Citations

OBJECTIVE Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1–L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non–tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257–5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132–4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916–4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009–0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.

OBJECTIVE The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. METHODS A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors’ institution between 1990 and 2022. RESULTS A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18–79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36–62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1–8), and the median (IQR) time to the first recurrence was 29 (9–51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0–245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54–82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038–0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01–1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11–51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. CONCLUSIONS Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

Abstract Background Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. Objective Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. Methods We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. Discussion The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Abstract Objective Advanced Parkinson's Disease (PD) is associated with Parkinson’s Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. Methods We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. Results Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests. Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. Conclusions Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.

Abstract Objective Randomized trials have demonstrated efficacy of spinal cord stimulation (SCS) for treatment of painful diabetic neuropathy (PDN). Preliminary data suggested that treatment of PDN with high-frequency SCS resulted in improvements on neurological examination. The purpose of the present study was to explore whether patients with PDN treated with high-frequency SCS would have improvements in lower-extremity peripheral nerve function. Design Prospective cohort study in an outpatient clinical practice at a tertiary care center. Methods Patients with PDN were treated with high-frequency SCS and followed up for 12 months after SCS implantation with clinical outcomes assessments of pain intensity, neuropathic symptoms, and neurological function. Small-fiber sudomotor function was assessed with the quantitative sudomotor axon reflex test (QSART), and large-fiber function was assessed with nerve conduction studies (NCS). Lower-extremity perfusion was assessed with laser Doppler flowmetry. Results Nine patients completed 12-month follow-up visits and were observed to have improvements in lower-extremity pain, weakness, and positive sensory symptoms. Neuropathy impairment scores were improved, and 2 patients had recovery of sensory responses on NCS. A reduction in sweat volume on QSART was observed in the proximal leg but not at other sites. No significant differences were noted in lower-extremity perfusion or NCS as compared with baseline. Conclusions The improvement in pain relief was concordant with improvement in neuropathy symptoms. The findings from this study provide encouraging preliminary data in support of the hypothesis of a positive effect of SCS on peripheral neuropathy, but the findings are based on small numbers and require further evaluation. Trial registration ClinicalTrials.gov ID NCT03769675.