Exploring psychedelic-assisted therapy in the treatment of functional seizures: A review of underlying mechanisms and associated brain networks.

Functional seizures (FS), the most common subtype of functional neurological disorder (FND), cause serious neurological disability and significantly impact quality of life. Characterized by episodic disturbances of functioning that resemble epileptic seizures, FS coincide with multiple comorbidities and are treated poorly by existing approaches. Novel treatment approaches are sorely needed. Notably, mounting evidence supports the safety and efficacy of psychedelic-assisted therapy (PAT) for several psychiatric conditions, motivating investigations into whether this efficacy also extends to neurological disorders. Here, we synthesize past empirical findings and frameworks to construct a biopsychosocial mechanistic argument for the potential of PAT as a treatment for FS. In doing so, we highlight FS as a well-defined cohort to further understand the large-scale neural mechanisms underpinning PAT. Our synthesis is guided by a complexity science perspective which we contend can afford unique mechanistic insight into both FS and PAT, as well as help bridge these two domains. We also leverage this perspective to propose a novel analytic roadmap to identify markers of FS diagnostic specificity and treatment success. This endeavor continues the effort to bridge clinical neurology with psychedelic medicine and helps pave the way for a new field of psychedelic neurology.

Persons With Spinal Cord Injury Report Peripherally Dominant Serotonin-Like Syndrome After Use of Serotonergic Psychedelics.

Psychedelic-assisted therapy (PAT) may treat various mental health conditions. Despite its promising therapeutic signal across mental health outcomes, less attention is paid on its potential to provide therapeutic benefits across complex medical situations within rehabilitation medicine. Persons with spinal cord injury (SCI) have a high prevalence of treatment-resistant mental health comorbidities that compound the extent of their physical disability. Reports from online discussion forums suggest that those living with SCI are using psychedelics, though the motivation for their use is unknown. These anecdotal reports describe a consistent phenomenon of neuromuscular and autonomic hypersensitivity to classical serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD). Persons describe intense muscle spasms, sweating, and tremors, with an eventual return to baseline and no reports of worsening of their baseline neurological deficits. The discomfort experienced interferes with the subjective beneficial effects self-reported. This phenomenon has not been described previously in the academic literature. We aim to provide a descriptive review and explanatory theoretical framework hypothesizing this phenomenon as a peripherally dominant serotonin syndrome-like clinical picture-that should be considered as such when persons with SCI are exposed to classical psychedelics. Raising awareness of this syndrome may help our mechanistic understanding of serotonergic psychedelics and stimulate development of treatment protocols permitting persons with SCI to safely tolerate their adverse effects. As PAT transitions from research trials into accepted clinical and decriminalized use, efforts must be made from a harm reduction perspective to understand these adverse events, while also serving as an informed consent process aid if such therapeutic approaches are to be considered for use in persons living with SCI.

Case report: Improvement in refractory functional seizures, depression, and quality of life with ketamine-assisted therapy.

Functional seizures, a primary subtype of functional neurological disorder (FND), are a known cause of serious neurological disability with an increasing awareness of their impact amongst the neuroscience community. Situated at the intersection of neurology and psychiatry, FND is characterized by a range of alterations in motor, sensory or cognitive performance, such as abnormal movements, limb weakness, and dissociative, seizure-like episodes. Functional seizures are known, in part, to have psychological underpinnings; however, the lack of effective and consistent treatment options requires research and novel approaches to better understand the etiology, diagnosis and what constitutes a successful intervention. Ketamine, a selective blocker of the N-methyl-D-aspartate receptor, has a well-established safety and efficacy profile. In recent years, ketamine-assisted therapy has shown increasing potential for treating a broad range of psychiatric conditions, building on its demonstrated rapid-acting antidepressant effects. Here we present a 51-year-old female with refractory daily functional seizures leading to significant disability and a medical history significant for major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). After unsuccessful treatment attempts, the patient underwent a novel protocol with ketamine-assisted therapy. After 3 weeks of ketamine-assisted therapy followed by 20 weeks of intermittent ketamine treatment and ongoing integrative psychotherapy, the patient's seizures were significantly reduced in frequency and severity. She experienced significant improvements in depressive symptoms and functional ability scores. To our knowledge, this is the first reported case describing improvement in functional seizures following ketamine-assisted therapy. While rigorous studies are needed, this case report encourages further investigation of ketamine-assisted therapy for functional seizures and other functional neurological symptoms.

Psychedelics, epilepsy, and seizures: a review.

Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with a past or current history of seizures, leaving a large cohort of epilepsy and non-epilepsy chronic seizure disorder patients without anywhere to turn for psychedelic-assisted therapy. These exclusions were made despite any significant evidence that clinically supervised psychedelic use causes or exacerbates seizures in this population. To date, no clinical trial or preclinical seizure model has demonstrated that psychedelics induce seizures. This review highlights several cases of individuals experiencing seizures or seizure remission following psychedelic use, with the overall trend being that psychedelics are safe for use in a controlled, supervised clinical setting. We also suggest future research directions for this field.

Wait times and patient throughput after the implementation of a novel model of virtual care in an outpatient neurology clinic: A retrospective analysis.

INTRODUCTION: Neurology wait times - from referral to consultation - continue to grow, leading to various adverse effects on patient outcomes. Key elements of virtual care can be leveraged to improve efficiency. This study examines the implementation of a novel virtual care model - Virtual Rapid Access Clinics - at the Neurology Centre of Toronto. The model employs a patient-centred care workflow, involving multidisciplinary staff and online administrative tools that are synthesized to expedite care and maintain quality. METHODS: Virtual Rapid Access Clinic efficacy was studied by determining average wait times and patient throughput, calculated from anonymous data that was extracted from the clinic patient database (n = 1542). Comparative analysis focused on new patient consultations during the 12-month periods prior to (pre-Virtual Rapid Access Clinic, n = 456) and following (post-Virtual Rapid Access Clinic, n = 1086) Virtual Rapid Access Clinic implementation. RESULTS: After Virtual Rapid Access Clinic implementation, there was a mean 15-day wait time reduction, and a monthly average 52-patient increase in patient throughput. Wait time reductions and increased patient throughput were observed in all three Virtual Rapid Access Clinic sub-clinics - epilepsy, headache and concussion. Respectively, average wait times reduced significantly by 26.4 and 18.9 days and insignificantly by 1.1 days; monthly average patient throughputs increased by 235%, 95% and 161%. DISCUSSION: These findings demonstrated that the Virtual Rapid Access Clinic model of care is effective at reducing patient wait times and increasing patient throughput. While the Virtual Rapid Access Clinic presents a feasible model both during and after pandemic restrictions, further research exploring its scalability in other care contexts, potential changes in care quality and efficiency outside of pandemic restrictions must be performed.

Letter to the editor on "Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017, parts 1-3".

We would like to thank authors Reece and Hulse (2022) for their three-part article titled "Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017", in which the authors infer that cannabis use has a causal role in the development of various cancer types. While the authors use reputable datasets and a well-established epidemiological methodology, the authors' conclusion of a causal association is limited due to biases inherent in ecological epidemiological studies. Though the researchers attempt to overcome these biases through validation and statistical manipulations, their approaches are insufficient to create conditions suitable for causal inferencing upon examination. There are also concerns in the practical and conceptual application of the studies' dataset that further question the validity of the authors' inferences. Further research exploring the potential benefits and harm of cannabinoids in the context of cancer must be performed before a distinct relationship can be defined.

Healing of a Chronic Pressure Injury in a Patient Treated With Medical Cannabis for Pain and Sleep Improvement: A Case Report.

BACKGROUND: A small body of evidence suggests medical cannabis may facilitate wound healing, but the exact mechanism of this effect is unclear. PURPOSE: This case report describes a patient with a pressure injury (PI) who received cannabis oil treatment for pain management and sleep improvement. METHODS: A 37-year-old woman with multiminicore disease, scoliosis, short-chain acyl-CoA dehydrogenase deficiency, and epilepsy presented to the Neurology Centre of Toronto with chronic pain and sleep disturbance, including difficulty initiating and maintaining sleep. She also had a 5-year history of a PI between her right iliac crest and right rib cage that had progressively worsened. The patient received a medical cannabis oil protocol that used a combination of cannabidiol and tetrahydrocannabinol. RESULTS: Cannabis oil was effective in treating pain and sleep difficulties. Unexpectedly, during the first 2 weeks of treatment, the PI started to heal and was almost completely closed at the 2-month follow-up. CONCLUSION: Although it is unknown if the observed healing of this refractory PI was indirectly or directly related to the cannabidiol and tetrahydrocannabinol treatment, the potential relationships among pain, sleep disturbance, cannabis treatment, and healing should be explored.

Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood.

OBJECTIVE: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. METHODS: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information. RESULTS: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder. CONCLUSIONS: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent.

MR-guided laser interstitial thermal therapy for pediatric drug-resistant lesional epilepsy.

OBJECTIVE: To report the feasibility, safety, and clinical outcomes of an exploratory study of MR-guided Laser Interstitial Thermal Therapy (MRgLITT) as a minimally invasive surgical procedure for the ablation of epileptogenic foci in children with drug-resistant, lesional epilepsy. METHODS: Retrospective chart review of all MRgLITT procedures at a single tertiary care center. All procedures were performed using a U.S. Food and Drug Administration (FDA)-cleared surgical laser ablation system (Visualase Thermal Therapy System). Predefined clinical and surgical variables were extracted from archived medical records. RESULTS: Seventeen patients underwent 19 MRgLITT procedures from May 2011 to January 2014. Mean age at seizure onset was 7.1 years (range 0.1-14.8 years). Mean age at surgery was 15.3 years (range 5.9-20.6 years). Surgical substrates were mixed but mainly composed of focal cortical dysplasia (n = 11). Complications occurred in four patients. Average length of hospitalization postsurgery was 1.56 days. Mean follow-up was 16.1 months (n = 16; range 3.5-35.9 months). Engel class I outcome was achieved in seven patients (7/17; 41%), Engel class II in one (1/17; 6%), Engel class III in three (3/17; 18%), and Engel class IV in six (6/17; 35%). Three patients (3/8; 38%) with class I and II outcomes and five patients (5/9; 56%) with class III and IV outcomes had at least one prior resection. Fisher's exact test was not statistically significant for the association between Engel class outcome and previous resection (p = 0.64). SIGNIFICANCE: This study provides descriptive results regarding the use of MRgLITT in a mixed population of pediatric, lesional, drug-resistant epilepsy cases. The ability to classify case-specific outcomes and reduce technical complications is anticipated as experience develops. Further multicenter, prospective studies are required to delineate optimal candidates for MRgLITT, and larger cohorts are needed to more accurately define outcome and complication rates.

Investigating the necessity of computed tomographic scans in children with headaches: a retrospective review.

OBJECTIVE: Headaches are a common problem in the pediatric population. In 2002, the American Academy of Neurology (AAN) developed guidelines on neuroimaging for patients presenting with headache. Our objective was to determine the frequency of computed tomographic (CT) scanning ordered by a range of medical practitioners for pediatric patients presenting with primary headache. METHODS: A retrospective chart review was conducted at the Children's Hospital of Eastern Ontario (CHEO), a tertiary care centre in Ontario. One hundred fifty-one records of patients referred to the outpatient neurology clinic at CHEO with ''headache'' or ''migraine'' as the primary complaint from 2004 to 2009 were randomly selected. Ninety-nine patients with normal neurologic examinations were ultimately included. RESULTS: Thirty-four patients (34%; 95% CI 25-45) had undergone CT scanning. None of the 34 CT scans (0%; 95% CI 0-10) showed significant findings, and none changed the headache diagnosis or management. Eleven (32%) of the CT scans were ordered by CHEO neurologists, 15 (44%) by community physicians, and 8 (24%) by CHEO emergency physicians. CONCLUSION: A high proportion of children presenting with primary headaches and a normal neurologic examination undergo CT scanning, despite well-established AAN guidelines regarding neuroimaging. Most of these CT scans do not appear to alter diagnosis and management. A variety of non-evidencebased factors may be encouraging physicians to overinvestigate this population and, as a result, increasing the risk of adverse events due to radiation exposure. Implementing initiatives at a site-based level that promote the use of established guidelines before performing CT scanning in this population may be beneficial.

Web-based software to assist in the localization of neuroanatomical lesions.

OBJECTIVE: To evaluate the educational effectiveness of a novel, web-based neuroanatomical localization application. METHODS: A prototype version of a neuroanatomical localization application was developed, limited to lesions involving Cranial Nerve (CN) VII. Second year medical students at the University of Ottawa were recruited to participate in the study. Participants were exposed to a didactic teaching session on CN VII anatomy. They were subsequently randomized to two groups - one group was granted access to the localization application (the "intervention group"), while the other group was given a booklet of standard textbook resources (the "control group"). Participants then completed a case-based multiple choice test on localization of neurologic lesions associated with CN VII, followed by a questionnaire regarding the experience. RESULTS: Thirty-nine students volunteered to participate. Twenty were randomized to the intervention group and 19 to the control group. There was a mean test score difference of 1.3 (CI.95=0.2, 2.3) that was significantly higher in the intervention group when compared to the control group. Significance was determined by a Wilcoxon rank test (p=0.028). Questionnaire results were similar for both groups, showing an overall favourable evaluation of the localization application. CONCLUSIONS: The results support our hypotheses that students using the application would perform better on the multiple choice question (MCQ) test and there would be an overall preference for its use. The demonstrated educational benefit of the application, in addition to the demand for such a resource expressed by the participants, warrant further investigation into the development of a neurological localization application.

Growth outcomes and complications after radiologic gastrostomy in 120 children.

BACKGROUND: Enteral feeding is ideal for children with low caloric intake. It can be provided through different methods, including nasogastric, nasojejunal, gastrostomy, or gastrojejunostomy tubes. OBJECTIVE: To assess growth outcomes of pediatric patients following retrograde percutaneous gastrostomy (RPG) and compare complications with those following other gastrostomy methods. MATERIALS AND METHODS: We retrospectively reviewed 120 random RPG patients from 2002 to 2003 (mean follow-up, 2.7 years). Patient weights and growth percentiles were recorded at insertion, and at 0-5 months, 6-12 months, and 18-24 months after insertion, and then compared using a Student's t-test. Complications and tube maintenance issues (TMIs) were recorded. RESULTS: Gastrostomy tube insertion was successful in all 120 patients (59 boys, 61 girls; mean age 4.3 years). The most common underlying diagnosis was neurologic disease (29%, 35/120) and the main indication was inadequate caloric intake (24%, 29/120). Significant increases in growth percentile for the entire population were demonstrated between insertion and 0-5 months (18.7-25.3; P<0.001) and between insertion and 18-24 months (18.7-25.8; P<0.001). In boys and girls significant growth increases occurred between insertion and 0-5 months (boys P=0.004; girls P=0.01). There were 11 major postprocedural complications, 100 minor complications and 169 TMIs. CONCLUSION: RPG provides long-term enteral nutrition in the pediatric population and increases growth significantly 6 and 24 months after insertion. Minor complications and TMIs are frequent.