Gregor Antoniadis

High-resolution ultrasonography in evaluating peripheral nerve entrapment and trauma

High-resolution ultrasonography is a noninvasive, readily applicable imaging modality, capable of depicting real-time static and dynamic morphological information concerning the peripheral nerves and their surrounding tissues. Continuous progress in ultrasonographic technology results in highly improved spatial and contrast resolution. Therefore, nerve imaging is possible to a fascicular level, and most peripheral nerves can now be depicted along their entire anatomical course. An increasing number of publications have evaluated the role of high-resolution ultrasonography in peripheral nerve diseases, especially in peripheral nerve entrapment. Ultrasonography has been shown to be a precious complementary tool for assessing peripheral nerve lesions with respect to their exact location, course, continuity, and extent in traumatic nerve lesions, and for assessing nerve entrapment and tumors. In this article, the authors discuss the basic technical considerations for using ultrasonography in peripheral nerve assessment, and some of the clinical applications are illustrated.

fMRI for preoperative neurosurgical mapping of motor cortex and language in a clinical setting.

Purpose Identification of the precentral gyrus can be difficult in patients with brain tumors. The purpose of the current study was to evaluate the clinical usefulness of functional MRI (fMRI) in identifying motor cortex and speech areas as a part of preoperative neurosurgical planning. Method fMRI was performed using a 1.5 T MR unit in 41 patients with brain tumors. The motor paradigm was finger tapping and foot movement, whereas the language paradigm consisted of a two word semantic test. Statistical analysis of the data was done using the Kolmogorow-Smirnow test. Plots of signal intensities over time were created. Results The precentral gyrus was identified in 38 of 41 patients. In two patients, fMRI was not of acceptable quality due to motion artifacts. Speech areas were localized in 33 patients. In a typical clinical setting, the value of the method was graded “high.” Conclusion fMRI`s efficacy in the preoperative localization of language and motor areas is high. The method should become a routine adjunct for preoperative evaluation of brain tumors in the near future.

Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells

Neurogenesis in the adult human brain occurs within two principle neurogenic regions, the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Recent reports demonstrated the isolation of human neuroprogenitor cells (NPCs) from these regions, but due to limited tissue availability the knowledge of their phenotype and differentiation behavior is restricted. Here we characterize the phenotype and differentiation capacity of human adult hippocampal NPCs (hNPCs), derived from patients who underwent epilepsy surgery, on various feeder cells including fetal mixed cortical cultures, mouse embryonic fibroblasts (MEFs) and PA6 stromal cells. Isolated hNPCs were cultured in clonal density by transferring the cells to serum‐free media supplemented with FGF‐2 and EGF in 3% atmospheric oxygen. These hNPCs showed neurosphere formation, expressed high levels of early neuroectodermal markers, such as the proneural genes NeuroD1 and Olig2, the NSC markers Nestin and Musashi1, the proliferation marker Ki67 and significant activity of telomerase. The phenotype was CD15low/–, CD34–, CD45– and CD133–. After removal of mitogens and plating them on poly d‐lysine, they spontaneously differentiated into a neuronal (MAP2ab+), astroglial (GFAP+), and oligodendroglial (GalC+) phenotype. Differentiated hNPCs showed functional properties of neurons, such as sodium channels, action potentials and production of the neurotransmitters glutamate and GABA. Co‐culture of hNPCs with fetal cortical cultures, MEFs and PA6 cells increased neurogenesis of hNPCs in vitro, while only MEFs and PA6 cells also led to a morphological and functional neurogenic maturation. Together we provide a first detailed characterization of the phenotype and differentiation potential of human adult hNPCs in vitro. Our findings reinforce the emerging view that the differentiation capacity of adult hNPCs is critically influenced by non‐neuronal mesodermal feeder cells.

Transcription profiling of adult and fetal human neuroprogenitors identifies divergent paths to maintain the neuroprogenitor cell state.

Global gene expression profiling was performed using RNA from adult human hippocampus‐derived neuroprogenitor cells (NPCs) and multipotent frontal cortical fetal NPCs compared with adult human mesenchymal stem cells (hMSCs) as a multipotent adult stem cell control, and adult human hippocampal tissue, to define a gene expression pattern that is specific for human NPCs. The results were compared with data from various databases. Hierarchical cluster analysis of all neuroectodermal cell/tissue types revealed a strong relationship of adult hippocampal NPCs with various white matter tissues, whereas fetal NPCs strongly correlate with fetal brain tissue. However, adult and fetal NPCs share the expression of a variety of genes known to be related to signal transduction, cell metabolism and neuroectodermal tissue. In contrast, adult NPCs and hMSCs overlap in the expression of genes mainly involved in extracellular matrix biology. We present for the first time a detailed transcriptome analysis of human adult NPCs suggesting a relationship between hippocampal NPCs and white matter‐derived precursor cells. We further provide a framework for standardized comparative gene expression analysis of human brain‐derived NPCs with other stem cell populations or differentiated tissues.

The influence of prophylactic vasoactive treatment on cochlear and facial nerve functions after vestibular schwannoma surgery: a prospective and open-label randomized pilot study.

OBJECTIVE Facial nerve paresis and hearing loss are common complications after vestibular schwannoma surgery. Experiments with facial nerves of the rat and retrospectively analyzed clinical studies showed a beneficial effect of vasoactive treatment on the preservation of facial and cochlear nerve functions. This prospective and open-label randomized pilot study is the first study of a prophylactic vasoactive treatment in vestibular schwannoma surgery. METHODS Thirty patients were randomized before surgery. One group (n = 14) received a vasoactive prophylaxis consisting of nimodipine and hydroxyethylstarch which was started the day before surgery and was continued until the seventh postoperative day. The other group (n = 16) did not receive preoperative medication. Intraoperative monitoring, including acoustic evoked potentials and continuous facial electromyelograms, was applied to all patients. However, when electrophysiological signs of a deterioration of facial or cochlear nerve function were detected in the group of patients without medication, vasoactive treatment was started immediately. Cochlear and facial nerve function were documented preoperatively, during the first 7 days postoperatively, and again after long-term observation. RESULTS Despite the limited number of patients, our results were significant using the Fishers exact test (small no. of patients) for a better outcome after vestibular schwannoma surgery for both hearing (P = 0.041) and facial nerve (P = 0.045) preservation in the group of patients who received a prophylactic vasoactive treatment. CONCLUSION Prophylactic vasoactive treatment consisting of nimodipine and hydroxyethylstarch shows significantly better results concerning preservation of the facial and cochlear nerve function in vestibular schwannoma surgery. The prophylactic use is also superior to intraoperative vasoactive treatment.

Results of DREZ coagulations for pain related to plexus lesions, spinal cord injuries and postherpetic neuralgia

SummaryThe results of 58 dorsal root entry zone (DREZ) thermocoagulation procedures in 51 patients are reported. The postoperative analgesic effect was judged by the patients as being good (more than 75% pain reduction), fair (25–75% pain reduction) or poor (less than 25% pain reduction). Of the 14 patients who underwent surgery for pain due to cervical root avulsion, 10 (77%) had permanently good (8) or fair (2) pain relief after a mean follow up period of 76 months, another 2 (15%) experienced recurrence to the pre-operative level (initially 1 good, 1 fair) after more than 2 and 4 years, respectively. Twenty two paraplegics were operated upon, 3 of whom twice, for intractable pain. After a mean observation time of 54 months, continuing pain relief was reported by 12 (55%) patients (11 good, 1 fair), and one (initially fair) had recurrent pain after 8 months. All 3 (early) re-operations remain successful for an average period of 75 months. Poor results were seen especially in cases of associated spinal cord cysts (5 out of 7), despite combined drainage, and in patients with diffuse pain distribution (5 out of 6). Continuous marked improvement for longer periods (mean follow up: 52 months) after DREZ lesions was reported only by 2 out of 10 patients with postherpetic neuralgia (12 procedures) and by 1 out of 5 with painful states due to radiation-induced brachial plexopathy (2), previous surgery (2) and malignant tumour infiltration of the brachial plexus (1). Three patients died postoperatively due to acute cardiac failure (2) and pulmonary embolism (1). Major complications, especially permanent gait disturbances were observed in 6 patients (12%) following primary procedures and in 2 out of 7 patients after re-operations, most of them suffering from postherpetic neuralgia. Minor neurological deficits were noted in 9 cases (18%). DREZ lesions revealed to be an effective procedure in patients with pain related to root avulsion and paraplegia. In contrast, it seems to be less successful for painful states due to other plexus lesions or postherpetic neuralgia.

Patient satisfaction and disability after brachial plexus surgery.

OBJECTIVELittle is known about patient satisfaction and disability after brachial plexus surgery. Would patients undergo the procedure again, if they knew the current result beforehand? How do they rate their result and their disability? METHODSOf 319 plexus patients who had undergone surgery between 1995 and 2005, 199 received a 65-item questionnaire. Measurement instruments included a new plexus-specific outcome questionnaire (Ulm Questionnaire) with categories of satisfaction, functionality, pain, comorbidities, and work; and the disability of the arm, shoulder, and hand questionnaire (DASH; scale, 0–100). RESULTSOf 99 returned questionnaires, 70 were returned in a useful form for evaluation. The results of patients with C5–C6 lesions (21 of 70) are as follows: 90% (19 of 21) would undergo surgery again, 95% (20 of 21) were satisfied with the result, and 86% (18 of 21) subjectively improved. The mean DASH score was 41 (standard deviation [SD], 24). The results of patients with C5–C7 lesions (6 of 70) are as follows: 50% (3 of 6) were satisfied and would undergo surgery again, and 67% (4 of 6) improved. The mean DASH score was 46 (SD, 13). The results of patients with C5–T1 lesions (43 of 70) are as follows: 67% (29 of 43) would undergo surgery again, 81% (35 of 42) were satisfied, and 74% (32 of 43) reported improvement. The mean DASH score was 58 (SD, 26). The overall mean DASH score was 52 (SD, 26). Pain since the injury was prevalent in 86% of patients (60 of 70), back pain in 53%, and depression/anxiety in 21%. Fifty-two percent of those who worked before their injury (27 of 53 patients) remained unemployed or incapacitated for work. Forty-five percent of previous workers (24 of 53) returned to their former occupation. Occupational retraining was successful for 70% of patients (16 of 23). The mean duration until return to work was 9 months overall and 5 months for those who returned to their previous occupation. CONCLUSIONEighty-seven percent of patients were satisfied with the results and 83% would undergo the procedure again. Despite a high satisfaction rate, patients remained considerably disabled, and half of the previous workers did not return to work. Occupational retraining is effective.

Iatrogenic Nerve Injuries

As long as humans have been medically treated, unfortunate cases of inadvertent injury to nerves afflicted by the therapist have occurred. Most microsurgically treated iatrogenic nerve injuries occur directly during an operation. Certain nerves are at a higher risk than others, and certain procedures and regions of the body are more prone to sustaining nerve injury. A high degree of insecurity regarding the proper measures to take can be observed among medical practitioners. A major limiting factor in successful treatment is delayed referral for evaluation and reconstructive surgery. This article on iatrogenic nerve injuries intends to focus on relevant aspects of management from a nerve surgeons perspective.

Accuracy of pedicle screw insertion in the cervical spine for internal fixation using frameless stereotactic guidance

OBJECT Although transpedicular fixation is a biomechanically superior technique, it is not routinely used in the cervical spine. The risk of neurovascular injury in this region is considered high because the diameter of cervical pedicles is very small and their angle of insertion into the vertebral body varies. This study was conducted to analyze the clinical accuracy of stereotactically guided transpedicular screw insertion into the cervical spine. METHODS Twenty-seven patients underwent posterior stabilization of the cervical spine for degenerative instability resulting from myelopathy, fracture/dislocation, tumor, rheumatoid arthritis, and pyogenic spondylitis. Fixation included 1-6 motion segments (mean 2.2 segments). Transpedicular screws (3.5-mm diameter) were placed using 1 of 2 computer-assisted guidance systems and lateral fluoroscopic control. The intraoperative mean deviation of frameless stereotaxy was < 1.9 mm for all procedures. RESULTS No neurovascular complications resulted from screw insertion. Postoperative computed tomography (CT) scans revealed satisfactory positioning in 104 (90%) of 116 cervical pedicles and in all 12 thoracic pedicles. A noncritical lateral or inferior cortical breach was seen with 7 screws (6%). Critical malplacement (4%) was always lateral: 5 screws encroached into the vertebral artery foramen by 40-60% of its diameter; Doppler sonographic controls revealed no vascular compromise. Screw malplacement was mostly due to a small pedicle diameter that required a steep trajectory angle, which could not be achieved because of anatomical limitation in the exposure of the surgical field. CONCLUSIONS Despite the use of frameless stereotaxy, there remains some risk of critical transpedicular screw malpositioning in the subaxial cervical spine. Results may be improved by the use of intraoperative CT scanning and navigated percutaneous screw insertion, which allow optimization of the transpedicular trajectory.

Value of nerve action potentials in the surgical management of traumatic nerve lesions.

OBJECTIVE The goals of the study were to investigate the value of intraoperative electrically evoked nerve action potentials (NAPs) in the surgical treatment of traumatic peripheral nerve injuries (nerve lesions in continuity). METHODS Sixty-four patients with 76 traumatic nerve lesions in continuity were investigated intraoperatively by stimulating and recording NAP from the whole nerve across the suspected lesion site. Among the 76 nerves (nerve lesions) were 43 with incomplete and 33 with complete loss of function. In cases (nerves) with complete loss of function (n = 33), the surgical procedure (external neurolysis, internal neurolysis, or nerve repair) was performed according to the microscopic aspect of the nerve and the result of the intraoperative electrophysiological testing. In cases (nerves) with incomplete loss of function (n = 43), the surgical procedure was performed solely according to the microscopic aspect of the nerve and independently from the result of the intraoperative electrophysiological testing. RESULTS Of 43 nerves with incomplete loss of function, we were able to record reproducible NAPs in 41 (95%) across the lesion site, thus demonstrating a high reliability of the method. Of 33 nerves with complete loss of function, a reproducible NAP could be recorded only in 3. Assuming an axonotmetic lesion in regeneration, we did nothing else on the nerve with excellent clinical results (full recovery). Of the remaining nerves with no NAP, 24 showed a caliber shift of the nerve (in 20 cases a thickening of the nerve, suggesting a neuroma in continuity). A grafting procedure was performed, and the histological evaluation revealed a neurotmetic lesion. However, in six patients with no NAP, there was no clear caliber shift of the nerve. The epineurium was opened and an internal neurolysis performed showing fascicles in continuity. Three patients had good and three had partial (but useful) recovery. CONCLUSIONS In nerve lesions in continuity with complete loss of nerve function, intraoperative NAPs are able to detect axonotmetic lesions in regeneration. Thus, unnecessary further surgical procedures can be avoided. On the other end of the spectrum, no recordable NAP together with a caliber shift of the nerve (suggesting a neuroma in continuity) may facilitate the surgeons decision for a grafting procedure without a time-consuming internal neurolysis. But there is also evidence from our data that not every nerve lesion in continuity without a NAP needs to be grafted.