Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.

The value of long-term clinical follow-up for cases of spontaneous carotid cavernous fistula.

To clarify the value of clinical long-term follow-up with radiological examination, ranging from 12 to 63 months (average: 35 months), 18 consecutive patients suffering from spontaneous carotid cavernous fistula (CCF), were studied prospectively. Five aged patients without aggressive symptoms were treated conservatively, and the other 13 underwent transarterial embolization. The radiological follow-up was primarily by magnetic resonance angiography (MRA), performed from 2 to 6 times (average: 4.1 times) during the follow-up period. In three cases, CCFs persisted, but the other fifteen (83%) demonstrated complete cure as defined by long-term follow-up MRA. The three patients with persistent CCFs were comparatively young, less than 60 years old, had no atherosclerotic factors and demonstrated multiple venous drainage routes with cortical venous drainage on angiography. In two of them, the symptoms completely disappeared, and the other had only mild chemosis. However, surprisingly, in two, MRA revealed residual CCF with drainage into only cortical veins through the sphenoparietal sinus, this radiological finding being well known to signify danger. During the follow-up period, central retinal vein thrombosis occurred in two cases. The common point in these cases was that the superior ophthalmic vein was the only venous drainage route. This is also a point requiring care. We therefore emphasize the importance of careful long-term radiological follow-up for spontaneous CCF patients even when their symptoms improve or disappear. MRA is particularly suitable for this purpose and applicable in the out-patient clinic because of its non-invasive nature.

Endovascular approach to a ligated external carotid artery. Technical note.

SUMMARY: A 37-year-old female with left sided multiple congenital haemangiomata presented with repeated haemorrhage. The haemorrhagic origin was from the angiomatous lesion with arteriovenous (AV) shunting in the tongue and pharynx. The patient had already undergone ligation of the external carotid artery. Vascularization was mainly from the portion of the external carotid artery distal to the occlusion. Our first approach via the collateral channels to the haemangioma failed. Through direct puncture of the distal end of the external carotid artery with the use of two dimensional road mapping, we succeeded in catheterizing the distal end of the external carotid artery at the first attempt without placing any pressure on the neck, and carried out selective embolisation without mishap.

Venous ischemia caused by dural arteriovenous malformation. Case report.

A case is presented of tentorial dural arteriovenous malformation (AVM) associated with visual hallucinations and quadrant hemianopsia. Computerized tomography (CT) and magnetic resonance imaging showed an ischemic region, mainly affecting the white matter of the right occipital lobe, that was defined as an area of increased blood volume on dynamic CT scans and as a decrease in cerebral blood flow on N-isopropyl-p-123I-iodoamphetamine single-photon emission CT scans. Angiography demonstrated venous congestion, probably because the retrograde arterial inflow from the dural AVM into the corticomedullary vein was direct and not via the sinuses. The symptoms and radiological findings improved immediately after endovascular treatment. The origin of these symptoms was fully evaluated and confirmed to be a reversible ischemic change caused by disturbance of the volume of venous return over an extensive area.

Narrow energy distribution of output electrons from a modified single channel electron multiplier.

New methods which reduce the unfavorable energy spread of output electrons from a single channel electron multiplier are presented. A modified output electrode produces a pronounced narrowing effect on the energy distribution without much affect on the gain. A simplified analysis of the field inside the channel shows that the fixed channel wall potential near the output end is responsible for the narrow energy distributions obtainable.