters of TNF-alpha mRNA were detected in the absence of IL-6 mRNA in one patient exhibiting acute rejection. Only a small number of grains (1-5 per high-power field) was detected in the urinary space or in the tubular or vascular lumen following hybridization with the IL-6 or TNF-alpha probes. In contrast, in kidney transplant patients with stable renal function no significant labeling was observed with the IL-6, TNF-alpha, or IFN-gamma probes. A similar level of expression of actin mRNA was observed in all the sections of normal and transplanted kidneys studied, suggesting that the overall level of RNA synthesis was similar in both groups. These results suggest that cytokines such as IL-6 play a role in acute allograft rejection.