Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in the NF1 gene.

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement. Mosaic activating variants in FGFR1 and KRAS have been reported in several individuals with this syndrome. We report on a patient with neurofibromatosis type 1 (NF1) with a germline pathogenic variant in the NF1 gene and an ECCL phenotype, suggesting ECCL to be part of a spectrum of malformations associated with NF1 pathogenic variants. An anatomical hemispherectomy was performed for intractable epilepsy. Through genetic analysis of blood, cerebral tissue and giant cell lesions in both jaws, we identified the germline NF1 pathogenic variant in all samples and a second-hit pathogenic NF1 variant in cerebral tissue and both giant cell lesions. Both NF1 variants were located on different alleles resulting in somatic mosaicism for a biallelic NF1 inactivation originating in early embryogenesis (second-hit mosaicism or Happle type 2 mosaicism). The biallelic deficit in NF1 in the left hemicranium explains the severe localised, congenital abnormality in this patient. Identical first and second-hit variants in a giant cell lesion of both upper and lower jaws provide confirmatory evidence for an early embryonic second hit involving at least the neural crest. We suggest that the ECCL phenotype may be part of a spectrum of congenital problems associated with mosaic NF1 nullisomy originating during early embryogenesis. The biallelic NF1 inactivation during early embryogenesis mimics the severe activation of the RAS-MAPK pathway seen in ECCL caused by embryonic mosaic activating FGFR1 and KRAS variants in the cranial region. We propose that distinct mechanisms of mosaicism can cause the ECCL phenotype through convergence on the RAS-MAPK pathway.

Delayed Intraventricular Pneumocephalus Following Shunting for Normal-Pressure Hydrocephalus.

BACKGROUND: Pneumocephalus is usually seen in trauma or cranial surgery. It is rarely reported as a delayed complication of ventriculoperitoneal shunt placement for hydrocephalus secondary to trauma, tumor, or aqueduct stenosis. We describe a case of intraventricular pneumocephalus manifesting 10 months after placement of a shunt for normal-pressure hydrocephalus. CASE DESCRIPTION: A pressure-regulated ventriculoperitoneal shunt was implanted in an 81-year-old patient after diagnosis of normal-pressure hydrocephalus. He showed postoperative clinical improvement. Routine computed tomography performed 2 months after the procedure showed no abnormalities. He presented 10 months after shunting with a subacute deterioration of gait. Imaging revealed major intraventricular pneumocephalus and a left-sided temporal porencephalic cyst with a small, bony defect in the left petrous bone. A middle fossa approach was performed, and the temporal defect was covered with fascia of the temporal muscle. This resulted in a gradual resolution of pneumocephalus. CONCLUSIONS: Pneumocephalus after shunting for NPH is rare and described as a complication only during the first 2 postoperative months. This case is unique, as the pneumocephalus developed 10 months after shunting. The combination of an occult, possibly congenital, skull base defect and the insertion of a shunt resulted in delayed intraventricular and intraparenchymal pneumocephalus.

Posterior Quadrant Disconnection: A Fiber Dissection Study.

BACKGROUND: Posterior quadrant disconnection can be highly effective in the surgical treatment of selected cases of refractory epilepsy. The technique aims to deafferent extensive areas of epileptogenic posterior cortex from the rest of the brain by isolating the temporoparietooccipital cortex. OBJECTIVE: To describe this procedure and relevant white matter tracts with a specific emphasis on the extent of callosotomy in an anatomic study. METHODS: Twenty hemispheres were dissected according to Klingler's fiber dissection technique illustrating the peri-insular (temporal stem, superior longitudinal fasciculus, corona radiata) and mesial disconnection (mesiotemporal cortex, cingulum, and corpus callosum). RESULTS: Extensive white matter tract disconnection is obtained after posterior quadrant disconnection. Callosal fibers connecting the anterior most part of the parietal cortex invariably ran through the isthmus of the corpus callosum and need to be disconnected, while frontal lobe connections including the corticospinal tract and the anterior two-thirds of the corpus callosum are spared during the procedure. CONCLUSION: Our findings suggest the involvement of both the splenium and the isthmus in interhemispheric propagation in posterior cortex epilepsies. Sectioning the total extent of the posterior one-third of the corpus callosum might therefore be necessary to achieve optimal outcomes in posterior quadrant epilepsy surgery.

Pseudotumoral rebound of multiple sclerosis in a pregnant patient after stopping natalizumab.

Natalizumab is a highly efficacious treatment for active relapsing-remitting multiple sclerosis, dramatically reducing both clinical and radiological signs of inflammation in most patients. The disease course after stopping treatment and especially the emergence of rebound activity are still a matter of debate. We present a case of dramatic reactivation of clinical disease activity with newly emerging pseudotumoral lesions in a patient who stopped treatment due to pregnancy. Both the clinical and radiological presentation suggest a rebound and necessitate close monitoring of patients stopping their treatment during pregnancy, even after a long period of stable disease.