Circadian Features of Cluster Headache and Migraine: A Systematic Review, Meta-analysis, and Genetic Analysis.

BACKGROUND AND OBJECTIVES: Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies. METHODS: A librarian created search criteria in MEDLINE Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Separate from the systematic review/meta-analysis, we performed a genetic analysis for genes with a circadian pattern of expression (clock-controlled genes or CCGs) by cross-referencing genome-wide association studies (GWASs) of headache, a nonhuman primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs). RESULTS: For the systematic review and meta-analysis, 1,513 studies were found, and 72 met the inclusion criteria; for the genetic analysis, we found 16 GWASs, 1 nonhuman primate study, and 16 imaging reviews. For cluster headache behavior, meta-analyses showed a circadian pattern of attacks in 70.5% (3,490/4,953) of participants across 16 studies, with a clear circadian peak between 21:00 and 03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported in cluster headache participants. At the cellular level, cluster headache was associated with core circadian genes CLOCK and REV-ERBα, and 5 of the 9 cluster headache susceptibility genes were CCGs. For migraine behavior, meta-analyses showed a circadian pattern of attacks in 50.1% (2,698/5,385) of participants across 8 studies, with a clear circadian trough between 23:00 and 07:00 and a broad circannual peak between April and October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in participants with migraine and even lower during an attack. At the cellular level, migraine was associated with core circadian genes CK1δ and RORα, and 110 of the 168 migraine susceptibility genes were CCGs. DISCUSSION: Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiologic foundation for circadian-targeted research into these disorders. TRIAL REGISTRATION INFORMATION: The study was registered with PROSPERO (registration number CRD42021234238).

Subanesthetic ketamine in the ambulatory setting for refractory cancer pain: a 6-year retrospective at a cancer center.

Pain is common in advanced cancer is often refractory to standard treatment. Ketamine has shown promise as an effective adjuvant despite conflicting reports. The aim of this retrospective was to analyze the efficacy of subanesthetic ketamine infusion in the ambulatory setting over an extended follow-up period of 3 months for symptoms related to refractory cancer pain. Forty seven patients treated with intravenous ketamine infusion for refractory cancer pain at a tertiary referral cancer center. Patients demonstrated improvement from baseline in worst, mean, current and least pain immediately after treatment (p < 0.05), worst pain 1 month after treatment (p = 0.003), and current pain (p = 0.036) and worst pain (p = 0.002) 3 months after treatment. Symptoms of quality of life were followed 1 month after treatment.

Case Report: Treatment of Refractory Post-Surgical Neuralgia With Erector Spinae Plane Block.

BACKGROUND: Peripheral nerve blocks (PNBs) are used for a wide spectrum of headache and facial pain disorders. The objective of this case report is to highlight the erector spinae plane (ESP) block, which has recently been reported to successfully treat headache. CASE PRESENTATION: A 70-year-old man with a history of mild to moderate headaches, previously ruptured aneurysm, and right pterional craniotomy and clipping of an anterior communicating artery aneurysm presented with exacerbation of chronic post-surgical scalp pain and severe headache with nausea. Results of the physical examination were not consistent with cellulitis of the scalp, complete blood count and chemistry panel results were unremarkable, and imaging revealed an intact aneurysm clip. Given the severe unilateral throbbing pain with associated nausea, he was treated with a variety of migraine abortives and other pain medications without significant relief. ESP block was performed. He tolerated the procedure well without complications. His pain decreased to 2/10 from a baseline of 9 to 10/10 30 minutes after the procedure, and he was pain free the next day. Follow-up revealed a return of his pain 1 to 2 weeks after the procedure, which prompted follow-up with an outpatient pain management specialist. CONCLUSION: PNBs, ESP block in our case, can be a useful modality in managing chronic neuralgiform pain for treatment-refractory patients. It can provide improvement in quality of life and spare the patient from medication side effects. In an inpatient setting, it can decrease length of stay that would otherwise be extended due to a trial of multiple medications until the pain was controlled. PNBs are used for a wide spectrum of headache and facial pain disorders. This case report highlights successful management of chronic neuralgiform pain with the ESP block, which has recently been reported to successfully treat headache. ESP block provided relief to the patient's neuralgiform pain that was refractory to multiple medications, resulting in decreased length of stay, fewer medication side effects, and improved quality of life. It also provided a window for initiation of long-term pain medications.

High prevalence of greater trochanteric pain syndrome among patients presenting to spine clinic for evaluation of degenerative lumbar pathologies.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) is a relatively common diagnosis among the general population. OBJECTIVE: We aim to determine the prevalence of GTPS among patients who presented to the spine clinic. METHODS: Medical records of patients who were evaluated in the spine clinic were reviewed over a 12-month period (4/1/2016 to 3/31/2017). Patient demographics, presenting symptomatology, physical examination findings, presence or absence of GTPS, medical imaging findings, and interventions were recorded analyzed. Statistical analysis was performed using SPSS Statistics 23.0 (Chicago, IL). Statistical significance is defined as p < 0.05. RESULTS: A total of 273 consecutive patients (145 women, 128 men) were evaluated for degenerative lumbar pathologies by a single spine surgeon over the study period. The average patient age was 61.9 years. Overall, there were 138/273 patients (50.5%) with GTPS (Group I), while 135/273 patients (49.5%) did not have GTPS (Group II). There were 73 patients in Group I received trochanteric injection for GTPS treatment and subsequently returned to clinic for follow-up, and there were 36/73 (49.3%) patients reporting improvement in their symptoms after trochanteric injection. There was a statistically significant predilection for presence of GTPS in the female gender (60% vs 32.8%, p = <0.01). There was no statistically significant difference in the prevalence of low back pain, buttock, thigh or groin pain between the two groups. CONCLUSION: GTPS is a very common but often unrecognized or misdiagnosed condition. Accurate diagnosis and differentiation of GTPS from lumbar spinal pathologies are essential in avoiding potential unnecessary spinal procedures.

Accuracy of S2 Alar-Iliac Screw Placement Under Robotic Guidance.

STUDY DESIGN: Case series. OBJECTIVES: To determine the safety and feasibility of S2 alar-iliac (S2AI) screw placement under robotic guidance. SUMMARY OF BACKGROUND DATA: Similar to standard iliac fixation, S2AI screws aid in achieving fixation across the sacropelvic junction and decreasing S1 screw strain. Fortunately, the S2AI technique minimizes prominent instrumentation and the need for offset connectors to the fusion construct. Herein, we present an analysis of the largest series of robotic-guided S2AI screws in the literature without any significant author conflicts of interest with the robotics industry. METHODS: Twenty-three consecutive patients who underwent spinopelvic fixation with 46 S2AI screws under robotic guidance were analyzed from 2015 to 2016. Screws were placed by two senior spine surgeons, along with various fellow or resident surgical assistants, using a proprietary robotic guidance system (Renaissance; Mazor Robotics Ltd., Caesara, Israel). Screw position and accuracy was assessed on intraoperative CT O-arm scans and analyzed using three-dimensional interactive viewing and manipulation of the images. RESULTS: The average caudal angle in the sagittal plane was 31.0° ± 10.0°. The average horizontal angle in the axial plane using the posterior superior iliac spine as a reference was 42.8° ± 6.6°. The average S1 screw to S2AI screw angle was 11.3° ± 9.9°. Two violations of the iliac cortex were noted, with an average breach distance of 7.9 ± 4.8 mm. One breach was posterior (2.2%) and one was anterior (2.2%). The overall robotic S2AI screw accuracy rate was 95.7%. There were no intraoperative neurologic, vascular, or visceral complications related to the placement of the S2AI screws. CONCLUSIONS: Spinopelvic fixation achieved using a bone-mounted miniature robotic-guided S2AI screw insertion technique is safe and reliable. Despite two breaches, no complications related to the placement of the S2AI screws occurred in this series. LEVEL OF EVIDENCE: Level IV, therapeutic.

Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.

OBJECTIVE: Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis. METHODS: We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent. RESULTS: Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive. INTERPRETATION: The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.

Unilateral holohemispheric central nervous system lesions associated with medically refractory epilepsy in the pediatric population: a retrospective series of hemimegalencephaly and Rasmussen's encephalitis.

OBJECT: Cortical malformations and inflammatory encephalopathy are among common etiologies for medically refractory epilepsy in children. On rare occasions, lesions can affect an entire cerebral hemisphere while sparing the other; the 2 processes that can manifest in this manner are hemimegalencephaly (HME) and Rasmussen's encephalitis (RE). Although the clinical course and radiological appearance between the 2 disorders are distinct, there is occasional overlapping pathology between RE and cortical migration disorders. One question that arises from these observations is whether RE and HME, diseases with holohemispheric involvement but apparently different etiologies, have any overlapping characteristics. METHODS: The authors performed a retrospective review of all patients with presumed diagnosis of HME or RE who underwent hemispherectomy at University of California, San Francisco, and reviewed their clinical presentation, imaging, and pathology data. RESULTS: The authors present the clinicopathological features of 14 pediatric patients with unilateral holohemispheric lesions associated with medically refractory epilepsy. Radiological and pathological assessment classified 7 of the patients as having hemimegalencephaly, while the other 7 were diagnosed as having RE. Four of the patients had unusual features suggestive of overlapping developmental and inflammatory (dual) pathology. All patients underwent hemispherectomies. Eight patients (57%) became seizure free (Engel Class I), 5 patients (36%) had rare seizures (Engel Class II), and 1 patient had significant seizure reduction (Engel Class III). CONCLUSIONS: Based on this case series, HME and RE can be distinguished on the basis of their radiological and histological appearance, even though some cases may have overlapping features. Hemispherectomy was effective at eliminating seizures for both HME and RE.

Crimean-Congo hemorrhagic fever infections reported by ProMED.

OBJECTIVE: There are limited sources describing the global burden of emerging diseases. We reviewed the Crimean-Congo hemorrhagic fever virus (CCHFV) infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data by focusing on CCHFV infections. METHODS: Using the keywords "Crimean Congo hemorrhagic fever" and "Crimean Congo" in the ProMED search engine, we reviewed all the information about the news and harvested data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. RESULTS: We identified 383 entries reported between January 1998 and October 2013. A total 3426 infected cases were reported, with 451 fatal cases, giving an overall case fatality rate (CFR) of 13%. Out of 144 cases for which the gender was reported, 97 (67%) were male. Most of the cases were reported from Turkey, followed by Russia, Iran, Pakistan, and Afghanistan. CONCLUSIONS: Case reporting systems such as ProMED are useful to gather information and synthesize knowledge on the emerging infections. Although certain areas need to be improved, ProMED provided good information about Crimean-Congo hemorrhagic fever.