Kissoon, Narayan

CSF-venous fistulas (CVFs) are a common cause of spontaneous intracranial hypotension. These fistulas usually occur without any preceding major trauma, surgery, or other iatrogenic cause. Occasionally, patients have a history of minor trauma, though such cases are usually still considered spontaneous. Little is known about predisposing factors that cause patients to develop spontaneous CVFs. Most patients with CVFs have multiple meningeal diverticula on spine imaging, and fistulas usually arise in association with a diverticulum. In the vast majority of cases, the culprit diverticulum from which the CVF arises is atraumatic in origin, presumably on the spectrum of normal variation in spinal anatomy. Here, we present two cases of CVFs that arose in association with posttraumatic pseudomeningoceles. To our knowledge, this phenomenon has not yet been reported, and it potentially represents a novel etiology for CVFs that furthers understanding of their pathogenesis.

Abstract Objective To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications. Background Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial‐and‐error approach is inefficient. Methods In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow‐up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta‐blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre‐trained a deep neural network, “TabNet,” using 145 variables, then employed TabNet‐embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non‐responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held‐out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance. Results Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta‐blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta‐blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin. Conclusion We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine‐specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible.

Background Cerebrospinal fluid-venous fistulas (CSFVF) are a common cause of spontaneous intracranial hypotension (SIH). Transvenous embolization has emerged as a reliable treatment option. We review the clinical presentation, imaging, and clinical outcomes of 100 consecutive CSFVF patients who underwent embolization over 2 years. Methods Baseline clinical characteristics, imaging findings (including Bern SIH score), technical outcomes, and long-term imaging and clinical outcomes were collected. All patients had at least 3 months of clinical follow-up and had baseline MRI. 99/100 patients underwent follow-up imaging at ≥3 months post-treatment. Results 100 patients were included. Mean imaging and clinical follow-up duration was 8.3±7.7 months and 15.0±6.8 months, respectively. The mean duration of symptoms before embolization was 40.9±52 months. Mean baseline Bern SIH score was 5.9±3.3. The most common baseline symptoms were headache (96 patients), tinnitus (55 patients), and cognitive dysfunction (44 patients). Technical success rate was 100%. Mean post-treatment Bern SIH score was 0.9±1.6 (P<0.0001). Following treatment, 95% of patients reported significant improvement or resolution in symptoms (58 patients reporting resolution and 37 reporting improvement). 5 patients reported no improvement. There were no major procedural or periprocedural complications. 10 patients had minor procedural complications that did not result in any change in management (Onyx emboli, venous perforation). 19 patients had rebound intracranial hypertension requiring acetazolamide therapy. 7 patients had recurrent fistula at the initially treated level. Conclusions Transvenous embolization of CSFVF in SIH patients is safe and effective with a 95% treatment response, significant improvement in imaging outcomes, and a very low rate of complications.

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.

Introduction Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis or management of this condition is, however, currently lacking. This multisociety guidance aims to fill this void and provide practitioners with comprehensive information and patient-centric recommendations to prevent, diagnose and manage patients with PDPH. Methods Based on input from committee members and stakeholders, the committee cochairs developed 10 review questions deemed important for the prevention, diagnosis and management of PDPH. A literature search for each question was performed in MEDLINE (Ovid) on 2 March 2022. The results from each search were imported into separate Covidence projects for deduplication and screening, followed by data extraction. Additional relevant clinical trials, systematic reviews and research studies published through March 2022 were also considered for the development of guidelines and shared with contributors. Each group submitted a structured narrative review along with recommendations graded according to the US Preventative Services Task Force grading of evidence. The interim draft was shared electronically, with each collaborator requested to vote anonymously on each recommendation using two rounds of a modified Delphi approach. Results Based on contemporary evidence and consensus, the multidisciplinary panel generated 50 recommendations to provide guidance regarding risk factors, prevention, diagnosis and management of PDPH, along with their strength and certainty of evidence. After two rounds of voting, we achieved a high level of consensus for all statements and recommendations. Several recommendations had moderate-to-low certainty of evidence. Conclusions These clinical practice guidelines for PDPH provide a framework to improve identification, evaluation and delivery of evidence-based care by physicians performing neuraxial procedures to improve the quality of care and align with patients’ interests. Uncertainty remains regarding best practice for the majority of management approaches for PDPH due to the paucity of evidence. Additionally, opportunities for future research are identified.

Importance Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

Abstract Introduction Restless legs syndrome (RLS) can dramatically impair sleep quality and quality of life. Some patients have insufficient treatment response or intolerance to available pharmacological options. Exploration of novel therapeutic approaches is needed. Methods We report a case of spinal cord stimulation (SCS) providing benefit in RLS. We also performed a scoping review of SCS in RLS with comprehensive literature search of MEDLINE, EMBASE, Cochrane, and Scopus. Results A 77-year-old woman with DM2, OSA (on ASV), depression, familial RLS and iron deficiency with typical RLS symptoms for all of her adult life presented for management in 2000. In 2011 she developed intractable painful peripheral neuropathy and chronic back pain. Levodopa, pramipexole, oral/intravenous iron, gabapentin, pregabalin, tramadol, oxycodone, and methadone were ineffective or poorly tolerated. A 7-day percutaneous SCS trial resulted in RLS symptoms improvement initially by 50%. A Medtronic stimulator with lead placement at T8-T9 was implanted. 6 months later, the patient toggled between a tonic program (2.1-4.6 mA, 200 us, 50 Hz) and a sub-perception, differential target multiplexed program duty-cycled to 1:2 on:off (3.7 mA, 170 us, 300 Hz). She reported 75% improvement in RLS symptoms. Pain improved by 50%. Total daily dose of Oral Morphine Equivalents was reduced from 48.75mg/day to 37.5mg/day, with a stable once daily dose of 400 mg gabapentin at night. Uninterrupted sleep went from 2-5 hours to 6 hours. RLS worsened when the device was off. Our case corroborates the current evidence of benefit of SCS for RLS from the literature. We identified other 16 unique patients from case reports and series who had undergone SCS for RLS. Leads were most often implanted in mid or low thoracic levels. Stimulation waveforms were high frequency in 4 patients, tonic in 3 patients, burst stimulation in 1 patient, and undescribed in the others. All patients had RLS symptom reduction. Comorbid pain was reported in 14 patients, which also improved with SCS. Complication with lead erosion was reported in one case. Conclusion SCS remains a promising therapeutic approach for refractory RLS that deserves further investigation. SCS may reduce hyperexcitability seen in RLS by modulating dysfunctional spinal, subcortical, and cortical networks. Support (if any)