Thomas Kretschmer

Clinical Article Accumulation of PN1 and PN3 Sodium Channels in Painful Human Neuroma-Evidence from Immunocytochemistry

Summary.Summary. Background: The axolemmal distribution and density of voltage-gated sodium channels largely determines the electrical excitability of sprouting neurites. Recent evidence suggests that accumulation of sodium channels at injured axonal tips may be responsible for ectopic axonal hyperexcitability and the resulting abnormal sensory phenomena of pain and paresthesias. For future improvement in pain management it is necessary to identify structurally significant generators of autorhythmicity. A first step in this regard will be to determine the predominant types of sodium channels in injured axons. The opportunity to test human specimens from painful and non-painful neuroma is of great value. Methods: We employed immunocytochemical methods to investigate if two types of highly specific voltage-gated sodium channel subtypes could be detected in sections of human neuroma. Findings: Both subtypes of sodium channels PN1 and PN3 accumulated abnormally in human neuromas. The immunoreactive pattern was more pronounced in painful neuromas. This is in contrast to previous reports that focused either on PN1 or PN3 as main generators of hyperexcitability induced pain. Interpretation: Both, PN1 and PN3 seem to be involved in hyperexcitability induced pain. It can be expected that a variety of other highly specific voltage gated sodium channel subtypes will be detected in regenerating peripheral nerve in the near future, which contribute to the development of neuropathic pain states. Thus, in order to therapeutically control hyperexcitability induced neuropathic pain, it might be worthwhile to develop pharmaceuticals that can selectively block different sodium channel subtypes and subunits. A review of the role of sodium channels in neuropathic pain is implemented in the discussion.

Surgical Management and Results of 135 Tibial Nerve Lesions at the Louisiana State University Health Sciences Center

OBJECTIVEThis retrospective study presents 33 years of clinical and surgical experience with 135 tibial nerve lesions to review operative techniques and their results and to provide management guidelines for the proper selection of surgical candidates. METHODSBetween 1967 and 1999, 135 patients with tibial nerve lesions at the knee level or below were managed surgically at the Louisiana State University Health Sciences Center. We reviewed these cases. RESULTSOf the 135 cases, traumatic injury accounted for 71, tarsal tunnel syndrome for 46, and nerve sheath tumor for 18. Of 22 lesions not in continuity, functional recovery of Grade 3 or better was achieved in 4 (67%) of 6 patients who required end-to-end suture repair and 11 (69%) of 16 patients who required graft repair. One hundred thirteen tibial nerve lesions in continuity underwent primarily external or internal neurolysis or resection of the lesions. A few received end-to-end suture or graft repair. Direct intraoperative recording of nerve action potentials guided case management decisions. Among the 113 patients with lesions in continuity, 76 (81%) of 94 patients receiving neurolysis, 5 (83%) of 6 receiving suture repair, and 11 (85%) of 13 receiving graft repair recovered function to Grade 3 or better. Repair results were best in patients with recordable nerve action potentials treated by external neurolysis. Results were poor in a few patients with very lengthy lesions in continuity and in reoperated patients with tarsal tunnel syndrome. CONCLUSIONSurgical exploration and repair of tibial nerve lesions, including nerve sheath tumors and tarsal tunnel syndromes, achieved excellent outcomes.

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.

Surgical treatment of traumatic peroneal nerve lesions.

OBJECTIVEIn this study, we compare different surgical procedures regarding the functional outcome of traumatic peroneal nerve lesions. METHODSIn a retrospective study, 48 patients with traumatic lesions (17 iatrogenic) of the peroneal nerve were evaluated. Twenty-two patients presented with lesions in continuity displaying regenerative potential by nerve action potential recording. In these cases, surgery was restricted to either external (12÷) or interfascicular neurolysis (10÷). Twenty-two cases had no regenerative potential (10÷) or showed discontinuity (12÷) and thus were reconstructed with autologous sural nerve grafts. In four cases, a reconstructive procedure was intraoperatively abandoned as a result of the large extent of the lesion. RESULTSThirty-six patients with an adequate follow-up period of at least 18 months were included in this study. Among those with external neurolysis, 73% (eight out of 11) showed a good functional outcome, obviating the need for a kick-up foot brace (M ≥ 4). In the interfascicular neurolysis group, 71% (five out of seven) exhibited a similar outcome. In the grafted group, however, only 28% (five out of 18) obtained a functionally useful result dependent on graft length. A graft length under 6 cm3 led to a functionally useful outcome in 44% of patients (four out of nine) compared with 11% (one out of nine) when the graft length was greater than or equal to 6 cm3. In six patients, muscle–tendon transfers were performed, resulting in strong, useful foot lift. CONCLUSIONPeroneal nerve lesions lacking regenerative signs should be explored. A functionally useful result (M ≥4) was achieved in 72% of the patients with either external or internal neurolysis and in 28% of the patients after a nerve graft procedure. Patients in whom nerve surgery failed to reconstitute useful foot lift need to be evaluated for their suitability to undergo a tendon transfer procedure.

Ankyrin G and voltage gated sodium channels colocalize in human neuroma – key proteins of membrane remodeling after axonal injury

We tested if ankyrin G could be detected in human neuroma, if it colocalized with site-specific peripheral nerve sodium channels that accumulate at axon tips of injured nerve, and if there are differences in the distribution of these proteins in non-painful neuroma and painful neuroma tissue vs. normal nerve. Frozen sections from one painful, six non-painful, and three normal nerves were immunocytochemically examined. A double labeling technique with highly specific antibodies against peripheral nerve type 1 (Na(v)1.7), and peripheral nerve type 3 (Na(v)1.8) sodium channels and anti-ankyrin G antibodies detected sodium channels and ankyrin G on the same section, using confocal laser scanning microscopy. Ankyrin G colocalized with both types of sodium channels. Neuroma specimens exhibited considerably larger immunofluorescence for both sodium channels and ankyrin G compared with normal nerve. The painful neuroma presented an even more pronounced immunolabeling in clusters. Findings support results from animal models that link ankyrin G with clustering of sodium channels at axon tips of unmyelinated, sprouting fibers. A common (repair-) mechanism that exists throughout the human nervous system for clustering sodium channels at a high density is assumed. A dysregulation in this membrane remodeling mechanism might be an initial step in a cascade that leads to a painful rather than a non-painful neuroma.

Role of intraoperative neurophysiology in primary surgery for obstetrical brachial plexus palsy (OBPP)

ObjectiveManagement of conducting neuroma-in-continuity in primary surgery for obstetrical brachial plexus palsy (OBPP) is still discussed controversially. We present our experience with intraoperative neurophysiological recordings in the management of lesions in continuity in OBPP.MethodsA series of ten children with lesions in continuity of the upper brachial plexus is presented. Due to recordable compound nerve action potentials (CNAPs) and muscle response to motor stimulation across the neuroma, five children underwent external neurolysis of neuroma only (neurolysis group). Due to lack of recordable CNAPs or muscle response, resection of neuroma and interpositional nerve grafting were performed in another five children (resection and grafting group). Functional recovery after at least 30 months of follow-up was assessed.ResultsThere was a marked difference in functional recovery between the neurolysis and the resection and grafting group. Especially, recovery of shoulder function was disappointing after external neurolysis of conducting neuroma-in-continuity. At the end of follow-up, results of shoulder and elbow function after resection of neuroma followed by interpositional nerve grafting were better without exception.ConclusionIntraoperative neurophysiological recordings face certain difficulties when used in small children with OBPP. Due to overoptimistic assessment of prognosis after intraoperative CNAP recordings and motor stimulation, the functional results after neurolysis of conducting neuroma-in-continuity are disappointing. Resection of neuroma-in-continuity, conducting or not, offers the best opportunity for maximal functional recovery of the compromised upper limb in OBPP. The role of intraoperative neurophysiological techniques should be confined to the diagnosis of root avulsions.

Avoiding Iatrogenic Nerve Injury in Endoscopic Carpal Tunnel Release

In the hands of the inexperienced, endoscopic carpal tunnel release bears a substantial risk for neurovascular injury. For those thoroughly trained in this technique, it is a fast and elegant but also more expensive way to achieve carpal tunnel release. If performed uneventfully, it minimizes trauma and avoids a substantial palmar skin incision. The authors think that some basic considerations are useful to prevent complications. This article focuses on some points that are relevant to the safe use of this technique.

Brain tumour surgery in the vicinity of short-term memory representation – results of neuronavigation using fMRI images

SummaryObjective. Functional information concerning the surrounding brain is mandatory for a good clinical outcome in brain tumour surgery. The value of fMRI to detect the motorcortex and Broca’s area is widely accepted today. If an appropriate paradigm is used, short-term memory areas can be visualized as well. Obviously this information must be integrated into cranial neuronavigation for an appropriate intra-operative use. We report our first experiences with the direct integration of short-term memory fMRI into cranial neuronavigation. Method. From January 2001 to March 2002 14 patients were operated on for intracranial tumours with short-term memory fMRI imaging, using the “two-back-paradigm”. Both pre- and postoperatively, the short-term memory of all patients was tested additionally by a standardized test battery including 16 different verbal and visuo-spatial items. Results. In all 14 patients the general level of working memory capacity was preserved after surgery. The visuo-spatial performance was kept unchanged or deteriorated slightly, the alertness slightly worsened as well, but we found an improvement in verbal test items. Conclusion. The two-back paradigm is able to visualize verbal memory tasks in fMRI. For visuo-spatial items, a new paradigm has to be designed. In contrast to deep seated brain lesions, focal cortical impairments do not lead to obvious and serious memory deficits. Therefore, the aim of gross total tumour removal has to be balanced against the aim of preservation of short-term memory fields. Nevertheless, the knowledge of the localization of cortical short-term memory fields may combine both aims during navigated brain tumour surgery, thus preserving the patient with a better quality of life.