Epilepsy, Complex Partial

Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.

Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n = 17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches.

Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM.

Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease.

Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council.

This report presents a case of medically refractory dystonia in a pediatric patient successfully treated with bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) while under general anesthesia by using microelectrode recordings (MERs) with intraoperative computed tomography (CT).

The patient was an 18-year-old female with primary dystonia secondary to mitochondrial Leigh syndrome. Her past medical history was significant for complex partial epilepsy and hearing loss treated with cochlear implants. Her cochlear implants precluded anatomical targeting via magnetic resonance imaging. Additionally, the patient could not tolerate awake surgery with MER. The decision was made to proceed with bilateral STN DBS with intraoperative CT with the patient under general anesthesia. The patient's cochlear implants made standard frame placement difficult, so navigation was performed with the Nexframe system. Recordings were obtained with the patient under general anesthesia with ketamine, dexmedetomidine, and remifentanil. At the 3- and 6-month follow-ups, the patient demonstrated marked improvement in dystonia without neurological complications.

This is the first case of dystonia secondary to Leigh syndrome treated with DBS. Additionally, the authors describe the novel use of the Nexframe for DBS lead placement in a pediatric patient. This demonstrates that STN DBS with the use of MER and intraoperative CT can be a safe and effective method of treating dystonia in certain pediatric patients.

In patients with pelvic venous disorders (PeVD) secondary to pelvic venous insufficiency (PVI), the optimal imaging modality is ill-defined. Trans-abdominal ultrasongraphy (TAU) is widely utilized to identify the presence of an iliac vein stenosis. The purpose of this investigation is to determine the accuracy of TAU for determining the presence of an iliac vein area reducing lesion compared to intra-vascular ultrasound (IVUS).

From January to December 2020, a retrospective review of prospectively collected data in 96 patients treated for symptomatic PVI at the Center for Vascular Medicine was performed. All patients had complete history and physicals, demographics, CEAP, rVCSS, TAU, diagnostic venography and IVUS measurements recorded in our electronic medical record system. All TAU measurements were performed by the same ultrasound technician in the supine position and iliac vein diameters of the common femoral, external iliac, common iliac veins and the inferior vena cava were obtained. Differences in body habitus were normalized by dividing the minimum diameter measurement of the stenotic vessel to the ipsilateral common femoral vein, subtracting this number from 1 and multiplying by 100 (Stenosis=(1-Minimal diameter/common femoral diameter)x 100). The normalized stenoses were then compared to IVUS derived area reducing measurements. A receiver operator curve was created and a logistic regression analysis for the probability of predicting an area reducing lesion of greater than 50% and 60% with TAU was performed. Sensitivity, specificity, positive and negative predictive values were subsequently calculated.

The average age of the entire cohort was 49.8 ± 13.5 years with 69 females and 27 males. The CEAP distribution was the following: C0 (5%), C1 (5%), C2 (10%), C3 (40%), C4a,b (30%), C5 (7%), C6 (3%). The average rVCSS was 6.2 ± 2.6. Indications for intervention were leg symptoms alone in 43%, pelvic symptoms alone in 3%, and combined leg and pelvic symptoms in 54%. TAU identified a stenosis of 50% or greater in 92/96 (96%) of patients. For a 50% or greater stenosis, a normalized diameter of 3 millimeters or less demonstrated a sensitivity, specificity, positive and negative predictive value of 75%, 75%, 98% and 12%. The logistic regression analysis indicated that TAU was significant in predicting the presence of a 60% or greater area reducing lesion (OR=1.03, 95% CI: 1.01, 1.05, and p-value=0.009). The area under the receiver operator curve (c-statistic) was 68.6%. The sensitivity, specificity, positive and negative predictive values were 66.7%, 66.7%, 81.5%, and 47.6% for a normalized diameter of 4 millimeters or less.

The ability of TAU to identify an iliac vein stenosis of 50% or greater is 96%. The positive predictive value of TAU for identifying a 60% or greater iliac vein area reducing lesion is high with moderate sensitivity and specificity. For patients with symptoms consistent with a PeVD secondary to PVI, TAU is a good pre-intervention screening modality in properly trained vascular imaging specialists that correlates well with IVUS measurements.