Acute Flaccid Myelitis: Review of Clinical Features, Diagnosis, and Management with Nerve Transfers.

BACKGROUND: Acute flaccid myelitis (AFM) is a devastating neurologic condition in children, manifesting as acute limb weakness and/or paralysis. Despite increased awareness of AFM following initiation of U.S. surveillance in 2014, no treatment consensus exists. The purpose of this systematic review was to summarize the most current knowledge regarding AFM epidemiology, cause, clinical features, diagnosis, and supportive and operative management, including nerve transfer. METHODS: The authors systematically reviewed the literature based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases to search the keywords ("acute flaccid myelitis"), ('acute flaccid myelitis'/exp OR 'acute flaccid myelitis'), and (Acute AND flaccid AND myelitis). Included articles reported on (1) AFM diagnosis and (2) patient-specific data regarding epidemiology, cause, clinical features, diagnostic features, or management of AFM. RESULTS: Ninety-nine articles were included in this review. The precise cause and pathophysiologic mechanism of AFM remain undetermined, but AFM is strongly associated with nonpolio enterovirus infections. Clinical presentation typically comprises preceding viral prodrome, pleocytosis, spinal cord lesions on T2-weighted magnetic resonance imaging, and acute onset of flaccid weakness/paralysis with hyporeflexia in at least one extremity. Supportive care includes medical therapy and rehabilitation. Early studies of nerve transfer for AFM have shown favorable outcomes for patients with persistent weakness. CONCLUSIONS: Supportive care and physical therapy are the foundation of a multidisciplinary approach to managing AFM. For patients with persistent limb weakness, nerve transfer has shown promise for improving function in distal muscle groups. Surgeons must consider potential spontaneous recovery, patient selection, donor nerve availability, recipient nerve appropriateness, and procedure timing.

A customized 3D implant to target laser interstitial thermal therapy ablation of a posterior fossa mass.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique that has been demonstrated to successfully ablate intracranial tumors. While LITT for supratentorial lesions can often be straightforward, ablation of infratentorial lesions can be difficult with current targeting technologies and instrumentation. The anatomical difficulty of targeting posterior fossa masses can be further complicated in patients who have had a prior craniectomy or other procedure that removed the bone that is required to set the surgical trajectory. This article describes use of a three-dimensional (3D)-printed customized surgical implant to improve and enable targeting of posterior fossa lesions using LITT, particularly in the setting of prior craniectomy. A 3D-printed implant was customized for a patient with a history of metastatic lung cancer and prior posterior fossa craniectomy who presented for treatment of a progressively enlarging contrast-enhancing lesion in the right cerebellar hemisphere. The device included a built-in bolt trajectory for LITT ablation. The temporary implant was successfully fabricated for use with laser ablation of a right cerebellar mass. Three potential trajectories for the LITT bolt were incorporated into the temporary implant, but only the primary trajectory was utilized. Laser ablation was performed with the implant and a SideFire laser probe. Customized 3D-printed implants can enable the use of LITT for patients who would not otherwise be candidates.

CT-measured Cortical Volume Ratio Is an Accurate Alternative to Nuclear Medicine Split Scan Ratio Among Living Kidney Donors.

BACKGROUND: The 125I-iothalamate clearance and 99mTc diethylenetriamine-pentaacetic acid (99mTc-DTPA) split scan nuclear medicine studies are used among living kidney donor candidates to determine measured glomerular filtration rate (mGFR) and split scan ratio (SSR). The computerized tomography-derived cortical volume ratio (CVR) is a novel measurement of split kidney function and can be combined with predonation estimated GFR (eGFR) or mGFR to predict postdonation kidney function. Whether predonation SSR predicts postdonation kidney function better than predonation CVR and whether predonation mGFR provides additional information beyond predonation eGFR are unknown. METHODS: We performed a single-center retrospective analysis of 204 patients who underwent kidney donation between June 2015 and March 2019. The primary outcome was 1-y postdonation eGFR. Model bases were created from a measure of predonation kidney function (mGFR or eGFR) multiplied by the proportion that each nondonated kidney contributed to predonation kidney function (SSR or CVR). Multivariable elastic net regression with 1000 repetitions was used to determine the mean and 95% confidence interval of R2, root mean square error (RMSE), and proportion overprediction ≥15 mL/min/1.73 m2 between models. RESULTS: In validation cohorts, eGFR-CVR models performed best (R2, 0.547; RMSE, 9.2 mL/min/1.73 m2, proportion overprediction 3.1%), whereas mGFR-SSR models performed worst (R2, 0.360; RMSE, 10.9 mL/min/1.73 m2, proportion overprediction 7.2%) (P < 0.001 for all comparisons). CONCLUSIONS: These findings suggest that predonation CVR may serve as an acceptable alternative to SSR during donor evaluation and furthermore, that a model based on CVR and predonation eGFR may be superior to other methods.

Sustained stimulation of ß2- and ß3-adrenergic receptors leads to persistent functional pain and neuroinflammation.

Functional pain syndromes, such as fibromyalgia and temporomandibular disorder, are associated with enhanced catecholamine tone and decreased levels of catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines). Consistent with clinical syndromes, our lab has shown that sustained 14-day delivery of the COMT inhibitor OR486 in rodents results in pain at multiple body sites and pain-related volitional behaviors. The onset of COMT-dependent functional pain is mediated by peripheral ß2- and ß3-adrenergic receptors (ß2- and ß3ARs) through the release of the pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Here, we first sought to investigate the role of ß2- and ß3ARs and downstream mediators in the maintenance of persistent functional pain. We then aimed to characterize the resulting persistent inflammation in neural tissues (neuroinflammation), characterized by activated glial cells and phosphorylation of the mitogen-activated protein kinases (MAPKs) p38 and extracellular signal-regulated kinase (ERK). Separate groups of rats were implanted with subcutaneous osmotic mini-pumps to deliver OR486 (15 mg/kg/day) or vehicle for 14 days. The ß2AR antagonist ICI118551 and ß3AR antagonist SR59230A were co-administrated subcutaneously with OR486 or vehicle either on day 0 or day 7. The TNFα inhibitor Etanercept, the p38 inhibitor SB203580, or the ERK inhibitor U0126 were delivered intrathecally following OR486 cessation on day 14. Behavioral responses, pro-inflammatory cytokine levels, glial cell activation, and MAPK phosphorylation were measured over the course of 35 days. Our results demonstrate that systemic delivery of OR486 leads to mechanical hypersensitivity that persists for at least 3 weeks after OR486 cessation. Corresponding increases in spinal TNFα, IL-1ß, and IL-6 levels, microglia and astrocyte activation, and neuronal p38 and ERK phosphorylation were observed on days 14-35. Persistent functional pain was alleviated by systemic delivery of ICI118551 and SR59230A beginning on day 0, but not day 7, and by spinal delivery of Etanercept or SB203580 beginning on day 14. These results suggest that peripheral ß2- and ß3ARs drive persistent COMT-dependent functional pain via increased activation of immune cells and production of pro-inflammatory cytokines, which promote neuroinflammation and nociceptor activation. Thus, therapies that resolve neuroinflammation may prove useful in the management of functional pain syndromes.