Treatment of a symptomatic cervical cerebrospinal fluid fistula after full endoscopic cervical foraminotomy with CT-guided epidural fibrin patch

Background There is only limited data on the management of cerebrospinal fluid (CSF) fistulas after cervical endoscopic spine surgery. We investigated the current literature for treatment options and present a case of a patient who was treated with CT-guided epidural fibrin patch. Methods We present the case of a 47-year-old female patient with a suspected CSF fistula after endoscopic decompression for C7 foraminal stenosis. She was readmitted 8 days after surgery with dysesthesia in both upper extremities, orthostatic headache and neck pain, which worsened during mobilization. A CSF leak was suspected on spinal magnetic resonance imaging. A computer tomography (CT)-guided epidural blood patch was performed with short-term relief. A second CT-guided epidural fibrin patch was executed and the patient improved thereafter and was discharged at home without sensorimotor deficits or sequelae. We investigated the current literature for complications after endoscopic spine surgery and for treatment of postoperative CSF fistulas. Results Although endoscopic and open revision surgery with dura repair were described in previous studies, dural tears in endoscopic surgery are frequently treated conservatively. In our case, the patient was severely impaired by a persistent CSF fistula. We opted for a less invasive treatment and performed a CT-guided fibrin patch which resulted in a complete resolution of patient’s symptoms. Discussion and conclusion CSF fistulas after cervical endoscopic spine procedures are rare complications. Conservative treatment or revision surgery are the standard of care. CT-guided epidural fibrin patch was an efficient and less invasive option in our case

Hydrocephalus, cerebral vasospasm, and delayed cerebral ischemia following non-aneurysmatic spontaneous subarachnoid hemorrhages: an underestimated problem

Non-aneurysmal subarachnoid hemorrhage (NASAH) is rare and mostly benign. However, complications such as cerebral vasospasm (CV), delayed cerebral ischemia (DCI), or post-hemorrhagic hydrocephalus (HC) may worsen the prognosis. The aim of this study was to evaluate the rate of these complications comparing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH. Monocentric, retrospective analysis of patients diagnosed with NASAH from 01/2010 to 01/2021. Diagnosis was set only if vascular pathologies were excluded in at least one digital subtraction angiography, and NASAH was confirmed by cranial computed tomography (cCT) or lumbar puncture (LP). One hundred patients (62 female) with a mean age of 54.9 years (27–84) were identified. Seventy-three percent had a World Federation of Neurological Surgeons (WFNS) grading scale score I, while 9% were WFNS score IV or V at the time of admission. SAH was diagnosed by cCT in 86%, in 14% by lumbar puncture. Twenty-five percent necessitated short-term CSF diversion by extraventricular drainage or lumbar drainage, whereof 7 suffered from long-term HC treated with ventriculoperitoneal shunting (VPS). One patient without a short-term CSF drainage developed long-term HC. Ten percent developed CV, four of whom received intraarterial spasmolysis. Radiological DCI was diagnosed in 2%; none of these correlated with CV. Despite a mortality of 3% occurring solely in NPM SAH, the analyzed complication rate was comparable in both groups. We observed post-hemorrhagic complications in 35% of cases during the first 3 weeks after bleeding, predominantly in patients with NPM SAH. For this reason, close observation and cranial imaging within this time may be indicated not to overlook these complications

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

BACKGROUND DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. OBJECTIVE To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. METHODS We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. RESULTS First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. CONCLUSIONS STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features

Development of a highly effective combination monoclonal antibody therapy against Herpes simplex virus.

BACKGROUND Infections with Herpes simplex virus (HSV)-1 or -2 usually present as mild chronic recurrent disease, however in rare cases can result in life-threatening conditions with a large spectrum of pathology. Monoclonal antibody therapy has great potential especially to treat infections with virus resistant to standard therapies. HDIT101, a humanized IgG targeting HSV-1/2 gB was previously investigated in phase 2 clinical trials. The aim of this study was to develop a next-generation therapy by combining different antiviral monoclonal antibodies. METHODS A lymph-node derived phage display library (LYNDAL) was screened against recombinant gB from Herpes simplex virus (HSV) -1 and HDIT102 scFv was selected for its binding characteristics using bio-layer interferometry. HDIT102 was further developed as fully human IgG and tested alone or in combination with HDIT101, a clinically tested humanized anti-HSV IgG, in vitro and in vivo. T-cell stimulating activities by antigen-presenting cells treated with IgG-HSV immune complexes were analyzed using primary human cells. To determine the epitopes, the cryo-EM structures of HDIT101 or HDIT102 Fab bound to HSV-1F as well as HSV-2G gB protein were solved at resolutions < 3.5 Å. RESULTS HDIT102 Fab showed strong binding to HSV-1F gB with Kd of 8.95 × 10-11 M and to HSV-2G gB with Kd of 3.29 × 10-11 M. Neutralization of cell-free virus and inhibition of cell-to-cell spread were comparable between HDIT101 and HDIT102. Both antibodies induced internalization of gB from the cell surface into acidic endosomes by binding distinct epitopes in domain I of gB and compete for binding. CryoEM analyses revealed the ability to form heterogenic immune complexes consisting of two HDIT102 and one HDIT101 Fab bound to one gB trimeric molecule. Both antibodies mediated antibody-dependent phagocytosis by antigen presenting cells which stimulated autologous T-cell activation. In vivo, the combination of HDIT101 and HDIT102 demonstrated synergistic effects on survival and clinical outcome in immunocompetent BALB/cOlaHsd mice. CONCLUSION This biochemical and immunological study showcases the potential of an effective combination therapy with two monoclonal anti-gB IgGs for the treatment of HSV-1/2 induced disease conditions