Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

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.

Spinal cord stimulation for gait impairment in Parkinson Disease: scoping review and mechanistic considerations.

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.

Procedural predictors of epidural blood patch efficacy in spontaneous intracranial hypotension.

BACKGROUND AND OBJECTIVE: Epidural blood patch (EBP) is a safe and effective treatment for spontaneous intracranial hypotension (SIH), but clinical and procedural variables that predict EBP efficacy remain nebulous. METHODS: This study is an institutional review board-approved retrospective case series with dichotomized EBP efficacy defined at 3 months. The study included 202 patients receiving 604 EBPs; iatrogenic cerebrospinal fluid leaks were excluded. RESULTS: Of the EBPs, 473 (78%) were single-level, 349 (58%) lumbar, 75 (12%) bilevel, and 56 (9%) multilevel (≥3 levels). Higher volume (OR 1.64; p<0.0001), bilevel (3.17, 1.91-5.27; p<0.0001), and multilevel (117.3, 28.04-490.67; p<0.0001) EBP strategies predicted greater efficacy. Only volume (1.64, 1.47-1.87; p<0.0001) remained significant in multivariate analysis. Site-directed patches were more effective than non-targeted patches (8.35, 0.97-72.1; p=0.033). Lower thoracic plus lumbar was the most successful bilevel strategy, lasting for a median of 74 (3-187) days. CONCLUSIONS: In this large cohort of EBP in SIH, volume, number of spinal levels injected, and site-directed strategies significantly correlated with greater likelihood of first EBP efficacy. Volume and leak site coverage likely explain the increased efficacy with bilevel and multilevel patches. In patients with cryptogenic leak site, and either moderate disability, negative prognostic brain MRI findings for successful EBP, or failed previous lumbar EBP, a low thoracic plus lumbar bilevel EBP strategy is recommended. Multilevel EBP incorporating transforaminal administration and fibrin glue should be considered in patients refractory to bilevel EBP. An algorithmic approach to treating SIH is proposed.

Lidocaine Patch to Treat Postoperative Tourniquet Pain After Total Knee Replacement: A Case Report.

Intraoperative tourniquet-related pain is well recognized by anesthesiologists, but postoperative tourniquet-related pain has received little attention. We present a patient who underwent a total knee arthroplasty under general anesthesia and an adductor canal nerve block. She complained of intractable thigh pain postoperatively. Lidocaine 5% patches completely resolved her postoperative tourniquet-related pain.

Erythromelalgia: Identification of a corticosteroid-responsive subset.

BACKGROUND: Corticosteroids (CS) may benefit certain patients with erythromelalgia. OBJECTIVES: Our objective was to determine clinical predictors of corticosteroid-responsive erythromelalgia. METHODS: Patients with erythromelalgia who received CS were identified and stratified into corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs), complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs + CSRs). In the study variable analysis, P < .05 was considered statistically significant. RESULTS: The median (interquartile range) age of the 31-patient cohort was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%) were SRs (P = .003; odds ratio [OR] = 0.069 [95% confidence interval {CI}, 0.011-0.431]). Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or infection; P = .007; OR = 12.667 [95% CI, 2-80.142]). SR patients received CS sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS trial (≥200 mg prednisone cumulatively) was administered to 17 (55%) patients, of whom 13 (76%) were SRs (P = .012; OR = 8.125 [95% CI, 1.612-40.752]). LIMITATIONS: This was a retrospective case series. CONCLUSION: An infectious, traumatic, or surgical precipitant and subacute presentation may portend CR erythromelalgia. A transient "golden window" where CS intervention is useful may exist before irreversible nociceptive remodeling and central sensitization occurs.

Dual-Energy CT to Diagnose Pseudoedema in Contrast-Induced Encephalopathy Following Cerebral Angiography.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a syndrome that may be clinically unrecognized and misdiagnosed as cerebral edema. METHODS: Case report and review. RESULTS: A 72-year-old woman was admitted for elective endovascular embolization of a 10-mm left anterior communicating artery aneurysm. One hour post-procedure, she acutely developed global aphasia. Emergent head computed tomography (CT) and computed tomography-angiography (CTA) showed high attenuation of the left hemispheric subarachnoid spaces interpreted as hemispheric edema; emergent magnetic resonance imaging revealed left hemispheric punctate infarcts. At 12 h, she developed right hemiparesis and encephalopathy. Repeat CTA and CT perfusion revealed decreased left hemisphere cerebral blood flow and diminutive caliber of distal left middle cerebral artery territory vasculature. Repeated angiography with intra-arterial verapamil and systemic blood pressure augmentation were performed for presumed vasospasm. At 20 h, head CT was concerning for worsening left hemispheric edema, but dual-energy, iodine-subtracting sequences revealed significant contrast extravasation contributing to the appearance of sulcal effacement but without actual edema. Out of concern for blood-brain barrier breakdown from CIE, pressor augmentation was discontinued and the patient gradually improved to full neurological recovery within 72 h of symptom onset. CONCLUSIONS: Our case is the first known to report the use of dual-energy, iodine-subtracting CT as a diagnostic tool in differentiating between cerebral edema and pseudoedema in CIE.

Characterization of Prostacyclin-associated Leg Pain in Patients with Pulmonary Arterial Hypertension.

RATIONALE: Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. OBJECTIVES: To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. METHODS: At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. MEASUREMENTS AND MAIN RESULTS: Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20-96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14-36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). CONCLUSIONS: Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible "second hits" that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Occipital Neuromodulation: A Surgical Technique with Reduced Complications.

BACKGROUND: Occipital neuromodulation is a promising treatment modality for refractory headache, but lead migration remains a frequent surgical complication. OBJECTIVES: The primary objective was to identify surgical techniques that may minimize adverse events, particularly lead migration. We hypothesized that a surgical technique employing 2-point anchoring of stimulator leads designed to provide a tension-relief loop and the use of ultrasound for lead placement would decrease the complication rate. STUDY DESIGN AND SETTING: A retrospective analysis was performed through electronic medical record chart review in a tertiary referral center. METHODS: Institutional Review Board (IRB) approval was obtained. Eighteen patients had a trial and subsequent permanent occipital nerve stimulator (ONS) implantation between 2004 and 2011 and were included. Adverse events were recorded and efficacy outcome variables analyzed for significance. RESULTS: The cohort was a median (IQR) 45 (37 - 58) in age and 9 (50%) were women. Tension-relief loops placed via a 2-point anchoring technique and ultrasound use for occipital lead placement were evident in 16 (89%) and 13 (72%), respectively. There was one (6%) clinically insignificant lead position change, not definitively a lead migration, which could have been an artifact of fluoroscope positioning. Adverse events included one (6%) battery malfunction, one (6%) lead malfunction, and 2 (12%) post-implantation infections. Following ONS, there were significant reductions in numeric rating scale (NRS) pain scores from a median (IQR) of 9.5 (8.25 - 10) to 2.5 (1 - 4.75) (P < 0.0001), headache days per week from 7 (7 - 7) to 1.5 (0.375 - 1.75) (P = 0.0005), and the number of daily headache medication from 3 (2.25 - 4) to 2.5 (2 - 3.75) (P = 0.0112). LIMITATIONS: Limitations include retrospective study design, investigator bias, and non-standardized intervals of headache burden assessment. CONCLUSIONS: In ONS, utilization of a 2-point anchoring technique with a tension-relief loop may significantly minimize the risk of lead migration, based on the absence of definitive lead migration in our series. Ultrasound use may improve the anatomic accuracy of lead placement with the possibility of improved efficacy. ONS was associated with significantly decreased headache pain, frequency, and medication use. KEY WORDS: Occipital neuromodulation, occipital nerve stimulation, surgical technique, lead migration, tension-relief loop.

Acute Vision Loss Secondary to Epidural Blood Patch: Terson Syndrome.

BACKGROUND AND OBJECTIVES: Lumbar epidural blood patch (EBP) is a commonly used procedure to treat postdural puncture headache. We present a case of vision loss immediately following an EBP. CASE REPORT: A 49-year-old woman with idiopathic intracranial hypertension received an EBP for postdural puncture headache at an outside facility without fluoroscopic guidance and in the seated position. The patient experienced syncope during the procedure as 25 mL of autologous blood was rapidly injected. The patient regained consciousness and described bilateral vision loss. Brain magnetic resonance imaging was negative for hemorrhage. Dilated fundus examination revealed significant, bilateral retinal and vitreous hemorrhage consistent with Terson syndrome. CONCLUSIONS: This patient developed Terson syndrome as an immediate EBP complication. Iatrogenic Terson syndrome has been previously described with epidural space saline and anesthetic injections, but not EBP. Of 11 reported cases, 10 were female, and 9 had complete vision recovery. Previous studies have demonstrated that epidural space injection increases subarachnoid pressure in a volume- and rate-dependent fashion. An abrupt increase in subarachnoid space pressure likely led to retinal hemorrhage by compromising retinal venous drainage. This is the first known case of Terson syndrome caused by EBP. Injectate volume should be minimized, and a slow rate of injection pursued. The anesthesiologist, pain interventionist, and ophthalmologist should be aware of this rare but disabling complication and consider taking extra precautions when consenting patients for EBP with vision compromise or comorbidities concerning for elevated intracranial pressure.

Acutely Trapped Ventricle: Clinical Significance and Benefit from Surgical Decompression.

BACKGROUND: Focal ventricular obstruction--trapped ventricle--results in cerebrospinal fluid accumulation, mass effect and possible clinical deterioration. There are no systematic studies on the benefit of surgical decompression in adults. METHODS: We reviewed patients admitted with acutely trapped ventricle on brain imaging to assess their prognosis and the effect of surgical intervention on 30-day mortality. RESULTS: Of the 392 patients with trapped ventricle, the most common causes were brain tumor (45%), intracerebral hemorrhage (ICH) (20%), and subdural hematoma (SDH) (14%). Lateral ventricle trapping accounted for 97% of cases. Two hundred and twenty-one patients (56%) received a surgical intervention for trapped ventricle or its causes; 126 (83%) were treated with craniotomy, 26 (17%) with craniectomy, 30 (14%) with external ventricular drain (EVD) alone, 23 (10%) with ventriculoperitoneal shunt alone, and 16 (7%) with endoscopic fenestration of the septum pellucidum. Surgical intervention was associated with mortality reduction from 95% (n = 54) to 48% (n = 11) in the ICH group, from 47% (n = 27) to 12% (n = 15) in the tumor group and from 90% (n = 18) to 20% (n = 7) in the SDH group (p < 0.001 for all comparisons). Univariate logistic analysis showed that surgical intervention and tumor etiology were associated with decreased mortality while age, ICH etiology, intraventricular hemorrhage, midline shift, and anticoagulation were associated with increased mortality. On multivariate logistic regression, surgical intervention remained associated with decreased mortality (p < 0.0001; OR 0.20, 95% CI 0.09-0.42). On subgroup analysis of the ICH cohort, surgical intervention was also associated with decreased mortality (p = 0.028). CONCLUSIONS: Neurosurgical intervention for decompression in patients with trapped ventricle can have a measurable beneficial effect on early mortality.