Hippocampal afterdischarges: differential spread of activity shown by the [14C]deoxyglucose technique.

Differential spread of afterdischarge activity initiated electrically in ventral and dorsal parts of the hippocampal formation was studied by the [14C]deoxyglucose technique in rats. Afterdischarges initiated in either the ventral or dorsal hippocampal formation, without activation of the ventral subicular cortex, increased glucose utilization in the lateral septum. In contrast, afterdischarges initiated by direct activation of the ventral subicular cortex increased glucose utilization in extensive areas of the ipsilateral amygdala, claustrum, hypothalamus, preoptic region, and basal forebrain.

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.

Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats.

Studies of albino rodents have shown that an absence of pigment in the developing optic stalk may alter the position of the first retinal fibers that grow toward the brain, thereby disrupting the gross topographic relationship of fibers in the nerve (Silver and Sapiro: J. Comp. Neurol. 202:521-538, '81). The abnormalities associated with albinism are more extensive in the Siamese cat than-in previously studied species. Therefore, any abnormalities in differentiation of the stalk and axon guidance may be more readily detected. To investigate the guidance and/or misguidance of optic axons, light and electron microscope analyses were made of serial sections through the optic stalk in normally pigmented and Siamese fetal cats. On E20, before axons enter the optic stalk, the only clear morphological distinction between Siamese and normal cats is the distribution of pigment in the stalk. Pigment is found in the dorsal stalk cells of the normal cat for 200 microns from the optic disc. Although the retinal pigment epithelium of the Siamese optic stalk. By E23 axons invade the ventral optic stalk in both strains. Concurrent with the early stages of axonal exit from the retina, there is complete separation of the stalk's dorsal and ventral tiers. As the cleavage occurs, basal lamina invaginates into the zone of separation following along the plane of the old lumen. The ventral stalk fills with axons while the dorsal tier is shed gradually. In contrast, in the Siamese cat, dorsal stalk cells are not sloughed off properly and instead are incorporated ectopically into the nerve. Basal lamina invagination is irregular. Axons do not fill the Siamese stalk symmetrically but enter the region of ectopic cells, which in turn disrupts gross fiber position. Usually, in the mutant, axons originating from the retina temporal to the optic fissure are those that invade the dorsal tier of ectopic cells. The altered position of optic axons in the mutant stalk may provide an explanation for the chiasmatic misrouting of optic axons in this species.

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.

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.

Metabolic influence of the hippocampus on hypothalamus, preoptic and basal forebrain is exerted through amygdalofugal pathways.

The spread of ventral hippocampal afterdischarge activity to nuclei of the basal diencephalon was studied in rats with fornix lesions and combined lesions of the fornix and stria terminalis. The results indicate that a major hippocampal influence on specific hypothalamic, preoptic and basal forebrain structures is conveyed by way of the amygdala's stria terminalis. An additional hippocampal influence on certain basal forebrain nuclei is consistent with projections via the ventral amygdalofugal pathway.

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.

Carpal tunnel syndrome: correlation of magnetic resonance imaging, clinical, electrodiagnostic, and intraoperative findings.

We undertook a prospective study of 43 wrists in 32 patients who had been clinically diagnosed as having carpal tunnel syndrome (study group) and 5 wrists in people who had no symptoms (control group), correlating the clinical, electrodiagnostic, intraoperative, and magnetic resonance imaging (MRI) findings. MRI of the carpal tunnel and thenar eminence was performed, using coronal and axial T1- and T2-weighted, proton density, and short tau inversion recovery sequences. Abnormalities of the median nerve, as revealed by MRI, were found in 43 of 43 (100%) wrists in the study group and in 0 of 5 (0%) wrists in the control group. Increased signal of the median nerve was seen in 41 of 43 (95%) wrists, increased signal of the flexor tendon sheath in 41 of 43 (95%), volar bowing of the flexor retinaculum in 39 of 43 (91%), increased distance between the flexor tendons in 37 of 43 (86%), and abnormal nerve configuration in 28 of 43 (65%). Increased short tau inversion recovery signal of the thenar muscles was found in 5 of 43 (12%) wrists, all of which had undergone severe denervation changes, as revealed by electromyography. Operative release was performed for 27 of 43 (63%) wrists, and follow-up was obtained for 42 of 43 (98%). A good or excellent postoperative outcome resulted for 20 of 27 (74%) patients, a fair outcome for 2 of 27 (7%), and a poor outcome for 4 of 27 (15%), and 1 of 27 (4%) patients was lost to follow-up. For patients undergoing carpal tunnel release whose MRI revealed an abnormal nerve configuration, the outcome was improved, with good or excellent results in 15 of 18 (83%) patients. No association with outcome was seen with median nerve or flexor tendon signal changes, increased interspace between the flexor tendons, or flexor retinaculum bowing. Our results indicate that MRI is a sensitive diagnostic modality that can demonstrate signal and configurational abnormalities of the median nerve in patients diagnosed with carpal tunnel syndrome. Increased signal of the thenar muscles, as revealed by MRI, using short tau inversion recovery sequences, occurs only in muscles that have undergone severe denervation changes, as revealed by electromyography.

Ulnar nerve entrapment at the elbow: correlation of magnetic resonance imaging, clinical, electrodiagnostic, and intraoperative findings.

The diagnosis of ulnar nerve entrapment at the elbow has relied primarily on clinical and electrodiagnostic findings. Recently, magnetic resonance imaging (MRI) has been used in the evaluation of peripheral nerve entrapment disorders to document signal and configuration changes in nerves. We performed a prospective study on a population of 31 elbows in 27 patients with ulnar nerve entrapment at the elbow. The study correlated MRI findings with clinical, electrodiagnostic, and operative findings. A control population consisting of 10 asymptomatic subjects also was studied by MRI. Electrodiagnostic evaluation confirmed ulnar neuropathy in 24 (77%) elbows of the 31, with localization to the elbow region in 21 (68%). MRI, using a short tau inversion recovery sequence, demonstrated increased signal of the ulnar nerve in 30 (97%) elbows of the 31 and enlargement of the ulnar nerve in 23 (74%). No MRI abnormalities were found in the control population. MRI signal increase of the ulnar nerve occurred an average of 27 mm proximal to the distal humerus and extended distally an average of 4 mm below the distal humerus. The mean total length of increased ulnar nerve signal was 34 mm. Ulnar nerve enlargement occurred an average of 19 mm proximal to the distal humerus and extended distally an average of 8 mm above the distal humerus. The mean total length of ulnar nerve enlargement was 12 mm. The 12 patients who underwent a surgical procedure for ulnar nerve entrapment were found to have ulnar nerve compression, with 9 (75%) having excellent and 3 (25%) having good postoperative results. In this study, MRI was both sensitive and specific in diagnosing ulnar nerve entrapment at the elbow as defined by clinical, electrodiagnostic, and operative findings.

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.

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.

Magnetic resonance neurography for cervical radiculopathy: a preliminary report.

Magnetic resonance neurography was used to directly image cervical spinal nerves in patients with clinical and radiographic evidence of cervical radiculopathy. A magnetic resonance imaging phased-array coil system was used to obtain high-resolution coronal T1-weighted spin echo, coronal/axial T2-weighted fast spin echo with fat saturation, and coronal/axial fast short tau inversion recovery weighted images of the cervical spine and spinal nerves. Three patients with neck and upper extremity pain and one asymptomatic volunteer were studied. The T2-weighted and the fast short tau inversion recovery images demonstrated markedly increased signal in the proximal portion of the affected spinal nerves. In two patients, contrast-to-noise measurements of the affected spinal nerves showed a markedly increased intensity compared with that of the noninvolved spinal nerves. Our findings demonstrate that phased-array coils used in conjunction with magnetic resonance neurography sequences can detect signal abnormalities within compressed cervical spinal nerves in patients with corresponding radicular symptoms and findings. This technique may prove to be helpful in evaluating patients with multilevel disc and/or spondylotic disease of the cervical spine.

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.

Magnetic resonance imaging signal changes in denervated muscles after peripheral nerve injury.

The evaluation of peripheral nerve disorders has traditionally relied on a clinical history, physical examination, and electrodiagnostic studies. Recent studies have used magnetic resonance imaging (MRI) to evaluate a variety of both nerve and muscle disorders. In this article, we describe the use of MRI, using short-tau inversion recovery (STIR) sequences, to evaluate muscle signal characteristics in a variety of peripheral nerve disorders. A total of 32 patients were studied, and 12 representative cases are discussed in detail. Increased STIR signal in muscle was seen in cases of severe axonotmetic injuries involving the transection of axons producing severe denervation changes on electromyography. The increased STIR signal in denervated muscles was seen as early as 4 days after the onset of clinical symptoms, which is significantly earlier than changes detected on electromyography. The MRI signal changes were reversible when the recovery of motor function occurred as a result of further muscle innervation. In cases of neurapraxic nerve injuries, characterized by conduction block without axonal loss, the STIR signal in muscle was normal. These findings show that MRI using STIR sequences provides a panoramic visual representation of denervated muscles useful in localizing and grading the severity of peripheral nerve injury secondary to either disease or trauma. MRI using STIR sequences may therefore play an important role in the prediction of clinical outcome and the formulation of appropriate therapy early after peripheral nerve injury.

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.

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.

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.

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.

Strategies to promote regeneration and recovery in the injured spinal cord.

The damaged spinal cord has only a limited capacity for anatomical and functional recovery. However, a growing body of experimental work is demonstrating a potential for enhanced axonal regeneration and recovery following injury. Important pathophysiologic processes are discussed, along with strategies designed to improve outcome through the reconstruction of damaged pathways and the modulation of the spinal cord's response to the primary injury.

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.