Rory K.J. Murphy

Bioresorbable silicon electronic sensors for the brain

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body’s abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Magnetic resonance imaging-guided focused laser interstitial thermal therapy for subinsular metastatic adenocarcinoma: technical case report.

BACKGROUND AND IMPORTANCE: To describe the novel use of the AutoLITT System (Monteris Medical, Winnipeg, Manitoba, Canada) for focused laser interstitial thermal therapy (LITT) with intraoperative magnetic resonance imaging (MRI) and stereotactic image guidance for the treatment of metastatic adenocarcinoma in the left insula. CLINICAL PRESENTATION: The patient was a 61-year-old right-handed man with a history of metastatic adenocarcinoma of the colon. He had previously undergone resection of multiple lesions, Gamma Knife radiosurgery, and whole-brain radiation. Despite treatment of a left insular tumor, serial imaging revealed that the lesion continued to enlarge. Given the refractory nature of this tumor to radiation and the deep-seated location, the patient elected to undergo LITT treatment. The center of the lesion and entry point on the scalp were identified with STEALTH (Medtronic, Memphis, Tennessee) image-guided navigation. The AXiiiS Stereotactic Miniframe (Monteris Medical) for the LITT system was secured onto the skull, and a trajectory was defined to achieve access to the centroid of the tumor. After a burr hole was made, a gadolinium template probe was inserted into the AXiiiS base. The trajectory was confirmed via an intraoperative MRI, and the LITT probe driver was attached to the base and CO2-cooled, side-firing laser LITT probe. The laser was activated and thermometry images were obtained. Two trajectories, posteromedial and anterolateral, produced satisfactory tumor ablation. CONCLUSION: LITT with intraoperative MRI and stereotactic image guidance is a newly available, minimally invasive, and therapeutically viable technique for the treatment of deep seated brain tumors. ABBREVIATION: LITT, laser interstitial thermal therapy

Management of atypical cranial meningiomas, part 1: predictors of recurrence and the role of adjuvant radiation after gross total resection.

BACKGROUND Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear. OBJECTIVE To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study. METHODS One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression. RESULTS Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/EBRT (P = .8, P > .99). CONCLUSION Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

Management of Atypical Cranial Meningiomas, Part 2: Predictors of Progression and the Role of Adjuvant Radiation After Subtotal Resection.

BACKGROUND The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear. OBJECTIVE To analyze the clinical, histopathological, and radiographic features associated with progression in AM patients after STR. METHODS Fifty-nine primary AMs after STR were examined for predictors of progression, including the impact of SRS and EBRT, in a retrospective cohort study. RESULTS Twenty-seven patients (46%) progressed after STR (median, 30 months). On univariate analysis, spontaneous necrosis positively (hazard ratio = 5.2; P = .006) and adjuvant radiation negatively (hazard ratio = 0.3; P = .009) correlated with progression; on multivariate analysis, only adjuvant radiation remained independently significant (hazard ratio = 0.3; P = .006). SRS and EBRT were associated with greater local control (LC; P = .02) and progression-free survival (P = .007). The 2-, 5-, and 10-year actuarial LC rates after STR vs STR/EBRT were 60%, 34%, and 34% vs 96%, 65%, and 45%. The 2-, 5-, and 10-year actuarial progression-free survival rates after STR vs STR/EBRT were 60%, 30%, and 26% vs 96%, 65%, and 45%. Compared with STR alone, adjuvant radiation therapy significantly improved LC in AMs that lack spontaneous necrosis (P = .003) but did not improve LC in AMs with spontaneous necrosis (P = .6). CONCLUSION Adjuvant SRS or EBRT improved LC of AMs after STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs.

The natural history and clinical presentation of cervical spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) refers to impaired function of the spinal cord caused by degenerative changes of the cervical spine resulting in spinal cord compression. It is the most common disorder in the United States causing dysfunction of the spinal cord. A literature review of the natural history of mild cervical myelopathy is undertaken. Clinical presentation and current concepts of pathophysiology are also discussed. While many patients with mild signs of CSM will stabilize or improve over time with conservative treatment, the clinical course of a specific individual patient cannot be predicted. Asymptomatic patients with cervical stenosis and abnormalities on electrophysiologic studies may be at higher risk for developing myelopathy.

Repair of a median nerve transection injury using multiple nerve transfers, with long-term functional recovery

Complete loss of median nerve motor function is a rare but devastating injury. Loss of median motor hand function and upper-extremity pronation can significantly impact a patients ability to perform many activities of daily living independently. The authors report the long-term follow-up in a case of median nerve motor fiber transection that occurred during an arthroscopic elbow procedure, which was then treated with multiple nerve transfers. Motor reconstruction used the nerves to the supinator and extensor carpi radialis brevis to transfer to the anterior interosseous nerve and pronator. Sensory sensation was restored using the lateral antebrachial cutaneous (LABC) nerve to transfer to a portion of the sensory component of the median nerve, and a second cable of LABC nerve as a direct median nerve sensory graft. The patient ultimately recovered near normal motor function of the median nerve, but had persistent pain symptoms 4 years postinjury.

No additional protection against ventriculitis with prolonged systemic antibiotic prophylaxis for patients treated with antibiotic-coated external ventricular drains

OBJECT External ventricular drains (EVDs) are commonly used for CSF diversion but pose a risk of ventriculitis, with rates varying in frequency from 2% to 45%. Results of studies examining the utility of prolonged systemic antibiotic therapy for the prevention of EVD-related infection have been contradictory, and no study to date has examined whether this approach confers additional benefit in preventing ventriculitis when used in conjunction with antibiotic-coated EVDs (ac-EVDs). METHODS A prospective performance analysis was conducted over 4 years to examine the impact of discontinuing systemic antibiotic prophylaxis after insertion of an ac-EVD on rates of catheter-related ventriculitis. Ventriculitis and other nosocomial infections were ascertained by a qualified infection disease nurse using definitions based on published standards from the Centers for Disease Control and Prevention, comparing the period when patients received systemic antibiotic therapy for the duration of EVD treatment (Period 1) compared with only for the peri-insertion period (Period 2). Costs were analyzed and compared across the 2 time periods. RESULTS Over the 4-year study period, 866 patients were treated with ac-EVDs for a total of 7016 catheter days. There were 8 cases of ventriculitis, for an overall incidence of 0.92%. Rates of ventriculitis did not differ significantly between Period 1 and Period 2 (1.1% vs 0.4%, p = 0.22). The rate of nosocomial infections, however, was significantly higher in Period 1 (2.0% vs 0.0% in Period 2, p = 0.026). Cost savings of

Magnetic Resonance Imaging Biomarker of Axon Loss Reflects Cervical Spondylotic Myelopathy Severity.

162,516 were realized in Period 2 due to decreased drug costs and savings associated with the reduction in nosocomial infections. CONCLUSIONS Prolonged systemic antibiotic therapy following placement of ac-EVDs does not seem to reduce the incidence of catheter-related ventriculitis and was associated with a higher rate of nosocomial infections and increased cost.

Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes.

Study Design. A prospective cohort study. Objective. In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords. Summary of Background Data. A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies. Methods. Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss. Results. Median DBSI-inflammation volume is similar in control (266 &mgr;L) and mild CSM (171 &mgr;L) subjects, with a significant overlap of the middle 50% of observations (quartile 3 – quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 &mgr;L; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10–5 and 2 x 10–4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases. Conclusion. DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 &mgr;L in axon volume. Level of Evidence: 3

Perimesencephalic subarachnoid hemorrhage associated with a painless, pupillary-involving third cranial nerve palsy: Case report and literature review

BACKGROUND Optimal use of stereotactic radiosurgery (SRS) vs external beam radiation therapy (EBRT) for treatment of residual/recurrent atypical meningioma is unclear. OBJECTIVE To analyze features associated with progression after radiation therapy. METHODS Fifty radiation-naive patients who received SRS or EBRT for residual and/or recurrent atypical meningioma were examined for predictors of progression using Cox regression and Kaplan-Meier analyses. RESULTS Thirty-two patients (64%) received adjuvant radiation after subtotal resection, 12 patients (24%) received salvage radiation after progression following subtotal resection, and 6 patients (12%) received salvage radiation after recurrence following gross total resection. Twenty-one patients (42%) received SRS (median 18 Gy), and 7 (33%) had tumor progression. Twenty-nine patients (58%) received EBRT (median 54 Gy), and 13 (45%) had tumor progression. Whereas tumor volume (P = .53), SRS vs EBRT (P = .45), and adjuvant vs salvage (P = .34) were not associated with progression after radiation therapy, spontaneous necrosis (hazard ratio [HR] = 82.3, P < .001), embolization necrosis (HR = 15.6, P = .03), and brain invasion (HR = 3.8, P = .008) predicted progression in univariate and multivariate analyses. Tumors treated with SRS/EBRT had 2- and 5-year actuarial locoregional control rates of 91%/88% and 71%/69%, respectively. Tumors with spontaneous necrosis, embolization necrosis, and no necrosis had 2- and 5-year locoregional control rates of 76%, 92%, and 100% and 36%, 73%, and 100%, respectively (P < .001). CONCLUSION This study suggests that necrosis may be a negative predictor of radiation response regardless of radiation timing or modality. ABBREVIATIONS AM, atypical meningiomaEBRT, external beam radiation therapyGTR, gross total resectionLC, locoregional controlOS, overall survivalPOE, preoperative embolizationRT, radiation therapySRS, stereotactic radiosurgerySTR, subtotal resection.