Local Field Potential-Based Programming: A Proof-of-Concept Pilot Study.

OBJECTIVES: Programming deep brain stimulation (DBS) is still based on a trial-and-error approach, often becoming a time-consuming process for both treating physicians and patients. Several strategies have been proposed to streamline DBS programming, most of which are preliminary and mainly address Parkinson's disease, a condition readily responsive to DBS adjustments. In the present proof-of-principle pilot study, we successfully demonstrate that local field potential (LFP)-based programming can be an effective approach when used for DBS indications that have a delayed temporal onset of benefit. MATERIALS AND METHODS: A recently commercialized implantable pulse generator (IPG) with the capability to non-invasively and chronically stream live and/or record LFPs from a DBS electrode after implantation was used to program one pediatric patient with generalized dystonia and an adult with seizures refractory to multiple medications and vagal nerve stimulation. RESULTS: The IPG survey function detected a peak in the delta range (1.95 Hz) in the left globus pallidus of the first patient. This LFP was detected when recording in the brain area adjacent to contacts 9 and 10 and absent when recording from other areas. The chronic recording of the 1.95 Hz LFP with two sets of stimulation showed a greater power increase with the settings associated with a worsening of dystonia. Broadband LFP home recording of "absence seizure" and "focal/partial seizure" was used in the second patient and reviewer with the IPG "timeline" and "event" functions. The chronic recording of the 2.93 Hz and 8.79 Hz (spit sensing) showed a reduced power with the stimulation setting associated with seizure control. CONCLUSIONS: The approach presented in this pilot proof-of-concept study may inform and streamline the DBS programming for conditions requiring clinicians and patients to wait weeks before appreciating any clinical benefit. Prospective studies on larger samples of patients are warranted.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease.

BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown. CASE PRESENTATION: We present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter. CONCLUSIONS: These findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

Minimally Invasive Placement of Spinal Cord Stimulator Paddle Electrodes Is Associated With Improved Perioperative and Long-Term Experience Among Neuropathic Pain Patients.

STUDY DESIGN: Prospective, observational cohort study. OBJECTIVE: This study compared in-hospital and long-term outcomes among spinal cord stimulation (SCS) patients undergoing paddle insertion by open or minimally invasive surgery (MIS) approaches. SUMMARY OF BACKGROUND DATA: Patients with treatment-refractory extremity neuropathic pain may benefit from SCS. Conventional placement of surgical paddles for an external neurostimulation trial is through open laminectomy, but MIS techniques may offer advantages. METHODS: Twenty SCS patients were prospectively assessed. Open patients underwent caudal thoracic laminectomy for multicolumnar electrode paddle placement. MIS patients underwent paddle placement through interlaminar flavectomy using tubular retractors. Demographic data included age, sex, underlying diagnosis, and preoperative visual analog scale (VAS) extremity scores. Intraoperative data included operative duration, blood loss, and number of device passages to achieve final position. Perioperative data included VAS back pain scores; trial data included time-to-trial and time-to-decision. Postoperative data included 1 month VAS back pain scores and 1 year follow-up device complications. RESULTS: No demographic differences were observed among surgical cohorts. MIS procedures had shorter operative duration (P = 0.03), less blood loss (P < 0.001), and similar median number of device passages (2 vs 1.5, P = 0.71). MIS patients reported less perioperative surgical back pain (P < 0.05). External neurostimulation trials began sooner among MIS patients who also made sooner decision whether to implant the SCS device (2.8 ±â€Š1.4 vs 4.3 ±â€Š1.0 days, P = 0.013). Similar 1 month back pain scores were reported between surgical cohorts (P = 0.08). CONCLUSION: MIS techniques for SCS surgical paddle implantation is associated with less perioperative morbidity and surgical site back pain, shorter external neurostimulator trial duration, and long-term device stability benefits. LEVEL OF EVIDENCE: 2.

Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain.

BACKGROUND: The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients. OBJECTIVE: To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain. METHODS: Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP. RESULTS: Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels. CONCLUSION: Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery.

High Rates of Undiagnosed Psychological Distress Exist in a Referral Population for Spinal Cord Stimulation in the Management of Chronic Pain.

BACKGROUND: Neuropathic pain affects various dimensions of patient health including physical, psychological, and socioeconomic. The spectrum of psychological dysfunction that accompanies this pain phenotype is unknown, as well as differences based on the etiology of the pain among patients referred for spinal cord stimulation (SCS). METHODS: We prospectively assessed SCS referral patients with neuropathic pain for features of psychological distress, either mood or anxiety. Demographic data included age, gender, diagnosis, marital status, and educational level. Screening tools were applied for neuropathic pain (Douleur Neuropathic Quatre and Leeds Assessment of Neuropathic Symptoms and Signs) and psychological distress (Beck Depression Inventory [BDI] and Beck Anxiety Inventory [BAI]). Descriptive statistics defined disease prevalence, compared by gender and diagnosis. Logistic regression correlated pain intensity with severity of psychopathology. RESULTS: Among 150 patients with suitable neuropathic pain diagnoses and no treatable structural pathology, 57% were women, median age was 54 years, and 35% and 42% admitted to routine smoking and alcohol use, respectively. The most common diagnoses were complex regional pain syndrome (46%) and failed back surgery syndrome (38%). Depression symptoms were screened positive by BDI in 63% of patients, and anxiety symptoms were screened positive by BAI in 23% of patients. Pain intensity correlated with BDI scores (p < 0.02) but not BAI scores (p = 0.43). CONCLUSION: The high frequency of depressive and anxiety symptoms screened by the Beck scores in this cohort is an order of magnitude higher than seen in the general population. That many of these cases are undiagnosed should motivate clinicians from primary care providers, comprehensive pain specialists, and surgeons to screen SCS patients for such psychopathology. This represents an opportunity to enhance overall pain management as well as success with invasive neuromodulation strategies.