Biomedical subjects

Rajiv Midha

Publications and source records attributed to Rajiv Midha.

At least 19 recordsLinked to original sources

PubMed2006

Generalized peripheral nerve failure during thoracic spine surgery: a case report.

OBJECTIVE: Intra-operative systemic changes impairing peripheral nerve function are not commonly detected with electrophysiology. This case presentation illustrates how somatosensory evoked potential (SSEP) monitoring can detect global changes in peripheral nerve excitability during spine surgery. METHODS: A posterior thoracic spine fixation was performed on a young male with multiple traumatic injuries. Bilateral tibial nerve SSEPs were intraoperatively recorded, along with the right median nerve SSEP for control. RESULTS: A rapid, progressive loss of tibial and median nerve potentials (followed by cortical SSEP loss) occurred 90 min after anaesthetic induction. Oxygenation and fluid volume were adequate throughout the case, despite mean airway resistance being elevated (33 cmH(2)0) and blood pressure being low (80/45 mmHg). Corresponding to the decrease in peripheral nerve responses was a drop in end-tidal CO(2) partial pressure (PaCO(2)) from 37 to 25 mmHg. Approximately, 100 min later, the peripheral and cortically generated SSEPs recovered in 2 of 3 limbs monitored. On emergence from anesthesia it was clear that the patient had bitten and kinked the endotracheal tube thus increasing the airway resistance. Ventilation difficulties were magnified with the patient's prone position. Post-operatively there were no sensorimotor deficits. CONCLUSIONS: Somatosensory evoked potential monitoring during spine surgery can detect uncommon generalized nerve conduction block, and further alert surgical teams to a systemic impairment. This was discovered to result from a compromised endotracheal tube. This can apply in various monitoring situations, as the changes affecting the SSEPs were not related to surgical manipulation.

Adult↗

PubMed2006

Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system.

Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.

Animals↗

PubMed2005

Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts.

Despite spontaneous sprouting of peripheral axons after transection injury, peripheral regeneration is incomplete and limited to short gaps, even with the use of autograft tissue, which is considered to be the "gold" standard. In an attempt to obviate some of the problems associated with autografts, including limited donor tissue and donor site morbidity, we aimed to synthesize a synthetic nerve guidance channel that would perform as well as the nerve autograft. Given that the patency of the nerve guidance channel is critical for repair, we investigated a series of nerve guidance channel designs where patency and the resulting regenerative capacity were compared in a transected rat sciatic nerve injury model. Three tube designs were compared to autograft tissue: plain, corrugated and coil-reinforced tubes of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate). Of the three designs, the coil-reinforced tubes demonstrated superior performance in terms of patency. By electrophysiology and histomorphometry, the coil-reinforced tubes demonstrated outcomes that were comparable to autografts after both 8 and 16 weeks of implantation. The nerve action potential (NAP) velocity and muscle action potential (MAP) velocity for the coil-reinforced PHEMA-MMA tube was 54.6+/-10.1 and 10.9+/-1.3 m/s, respectively at 16 weeks, which was statistically equivalent to those of the autograft at 37.5+/-7.9 and 11.3+/-2.0 m/s. The axon density in the coil-reinforced tube was 2.16+/-0.61x10(4) axons/mm2, which was statistically similar to that of the autograft of 2.41+/-0.62x10(4) axons/mm2 at 16 weeks. These coil-reinforced tubes demonstrated equivalence to autografts for nerve regeneration, demonstrating the importance of channel design to regenerative capacity and more specifically the impact of patency to regeneration.

Action Potentials↗

PubMed2005

MR properties of excised neural tissue following experimentally induced demyelination.

Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue were measured in vitro using an experimental animal model. A tellurium (Te) diet was applied to weanling rats to induce the demyelination process in the sciatic nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time constants and magnetization transfer (MT) were measured each day after applying the Te diet (up to 7 days) and were found to be substantially different from those of normal nerves. An increase in the average T(1) and T(2) was observed along with a decrease in the MT ratio (MTR) and the quantitative MT parameter M(0B), which describes the semisolid pool of protons. Most of the MR parameters correlated very well with the myelin fraction of neural tissue evaluated by quantitative histopathology. The T(2) relaxation spectrum provided the most efficient quantitative assessment of changes in neural tissue microstructure and its analysis resulted in a powerful tool to distinguish the processes of demyelination and inflammation. In comparison, the MT measurements were less successful.

Animals↗

PubMed2005

Long-term in vivo biomechanical properties and biocompatibility of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits.

Artificial grafts are promising alternatives to nerve grafts for peripheral nerve repair because they obviate the complications and disadvantages associated with autografting such as donor site morbidity and limited tissue availability. We have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their efficacy in vivo. Specifically, we studied the short- and long-term stability and biocompatibility of 12 mm long tubes for the repair of surgically created 10 mm nerve gaps in rat sciatic nerves. Prior to implantation, tubes were analyzed in vitro using a micro-mechanical tester to measure displacement achieved with load applied. These results served as a calibration curve, y = 6.8105 x -0.0073 (R2 = 0.9750, n = 28), for in vivo morphometric tube compression measurements. In vivo, most of the PHEMA-MMA conduits maintained their structural integrity up to 8 weeks, but 29% (4/14) of them collapsed by 16 weeks. Interestingly, the tube wall area of collapsed 16-week tubes was significantly lower than those of patent tubes. Tubes were largely biocompatible; however, a small subset of 16-week tubes displayed signs of chronic inflammation characterized by "finger-like" tissue extensions invading the inner tube aspect, inflammatory cells (some of which were ED1+macrophages) and giant cells. Tubes also demonstrated signs of calcification, which increased from 8 to 16 weeks. To overcome these issues, future nerve conduits will be re-designed to be more robust and biocompatible.

Animals↗

PubMed2005

Measuring pulsatile forces on the human cranium.

The cyclic stresses in the cranium caused by pulsation of the brain play an important role in the design of materials for cranioplasty, as well as craniofacial development. However, these stresses have never been quantified. In this study, the force in the epidural space against the cranium was measured intraoperatively in 10 patients using a miniature force probe. Heart and ventilatory rates computed from the force tracing correlated closely with the corresponding measured values in the patients, confirming that the forces measured were indeed a result of brain pulsation. The mean outward systolic normal and tangential stresses were 54.2 kilo-Pascals (kPa) and 345.4 kPa, respectively. The systolic shear stress was 199.8 kPa. Through mechanotransduction, these stresses play a role in cranial development. The calculated yield stress of a cranioplasty repair was 0.4 MPa, which is within one order of magnitude of the known strength of common calcium-phosphate cements. This indicates a possible relation of these pulsatile forces and occult failure of calcium-phosphate cement cranioplasties through material fatigue.

Adult↗

PubMed2005

Histological and magnetic resonance analysis of sciatic nerves in the tellurium model of neuropathy.

Ingestion of tellurium (Te), a toxic element, produces paralysis of the hind limbs in weanling rats that is due to temporary, segmental demyelination of the sciatic nerves bilaterally. Weanling rats were fed a 1.1% elemental Te diet and sacrificed at various time points for histological and magnetic resonance (MR) analysis of the sciatic nerves. No controls exhibited impairments of the hind limbs, whereas Te-treated animals became progressively impaired with increased Te exposure. Toluidine blue-stained nerve sections of Te-treated animals showed widened endoneurial spaces, disrupted myelin sheaths, swollen Schwann cells, and a few instances of axonal degeneration. Te decreased healthy myelin by 68% and increased percent extracellular matrix by 45% on day 7. MR experiments showed a decrease in the area of the short T2 component, an increase in average T1, and an increase in the position of the intermediate T2 component in Te-treated nerves. The correlation coefficient for healthy myelin and average T1 was 0.88 and that for healthy myelin and the area underneath the short T2 component was 0.77. The area of the short T2 component has been postulated as the best measure of the process of demyelination.

Animals↗

PubMed2005

Regeneration into protected and chronically denervated peripheral nerve stumps.

OBJECTIVE: Delayed repair of peripheral nerve injuries often results in poor motor functional recovery. This may be a result of the deterioration or loss of endoneurial pathways in the distal nerve stump before motor axons can regenerate into the stump. METHODS: Using the rat femoral nerve, we protected distal endoneurial pathways of the saphenous nerve with either cross-suture of the quadriceps motor nerve (Group A) or resuture of the saphenous nerve (Group B) to compare later motor regeneration into the "protected" saphenous nerve pathway to chronic denervation and "unprotected" saphenous nerve (Group C). A total of 60 rats, 20 per group, were operated on. After this protection (or lack thereof) for 8 weeks, the motor branch of the femoral nerve was cut and sutured to the distal saphenous nerve to allow motor regeneration into protected and unprotected saphenous nerve stumps. The quantitative assessment of axonal regeneration was performed after 6 weeks by use of nerve sampling for axon counts and retrogradely labeled motor neuron counts. RESULTS: Significantly more myelinated axons innervated the motor (A) than the sensory (B) and no-protection (C) groups. There were significantly more retrogradely labeled femoral motor neurons in Group A than in the unprotected group (C). CONCLUSION: We conclude that even 2 months of denervation of the distal nerve pathway is deleterious to regeneration and that protection of the pathway improves subsequent reinnervation and regeneration. Moreover, if the desired regeneration is motor, protection of the distal nerve pathway by a motor nerve conditions is better than a sensory nerve.

Animals↗

PubMed2005

Pathological features including apoptosis in subacute posttraumatic ascending myelopathy. Case report and review of the literature.

Subacute posttraumatic ascending myelopathy (SPAM) is a rare disorder that may gradually emerge in the first 1 to 3 weeks after a spinal cord injury and is unrelated to syrinx formation or mechanical instability. In addition to several theories that have been put forth to explain the origin of this syndrome, the authors propose a possible role for apoptosis in the causation and the progression of SPAM. They discuss the various theories that have been proposed thus far, to place the role of apoptosis in perspective and use their case as an illustration.

Adult↗

PubMed2005

Peripheral nerve regeneration through a synthetic hydrogel nerve tube.

PURPOSE: As alternatives to nerve grafts for peripheral nerve repair, we have synthesized 12 mm long poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their regenerative capacity for the repair of surgically-created 10 mm rat sciatic nerve gaps. We compared the in vivo regenerative efficacy of these artificial tubes with the gold standard, the nerve autograft. METHODS: Tubes were assessed in vivo for their ability to support nerve regeneration at 4, 8, and 16 weeks post-implantation by histology, electrophysiology, histomorphometry, and reinnervated lateral gastrocnemius (LG) dry muscle mass. RESULTS: Axonal regeneration within the tubes was observed by 8 weeks, with outcome parameters comparable to autografts. This finding was further supported by the electrophysiological and histomorphometric results. The 16 week tube group had a bimodal response, with 60% of the tubes having a similar response to autografts and the other 40% having significantly lower (p < 0.05) outcome measures in several parameters. CONCLUSIONS: Axonal regeneration in artificial tubes was similar to that in autografts at 8 and 16 weeks, however, a bimodal distribution of regeneration was observed in 16 week tubes.

Action Potentials↗

PubMed2004

Nerve transfers for severe brachial plexus injuries: a review.

Nerve transfer procedures are increasingly performed for repair of severe brachial plexus injury (BPI), in which the proximal spinal nerve roots have been avulsed from the spinal cord. The procedure essentially involves the coaption of a proximal foreign nerve to the distal denervated nerve to reinnervate the latter by the donated axons. Cortical plasticity appears to play an important physiological role in the functional recovery of the reinnervated muscles. The author describes the general principles governing the successful use of nerve transfers. One major goal of this literature review is to provide a comprehensive survey on the numerous intra- and extraplexal nerves that have been used in transfer procedures to repair the brachial plexus. Thus, an emphasis on clinical outcomes is provided throughout. The second major goal is to discuss the role of candidate nerves for transfers in the surgical management of the common severe brachial plexus problems encountered clinically. It is hoped that this review will provide the treating surgeon with an updated list, indications, and expected outcomes involving nerve transfer operations for severe BPIs.

Accessory Nerve↗

PubMed2004

MR properties of excised neural tissue following experimentally induced inflammation.

Changes in the MR parameters of inflamed neural tissue were measured in vitro. Tumor necrosis factor-alpha (TNF-alpha) was injected into rat sciatic nerves to induce inflammation with negligible axonal loss and demyelination. The MR parameters, such as T1/T2 relaxation and magnetization transfer (MT), were measured 2 days after TNF-alpha injection and were found to be substantially different from those of normal nerves. The average T1/T2 relaxation times increased, whereas the MT ratio (MTR) and the quantitative MT parameter M0B (which describes the semisolid pool of protons) decreased. The MR parameters correlated very well with the extracellular volume fraction (EM) of neural tissue evaluated by quantitative histopathology. The multicomponent T2 relaxation was shown to provide the best quantitative assessment of changes in neural tissue microstructure, and allowed us to distinguish between the processes of inflammation and demyelination. In comparison, the MT measurements were less successful due to competing contributions of demyelination and pH-sensitive changes in the MT effect.

Animals↗

PubMed2004

Clinical presentation and physical examination.

The main points to assimilate concerning the presentation of peripheral nerve tumors are their subtle features, few symptoms, and even fewer signs. It is no surprise that most lesions become apparent only when a mass becomes palpable. Pain, paresthesia, and a positive Tinel's sign are sometimes the only features, with the paresthesia being variable and unreliable as a clinical entity. Loss of profound sensory function and motor function is generally a late feature. When patients present with progressive pain and significant sensory and any motor deficits, these signs suggest that a more sinister lesion is present. It cannot be overstressed that the stigmata of neurocutaneous disorders should be sought in all patients with suspected peripheral nerve tumors. Similarly, the presence of such stigmata in a patient presenting with vague paresthetic symptoms in a nerve distribution should make the clinician suspect and investigate for an underlying nerve tumor.

Humans↗

PubMed2004

Synchronous lumbar disc herniation in adult twins. Case report.

OBJECTIVE: To report an unusual case of large synchronous lumbar disc herniation in adult twins. METHODS: Case report and relevant literature review. RESULTS: The authors report a case of adult female monozygotic twins who synchronously presented with huge lumbar disc herniation. Rather than being a curious coincidence, this case highlights the potential importance of hereditary factors in the causation of lumbar disc degeneration. The relevant literature regarding the role of genetic factors and their relationship to other risk factors in lumbar disc degeneration is reviewed and discussed. CONCLUSION: Synchronous lumbar disc herniation in adult twins is a rare event. It, however, sheds light on the role of genetic factors in disc degeneration.

Diseases in Twins↗

PubMed2004

Peripheral nerve regeneration through guidance tubes.

Biological nerve grafts have been extensively utilized in the past to repair peripheral nerve injuries. More recently, the use of synthetic guidance tubes in repairing these injuries has gained in popularity. This review focuses on artificial conduits, nerve regeneration through them, and an account of various synthetic materials that comprise these tubes in experimental animal and clinical trials. It also lists and describes several biomaterial considerations one should regard when designing, developing, and manufacturing potential guidance channel candidates. In the future, it it likely that the most successful synthetic nerve conduit will be one that has been fabricated with some of these strategies in mind.

Animals↗

PubMed2004

Chemokine expression in nerve allografts.

OBJECTIVE: Chemokines (chemoattractant cytokines) play a major role in trafficking of cells to areas of inflammation. Infiltration of allograft tissues by immunocompetent cells is critical for rejection of donor tissues. The role of chemokines in nerve allograft rejection is not clear. We hypothesized that chemokines are responsible for attracting macrophages and T lymphocytes into nerve allograft tissue, initiating the graft rejection process. METHODS: Lewis rats received 4-cm-long peroneal nerve allografts and isografts from ACI and Lewis rats, respectively. Twelve hours to 10 days after transplantation, grafts were removed and total cellular ribonucleic acid was extracted. Intragraft gene expression of several chemokines (cytokine-induced neutrophil chemoattractant, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1, MIP-1 alpha, and regulated upon activation normal T-cell expressed and secreted [RANTES]) were analyzed by reverse transcription-polymerase chain reaction. RESULTS: The cytokine-induced neutrophil chemoattractant was expressed in allografts and isografts at early time points (12 h to 6 d). Monocyte chemoattractant protein-1 messenger ribonucleic acid expression was similarly high in both isografts and allografts from 12 hours until 8 days after transplantation. MIP-1 alpha, MIP-2, and RANTES were expressed only in allografts. Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1 alpha) chemokines revealed an early onset (12-24 h), a plateau from 1 to 4 days, and expression abruptly declining by Day 6. The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline. CONCLUSION: Induction of specific chemokine genes precedes nerve allograft infiltration by immunocompetent cells. MIP-1 alpha, MIP-2, and RANTES may be responsible for recruiting macrophages, granulocytes, and lymphocytes, respectively, to the rejecting allograft. In future studies, blockade of these specific chemokines or their receptors may prove to delay or prevent nerve allograft rejection.

Animals↗

PubMed2003

Is multicomponent T2 a good measure of myelin content in peripheral nerve?

Multicomponent T(2) relaxation of normal and injured rat sciatic nerve was measured. The T(2) relaxation was multiexponential, indicating the multicompartmental nature of T(2) decay in nerve tissue. The size of the short, observed T(2) component correlated very well with quantitative assessment of myelin using computer-assisted histopathological image analysis of myelin. Specifically, the size of the short T(2) component reflected the processes of myelin loss and remyelination accompanying Wallerian degeneration and regeneration following trauma. However, it represented all myelin present in the sample and did not distinguish between intact myelin and myelin debris. Other changes in T(2) spectra were also observed and could be correlated with axonal loss and inflammation. The study also questions the validity of previously offered interpretations of T(2) spectra of nerve.

Animals↗

PubMed2003

Neurogenic motor evoked potentials: role in brachial plexus surgery. Case report.

Peripheral nerve graft repair after severe brachial plexus injury is futile if there is degeneration of motor fibers in the proximal nerve stump to which the graft must be attached. Traditional intraoperative neurophysiological assessment methods like nerve action potential (NAP) and somatosensory evoked potential (SSEP) monitoring have been used to evaluate proximal nerve stump integrity, but these methods do not allow evaluation of the integrity of motor fibers back to the anterior horn cell. Consequently, the authors used transcranial electrical stimulation and recorded neurogenic motor evoked potentials (MEPs) directly from the brachial plexus in a patient undergoing surgical repair of a complete upper brachial plexus injury (Erb palsy) to assess the functional continuity of motor fibers. In addition, selected elements of the brachial plexus were directly stimulated, and NAPs were recorded. Finally, SSEPs were recorded from the scalp after stimulation of selected elements of the brachial plexus. Neurogenic MEPs were present from the medial cord of the brachial plexus, but not the middle or upper trunk; NAPs were present from the lateral and posterior cords after middle trunk stimulation, but absent after upper trunk stimulation; and SSEPs were present after medial cord stimulation but absent after stimulation of the upper and middle trunks. For the first time, neurogenic MEPs were coupled with NAPs and SSEPs to evaluate successfully the functional status of motor fibers back to the anterior horn cell for accurate localization of the lesion sites.

Action Potentials↗