Diffusivity measurements differentiate benign from malignant lesions in patients with peripheral neuropathy or plexopathy.

BACKGROUND AND PURPOSE: Peripheral nerve disorders caused by benign and malignant primary nerve sheath tumors, infiltration or compression of nerves by metastatic disease, and postradiation neuritis demonstrate overlapping features on conventional MR imaging but require vastly different therapeutic approaches. We characterize and compare diffusivities of peripheral nerve lesions in patients undergoing MR neurography for peripheral neuropathy or brachial or lumbosacral plexopathy. MATERIALS AND METHODS: Twenty-three patients, referred for MR neurography at our institution between 2003 and 2009 for a peripheral mononeuropathy or brachial or lumbosacral plexopathy and whose examinations included DWI, received a definitive diagnosis, based on biopsy results or clinical and imaging follow-up, for a masslike or infiltrative peripheral nerve or plexus lesion suspicious for tumor. Mean ADC values were determined within each lesion and compared across 3 groups (benign lesions, malignant lesions, and postradiation changes). RESULTS: Both ANOVA and Kruskal-Wallis tests demonstrated a statistically significant difference in ADC values across the 3 groups (P = .000023, P = .00056, respectively). Post hoc pair-wise comparisons showed that the ADC within malignant tumors differed significantly from that within benign tumors and postradiation changes. ADC within benign tumors and postradiation changes did not differ significantly from each other. CONCLUSIONS: DWI may be highly effective for the differentiation of benign from malignant peripheral nerve masslike or infiltrative lesions.

MR nerve imaging in a prospective cohort of patients with suspected carpal tunnel syndrome.

OBJECTIVES: To evaluate the reliability and diagnostic accuracy of high-resolution MRI of the median nerve in a prospectively assembled cohort of subjects with clinically suspected carpal tunnel syndrome (CTS). METHODS: The authors prospectively identified 120 subjects with clinically suspected CTS from five Seattle-area clinics. All subjects completed a hand-pain diagram and underwent a standardized nerve conduction study (NCS). The reference standard for determining CTS status was a classic or probable hand pain diagram and NCS with a difference >0.3 ms between the 8-cm median and ulnar peak latencies. Readers graded multiple imaging parameters of the MRI on four-point scales. The authors also performed quantitative measurements of both the median nerve and carpal tunnel cross-sectional areas. NCS and MRI were interpreted without knowledge of the other study or the hand pain diagram. RESULTS: Intrareader reliability was substantial to near perfect (kappa = 0.76 to 0.88). Interreader agreement was lower but still substantial (kappa = 0.60 to 0.67). Sensitivity of MRI was greatest for the overall impression of the images (96%) followed by increased median nerve signal (91%); however, specificities were low (33 to 38%). The length of abnormal signal on T2-weighted images was significantly correlated with nerve conduction latency, and median nerve area was larger at the distal radioulnar joint (15.8 vs 11.8 mm(2)) in patients with CTS. A logistic regression model combining these two MR variables had a receiver operating characteristic area under the curve of 0.85. CONCLUSIONS: The reliability of MRI is high but the diagnostic accuracy is only moderate compared with a research-definition reference standard.

Treatment of recurrent peripheral nerve entrapment problems: role of scar formation and its possible treatment.

Surgical management of peripheral nerve entrapment syndromes is usually successful, but the recurrence of symptoms after initial improvement can and does occur. Extraneural fibrosis is one possible cause of recurrent peripheral nerve problems as a result of nerve compression or tethering. Several approaches to prevent extraneural scarring after surgery have been studied, including wrapping the involved nerve with a graft, the application of various chemical compounds, and radiation. ADCON-T/N, an antiscar bioabsorbable gel device was evaluated in a retrospective clinical review. Sixty-seven percent of patients treated with ADCON-T/N after reoperation of a peripheral nerve experienced prolonged clinical improvement compared with 50% of patients who did not receive ADCON-T/N. These preliminary results suggest that ADCON-T/N may prove to be clinically useful in the surgical treatment of peripheral nerve problems. Additional more rigorous clinical studies are necessary, however.

Acceleration of recovery after injury to the peripheral nervous system using ultrasound and other therapeutic modalities.

Taken together, these studies show the promise of various therapeutic modalities for the noninvasive treatment of peripheral nerve injury. Further progress on these promising methods requires determining the biologic mechanisms responsible for the ability of these modalities to enhance peripheral nerve recovery. Necessary investigations include validation or refutation of the hypothesis that these therapies act on various aspects of the natural healing process. Examples include cellular and molecular processes involved in promoting Wallerian degeneration and the rate and specificity of axonal regeneration and remyelination and muscle reinnervation, processes that are distributed between the regenerating nerve itself, the pathway of the regenerating axon, and the target of the regenerating nerve. An increased understanding of the biologic mechanisms underlying the enhancement of peripheral nerve recovery after injury would lend greater insight into the cellular and molecular mechanisms involved in successful nerve regeneration and muscle reinnervation. This increased understanding may also result in clinically beneficial treatments for peripheral nerve disorders.

Magnetic resonance neurography: magnetic resonance imaging of peripheral nerves.

With advances in modern MR imaging, direct MR visualization of many peripheral nerves is now possible. MR nerve imaging can detect and delineate the extent of neural tumors, demonstrate nerve continuity in cases of traumatic injury, and demonstrate abnormal enlargement and abnormal signal in diseased peripheral nerves. This ability to image peripheral nerves has the potential to dramatically change the diagnosis and treatment of peripheral nerve disease. This article describes the techniques for peripheral nerve imaging and provides a brief overview of a broad spectrum of peripheral nerve abnormalities.

Ultrasound accelerates functional recovery after peripheral nerve damage.

OBJECTIVE: Axonal injury in the peripheral nervous system is common, and often it is associated with severe long-term personal and societal costs. The objective of this study is to use an animal model to demonstrate that transcutaneous ultrasound can accelerate recovery from an axonotmetic injury. METHODS: The sciatic nerve of adult male Lewis rats was crushed in the right midthigh to cause complete distal degeneration of axons yet maintain continuity of the nerve. Beginning 3 days after surgery, various transcutaneous ultrasound treatments or sham treatments were applied 3 days per week for 30 days to the crush site of rats that were randomly assigned to two groups. In the preliminary experiments, there were three animals in each ultrasound group and two control animals. In the final experiment, there were 22 animals in the ultrasound group and 20 animals in the control group. Recovery was assessed by use of a toe spread assay to quantify a return to normal foot function in the injured leg. Equipment included a hand-held transducer that emitted continuous-wave ultrasound. The most successful ultrasound protocol had a spatial peak, time-averaged intensity of 0.25 W/cm2 operated at 2.25 MHz for 1 minute per application. RESULTS: Rats subjected to the most successful ultrasound protocol showed a statistically significant acceleration of foot function recovery starting 14 days after injury versus 18 days for the control group. Full recovery by the ultrasound group occurred before full recovery by the control group. CONCLUSION: Transcutaneous ultrasound applied to an animal model of axonotmetic injury accelerated recovery. Future studies should focus on identification of the mechanism(s) by which ultrasound creates this effect, as a prelude to optimization of the protocol, demonstration of its safety, and its eventual application to humans.

The efficacy of radiotherapy as postoperative treatment for desmoid tumors.

PURPOSE: The purpose of this study was to determine if radiotherapy is a beneficial adjuvant treatment after desmoid tumor resection. METHODS AND MATERIALS: A retrospective analysis was performed on 54 patients who underwent surgery without prior radiation at our institution between 1982 and 1998 to remove a desmoid tumor. Thirty-five patients had adjuvant radiation therapy after surgery, and 19 patients had surgery alone without immediate postoperative radiation. Sixteen of the 35 patients who underwent immediate postoperative radiation treatment had at least one prior resection before reoperation at our institution. Recurrence was defined as radiographic increase in tumor size after treatment. Follow-up interval (mean 39 months) and duration of local control were measured from the date of surgery at our institution. Potential prognostic factors for time to tumor progression were analyzed. RESULTS: Adjuvant treatment with radiation was the only significant prognostic factor for local control. The five-year actuarial local control rate was 81% for the 35 patients who underwent radiation in addition to surgery, compared to 53% for the 19 patients who underwent surgery alone (p = 0.018). For the patients who did not receive adjuvant radiation, only younger age at the time of surgery was associated with increased risk of failure (p = 0.035). Gross or microscopic margin status and number of prior operations were not detected as prognostic for local failure. For patients who did receive postoperative radiation, only abdominal location was associated with increased risk of failure (p = 0.0097). CONCLUSION: Radiation treatment as an adjuvant to surgery improved local control over surgery alone. Multiple operations before adjuvant radiation did not decrease the probability of subsequent tumor control. Radiation should be considered as adjuvant therapy to surgery if repeated surgery for a recurrent tumor would be complicated by a significant risk of morbidity.

MR nerve imaging of the wrist and hand.

Peripheral nerve imaging is still in a relatively early phase of development. This article explains a few of the important technical aspects of peripheral nerve imaging and reviews the results of animal experiments that form the foundation for interpreting image results. The clinical discussion focuses on the use of MR imaging for patients with carpal tunnel syndrome, keeping in mind that many aspects of the imaging technique may be applied to other areas. The reliability, diagnostic accuracy, and potential indications for peripheral nerve imaging are discussed.

Modulation of macrophage and microglial responses to axonal injury in the peripheral and central nervous systems.

OBJECTIVE: After axonal injury, macrophages rapidly infiltrate and become activated in the mammalian peripheral nervous system (PNS) but not the central nervous system (CNS). We used the dorsal root pathway to study factors that modulate the response of macrophages to degenerating axons in both the PNS and the CNS. METHODS: Lewis rats underwent transection of dorsal roots (Group 1), stab within the spinal cord (Group II), crush at the dorsal root entry zone (Group III), transection of dorsal roots combined with a CNS lesion (Group IV), or systemic administration of a known activator of macrophages, lipopolysaccharide, alone (Group V) or combined with transection of dorsal roots (Group VI). ED-1 antibody stained for macrophages and activated microglia at 7, 14, and 42 days postinjury. RESULTS: At early time points, Group I demonstrated ED-1 cells in the PNS but not the CNS portion of the degenerating dorsal roots. Group II revealed ED-1 cells near the stab lesion. Group III demonstrated ED-1 cells adjacent to the dorsal root entry zone crush site. Group IV revealed ED-1 cells along both the PNS and the CNS portions of the degenerating dorsal roots when the CNS lesion was placed near the transected roots. Group V demonstrated few ED-1 cells in the PNS and the CNS, whereas Group VI revealed a marked ED-1 cellular response along both the PNS and the CNS portions of the transected dorsal roots. CONCLUSION: Local CNS trauma and systemic administration of lipopolysaccharide can "prime" macrophages/microglia, resulting in an enhanced response to degenerating axons in the CNS. Such priming might prove useful in promoting axonal regeneration.

Evaluation and surgical management of peripheral nerve problems.

OBJECTIVE: To illustrate how an understanding of the basic biological responses of peripheral nerves to injury is important in formulating a rational treatment plan. METHODS: Peripheral nerve anatomy and physiology are described in a context that is relevant to understanding the different grades of peripheral nerve injury. Methods of evaluating and treating peripheral nerve injuries both medically and surgically are reviewed. Relevant scientific studies with potential clinical impact are also discussed. RESULTS: The clinical symptoms, physical findings, and electrodiagnostic and imaging test results relevant to the diagnosis of peripheral nerve problems are reviewed. Conventional and new medical or surgical strategies in the management of peripheral nerve injuries and mass lesions are described. CONCLUSION: The diagnosis and treatment of peripheral nerve injuries follow logically from an understanding of the biological responses of peripheral nerves after injury and during recovery.

Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration.

After peripheral nerve injury, macrophages infiltrate the degenerating nerve and participate in the removal of myelin and axonal debris, in Schwann cell proliferation, and in axonal regeneration. In vitro studies have demonstrated the role serum complement plays in both macrophage invasion and activation during Wallerian degeneration of peripheral nerve. To determine its role in vivo, we depleted serum complement for 1 week in adult Lewis rats, using intravenously administered cobra venom factor. At 1 d after complement depletion the right sciatic nerve was crushed, and the animals were sacrificed 4 and 7 d later. Macrophage identification with ED-1 and CD11a monoclonal antibodies revealed a significant reduction in their recruitment into distal degenerating nerve in complement-depleted animals. Complement depletion also decreased macrophage activation, as indicated by their failure to become large and multivacuolated and their reduced capacity to clear myelin, which was evident at both light and electron microscopic levels. Axonal regeneration was delayed in complement-depleted animals. These findings support a role for serum complement in both the recruitment and activation of macrophages during peripheral nerve degeneration as well as a role for macrophages in promoting axonal regeneration.

MR neurography. MR imaging of peripheral nerves.

Recent advances in MR imaging coupled with specially designed phased-array surface coils are revolutionizing imaging of the peripheral nervous system. Direct visualization of normal-sized major peripheral nerves within the body is now possible. This article describes the appearance of normal peripheral nerves together with imaging characteristics of various types of nerve pathology including traumatic injury, compressive syndromes, and neural tumors. Imaging of the brachial plexus, lumbosacral plexus, carpal tunnel, cubital tunnel, and cervical nerves is illustrated and discussed. MR neurography techniques permit imaging detection of peripheral nervous system pathology that in some cases allow earlier and more accurate diagnosis. It is believed that this will ultimately lead to improved understanding of peripheral nerve pathophysiology that will, in turn, lead to improved treatment.

Mutism in an adult following hypertensive cerebellar hemorrhage: nosological discussion and illustrative case.

Mutism after cerebellar injury has been associated with tumors, hemorrhage, and surgery of midline cerebellar structures. Literature review identified 54 cases, primarily in children after surgical splitting of the inferior vermis. We present a 47-year-old who developed transient mutism after cerebellar hemorrhage. This represents the first report of transient mutism in an adult with neither tumor nor brainstem infarction and documents the importance of cerebellar structures for initiation and production of speech in adulthood. This case further differs from those previous because of the long mute period and the subsequent return of continued ataxic and dysarthric speech.

Brachial plexus: MR imaging with a dedicated phased array of surface coils.

A phased array of surface coils was constructed for magnetic resonance imaging in three different regions in the brachial plexus. Four-coil subsets of the six-coil array were activated at any given time during imaging in three volunteers. An in vivo estimate of the signal-to-noise ratio (S/N) at three locations in the brachial plexus indicated that the phased-array coil provided a signal-to-noise ratio that was three to six times higher than that of the body coil.

Surgical management of superficial siderosis following cervical nerve root avulsion.

Neurosensory hearing loss, ataxia, spastic paraparesis, sphincter dysfunction, somatosensory disturbances, and cognitive effects are associated with superficial siderosis of the central nervous system caused by chronic intrathecal bleeding. We describe superficial siderosis that developed more than a decade following traumatic brachial nerve root avulsion. While cerebrospinal fluid analysis indicated chronic intrathecal bleeding, angiography did not localize a specific source. Surgical intervention that included repair of a meningeal diverticulum and venous cauterization resulted in overall reduction, but not complete elimination, of central nervous system bleeding.

Magnetic resonance neurography of peripheral nerve lesions in the lower extremity.

OBJECTIVE: We describe the clinical application and utility of high-resolution magnetic resonance neurography (MRN) techniques to image the normal fascicular structure of peripheral nerves and its distortion by mass lesions or trauma in the lower extremity. METHODS: MRN images were obtained using a standard 1.5 Tesla magnet and custom built phased-array coils. Patients were imaged using T1-weighted spin echo without and with gadolinium, T2-weighted fast spin echo with fat peripheral nerve tumors (three neurofibromas and one schwannoma), two with intraneural cysts, and three with traumatic peripheral nerve lesions. Six patients with peripheral nerve mass lesions underwent surgery, thereby allowing MRN images to be correlated with intraoperative and pathological findings. RESULTS: Preoperative MRN accurately imaged the normal fascicular anatomy of peripheral nerves and precisely depicted its relation to tumor and cystic lesions. Increased signal on T2-weighted fast spin-echo and short tau inversion recovery fast spin-echo pulse sequences was seen in the peripheral nerve fascicles of patients with clinical and electrodiagnostic evidence of nerve injury. CONCLUSION: MRN proved useful in the preoperative evaluation and planning of surgery in patients with peripheral nerve lesions.

Application of magnetic resonance neurography in the evaluation of patients with peripheral nerve pathology.

Currently, diagnosis and management of disorders involving nerves are generally undertaken without images of the nerves themselves. The authors evaluated whether direct nerve images obtained using the new technique of magnetic resonance (MR) neurography could be used to make clinically important diagnostic distinctions that cannot be readily accomplished using existing methods. The authors obtained T2-weighted fast spin-echo fat-suppressed (chemical shift selection or inversion recovery) and T1-weighted images with planes parallel or transverse to the long axis of nerves using standard or phased-array coils in healthy volunteers and referred patients in 242 sessions. Longitudinal and cross-sectional fascicular images readily distinguished perineural from intraneural masses, thus predicting both resectability and requirement for intraoperative electrophysiological monitoring. Fascicle pattern and longitudinal anatomy firmly identified nerves and thus improved the safety of image-guided procedures. In severe trauma, MR neurography identified nerve discontinuity at the fascicular level preoperatively, thus verifying the need for surgical repair. Direct images readily demonstrated increased diameter in injured nerves and showed the linear extent and time course of image hyperintensity associated with nerve injury. These findings confirm and precisely localize focal nerve compressions, thus avoiding some exploratory surgery and allowing for smaller targeted exposures when surgery is indicated. Direct nerve imaging can demonstrate nerve continuity, distinguish intraneural from perineural masses, and localize nerve compressions prior to surgical exploration. Magnetic resonance neurography can add clinically useful diagnostic information in many situations in which physical examinations, electrodiagnostic tests, and existing image techniques are inconclusive.

Reduction of extraneural scarring by ADCON-T/N after surgical intervention.

The effects of ADCON-T/N (Gliatech, Inc., Cleveland, OH), a carbohydrate polymer gel, on peripheral nerve scarring and regeneration were studied in rodents undergoing three types of surgical intervention. Procedure I involved external neurolysis of the sciatic nerve from surrounding tissues and separation of its tibial and peroneal components. Procedure II involved the addition of an abrasive injury. Procedure III involved transection and suture anastomosis of the tibial component. ADCON-T/N or a control gel was locally applied in a blind fashion. Additional animals received no gel, as a further control. Animals underwent second operations 4 weeks after Procedures I and II and 6 weeks after Procedure III. The surgical sites were evaluated using a numerical grading scheme to assess wound healing, sciatic nerve adherence to surrounding tissues, and separability of its tibial and peroneal components. Animals receiving ADCON-T/N demonstrated reduced nerve adherence to surrounding tissues and enhanced separability of the tibial and peroneal components, compared with animals receiving control gel or no gel. Quantitative histological analysis revealed a statistically significant reduction in the amount of dense scar tissue surrounding nerves treated with ADCON-T/N. No evidence of nerve toxicity caused by ADCON-T/N was noted. Counts of regenerating myelinated axons in animals undergoing nerve transection and suture repair did not statistically differ in treated and untreated animals. In conclusion, ADCON-T/N seems to be both safe and effective in reducing extraneural scar formation after peripheral nerve surgery and local trauma.

Intraoperative ultrasound for monitoring anterior cervical vertebrectomy. Technical note.

The authors describe the use of intraoperative ultrasonography with a small high-frequency (15 mHz) probe for evaluation of the extent of lateral bone removal during anterior cervical vertebrectomy. The relationship of the bone resection margins to the lateral aspect of the spinal cord was visualized. Postoperative computerized tomography scans revealed the extent of bone removal to be similar to that demonstrated by ultrasound. Intraoperative ultrasonography may be useful during anterior cervical surgery to assure adequate decompression of the spinal canal and spinal cord.