Muscae volitantes: A 19th-century precursor of visual snow syndrome?

PURPOSE: Visual snow syndrome comprises a whole-field static-like visual disturbance, with increased awareness of entopic phenomena, an inability to suppress the 'just seen' and photophobia. Visual snow syndrome is often associated with other problems such as headache, tinnitus, and anxiety. The earliest reported case of a patient experiencing symptoms consistent with visual snow syndrome dates only to 1995. This paper seeks to find patterns of experience in the medical literature of the past that are reminiscent of visual snow syndrome, to challenge the view that it is in any sense a novel disorder. Descriptions of subjective visual sensations such as experienced by patients suffering from visual snow syndrome were sought in treatises, textbooks and other literature generated by leading figures in 19th-century ophthalmology, physiology and physics. CONCLUSION: While retrospective diagnosis of modern illness categories in historical medical literature is an enterprise fraught with pitfalls, it is nonetheless possible to see patterns of experience in the 19th-century medical literature that are strongly reminiscent of visual snow syndrome.

Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy-Analysis from the UK Medical Cannabis Registry.

BACKGROUND: There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. METHODS: A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events. RESULTS: Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). CONCLUSION: The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Percutaneous electrical nerve stimulation (PENS) therapy for refractory primary headache disorders: a pilot study.

Purpose: Primary headache disorders are common, but many patients are refractory to medical treatment. Percutaneous electrical nerve stimulation (PENS) therapy involves the stimulation of one or more individual nerves or dermatomes using needle probes. We assessed whether a 'single shot with single probe' strategy would benefit patients with refractory headache disorders, including chronic migraine (CM), and chronic cluster headache (CCH).Materials and methods: Service evaluation of 36 patients treated with PENS therapy between September 2012 and June 2016. Follow-up data were available for 33 patients, of whom 16 had CM, nine had CCH, and six had secondary headache disorders. PENS was given using Algotec® disposable 21 gauge PENS therapy probes (8 cm) to the occipital nerve ipsilateral to the pain (or bilaterally in cases of bilateral pain). Stimulation was delivered at 2 Hz/100 Hz, at 3 cycles/s, between 1.2 and 2.5 V depending on patient tolerability, for 25-28 min.Results: Six of nine patients with CCH improved significantly after the first session. In all patients with CCH, PENS therapy was well tolerated, with no significant adverse events reported. One patient with CCH reverted to episodic cluster. Only four patients with CM experienced any benefit.Conclusion: PENS therapy shows potential as a relatively non-invasive, low-risk, and inexpensive component of the treatment options for refractory primary headache disorders, particularly CCH.

Drug therapy in headache.

All physicians will encounter patients with headaches. Primary headache disorders are common, and often disabling. This paper reviews the principles of drug therapy in headache in adults, focusing on the three commonest disorders presenting in both primary and secondary care: tension-type headache, migraine and cluster headache. The clinical evidence on the basis of which choices can be made between the currently available drug therapies for acute and preventive treatment of these disorders is presented, and information given on the options available for the emergency parenteral treatment of refractory migraine attacks and cluster headache.

Clinical outcome analysis of patients with multiple sclerosis - Analysis from the UK Medical Cannabis Registry.

INTRODUCTION: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR). METHOD: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant. RESULTS: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %). CONCLUSIONS: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.

UK Medical Cannabis Registry: Assessment of clinical outcomes in patients with insomnia.

INTRODUCTION: The primary aim of this study was to assess changes in sleep-specific health-related quality of life (HRQoL) for those prescribed cannabis-based medicinal products (CBMPs) for insomnia. METHODS: A case series of UK patients with insomnia was analyzed. Primary outcomes were changes in the Single-Item Sleep-Quality Scale (SQS), Generalized Anxiety Disorder-7 (GAD-7), and EQ-5D-5L at up to 6 months from baseline. Statistical significance was identified as a p value < .050. RESULTS: 61 patients were included in the analysis. There was an improvement in the SQS from baseline at 1, 3, and 6 months (p < .001). There were also improvements in the EQ-5D-5L Index value and GAD-7 at 1, 3, and 6 months (p < .050). There were 28 (45.9%) adverse events recorded by 8 patients (13.1%). There were no life-threatening/disabling adverse events. CONCLUSION: Patients with insomnia experienced an improvement in sleep quality following the initiation of CBMPs in this medium-term analysis. Fewer than 15% of participants reported one or more adverse events. However, due to the limitations of the study design, further investigation is required before definitive conclusions can be drawn on the efficacy of CBMPs in treating insomnia.

The migraine theories of Liveing and Latham: a reappraisal.

This article discusses the leading 19th century British contributions to theories of migraine pathogenesis: Edward Liveing's theory of nerve storms and Peter Wallwork Latham's vasomotor theory, providing a detailed accounts of their origin, and their rise and fall in the latter decades of the century, emphasizing the central role of William Gowers in their ultimate downfall. The article concludes by discussing the reasons behind the rising reputation of Liveing's work, demonstrating how history may be made to serve contemporary ends.

UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders.

OBJECTIVES: Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research specifically focuses on CBMPs' efficacy and safety in headache disorders. This study aims to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population. METHODS: A case series of the UK Medical Cannabis Registry was conducted. Primary outcomes were changes from baseline in PROMs (Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire and Single-Item Sleep Quality Scale (SQS)) at 1-, 3-, and 6-months follow-up. P-values <0.050 were deemed statistically significant. RESULTS: Ninety-seven patients were identified for inclusion. Improvements in HIT-6, MIDAS, EQ-5D-5L and SQS were observed at 1-, 3-, and 6-months (p < 0.005) follow-up. GAD-7 improved at 1- and 3-months (p < 0.050). Seventeen (17.5%) patients experienced a total of 113 (116.5%) adverse events. CONCLUSION: Improvements in headache/migraine-specific PROMs and general health-related quality of life were associated with the initiation of CBMPs in patients with headache disorders. Cautious interpretation of results is necessary, and randomized control trials are required to ascertain causality.

An observational study of clinical outcome measures in patients treated with cannabis-based medicinal products on the UK Medical Cannabis Registry.

INTRODUCTION: While there is increasing evidence of the effects of cannabis-based medicinal products (CBMPs) on health-related quality of life (HRQoL), a major limitation of the current literature is the heterogeneity of studied CBMPs. This study aims to analyze changes in HRQoL in patients prescribed a homogenous selection of CBMPs. METHODS: Primary outcomes were changes in patient-reported outcomes (PROMs) at 1, 3, 6, and 12 months from baseline. The secondary outcome was an adverse events analysis. Statistical significance was defined as p < 0.050. RESULTS: 1378 patients prescribed Adven® CBMPs (Curaleaf International, Guernsey, UK) were included in the final analysis. 581 (42.16%) participants were current users of cannabis at baseline. 641 (46.51%), 235 (17.05%), and 502 (36.43%) patients were treated with oils, dried flowers, or a combination of the two, respectively. Improvements were found in all PROMs in each route of administration at 1, 3, 6, and 12 months from baseline (p < 0.010). Those prescribed dried flower only or both oils and dried flower experienced greater improvements in GAD-7, SQS, and EQ-5D-5L index values at 12 months (p < 0.050). There was no difference in outcomes between those prescribed dried flower only or dried flower with oils (p > 0.050). 3663 (265.82%) adverse events were reported by 297 (21.55%) patients. CONCLUSION: There was an associated improvement in self-reported anxiety, sleep quality, and HRQoL in patients treated with the CBMPs. Those prescribed treatment formulations including dried flower were most likely to show a clinical improvement. However, these results must be interpreted with caution given the limitations of study design.

An observational study of safety and clinical outcome measures across patient groups in the United Kingdom Medical Cannabis Registry.

BACKGROUND: There is a paucity of high-quality data on patient outcomes and safety after initiating treatment with cannabis-based medicinal products (CBMPs). The aim of this study was to assess the clinical outcomes and safety of CBMPs by analyzing patient-reported outcome measures and adverse events across a broad spectrum of chronic conditions. RESEARCH DESIGN AND METHODS: This study analyzed patients enrolled in the UK Medical Cannabis Registry. Participants completed the EQ-5D-5L to assess health-related quality of life, Generalized Anxiety Disorder-7 (GAD-7) questionnaire to measure anxiety severity, and the Single-item Sleep Quality Scale (SQS) to rate sleep quality at baseline and follow-up after 1, 3, 6, and 12 months. RESULTS: A total of 2833 participants met inclusion criteria. The EQ-5D-5L index value, GAD-7, and SQS all improved at each follow-up (p < 0.001). There was no difference in EQ-5D-5L index values between former or current illicit cannabis consumers and naïve patients (p > 0.050). Adverse events were reported by 474 (16.73%) participants. CONCLUSIONS: This study suggests that CBMPs are associated with an improvement in health-related quality of life in UK patients with chronic diseases. Treatment was tolerated well by most participants, but adverse events were more common in female and cannabis-naïve patients.

Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study.

INTRODUCTION: There is growing evidence on the efficacy of cannabis-based medicinal products (CBMPs) for chronic pain (CP). Due to the interaction between CP and anxiety, and the potential impact of CBMPs on both anxiety and CP, this article aimed to compare the outcomes of CP patients with and without co-morbid anxiety following CBMP treatment. METHODS: Participants were prospectively enrolled and categorized by baseline General Anxiety Disorder-7(GAD-7) scores, into 'no anxiety'(GAD-7 < 5) and 'anxiety'(GAD-7 ≥ 5) cohorts. Primary outcomes were changes in Brief Pain Inventory Short-Form, Short-form McGill Pain Questionnaire-2, Pain Visual Analogue Scale, Sleep Quality Scale (SQS), GAD-7 and EQ-5D-5L index values at 1, 3 and 6 months. RESULTS: 1254 patients (anxiety = 711; no anxiety = 543) met inclusion criteria. Significant improvements in all primary outcomes were observed at all timepoints (p < 0.050), except GAD-7 in the no anxiety group(p > 0.050). The anxiety cohort reported greater improvements in EQ-5D-5L index values, SQS and GAD-7(p < 0.050), but there were no consistent differences in pain outcomes. CONCLUSION: A potential association between CBMPs and improvements in pain and health-related quality of life (HRQoL) in CP patients was identified. Those with co-morbid anxiety reported greater improvements in HRQoL.

An Updated Analysis of Clinical Outcome Measures Across Patients From the UK Medical Cannabis Registry.

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p<0.050. Results: Three hundred twelve patients were included in the final analysis, with a mean age of 44.8. The most common primary diagnoses were chronic pain of undefined etiology (n=102, 32.7%), neuropathic pain (n=43, 13.8%), and fibromyalgia (n=31, 9.9%). Before enrolment, 112 (35.9%) patients consumed cannabis daily. The median cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol doses prescribed at baseline were 20.0 mg (0.0-510.0 mg) and 3.0 mg (0.0-660.0 mg), respectively. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index, EQ-5D Visual Analog Scale and SQS scores at 1, 3, and 6 months (p<0.050). There were 94 (30.1%) reported adverse events, of which nausea (n=12, 3.8%), dry mouth (n=10, 3.2%), dizziness (n=7, 2.2%), and somnolence (n=7, 2.2%) were the most common. Conclusion: This study demonstrated CBMP treatment to be associated with a relatively low incidence of severe adverse events in the medium-term. Positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL outcomes. Randomized controlled trials are still awaited to assess causation; however, real-world evidence can help inform current clinical practice, future trials, and is an important component of pharmacovigilance.

Familial hemicrania continua.

There are now three known causative genes for familial hemiplegic migraine and increasing evidence to support a genetic predisposition to the more common types of migraine with and without aura, and for cluster headache. We present the first reported case of familial hemicrania continua. A mother and daughter developed hemicrania continua at the same time of life. Both showed an absolute response to indometacin and at similar doses. Both also suffered from migraine with aura. We discuss the increasing support for a genetic predisposition to dysfunction of the pain system within the brain manifesting as primary headache.

Fremanezumab autoinjector pen for the prevention of migraine.

Ajovy (fremanezumab, Teva Pharmaceuticals, Israel) is a fully humanized monoclonal antibody that selectively binds both isoforms of the calcitonin gene-related peptide. Calcitonin gene-related peptide is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events in migraine. It is indicated for prophylaxis of migraine in adults who have at least four migraine days per month, and can be administered as a subcutaneous injection using an autoinjector device, with two dosing options: 225 mg once a month or 675 mg quarterly. In this article, I present data from Phase III clinical trials of fremanezumab in episodic and chronic migraine, in which fremanezumab demonstrated efficacy and had a favorable tolerability profile, with no serious treatment-related adverse events.

An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients.

AIM: Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety. METHODS: A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3 months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050. RESULTS: There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n = 48; 37.2%). The median initial cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol daily dose was 20.0 mg (Range: 0.0-768.0 mg) and 3.9 mg (Range: 0.0-660.0 mg), respectively. Statistically significant improvements in health-related quality of life were demonstrated at 1 and 3 months in GAD-7, SQS, EQ-5D-5L pain and discomfort subscale, EQ-5D-5L anxiety and depression subscale, EQ-VAS and EQ-5D-5L index values(P < .050). There were 31 (24.03%) total reported adverse events. CONCLUSION: This study suggests that CBMP therapy may be associated with an improvement in health-related quality-of-life outcomes as self-reported by patients. CBMPs are also demonstrated to be relatively safe in the short to medium-term. These findings must be treated with caution given the limited scope of this initial analysis, with no placebo or an active comparator, with further research required.

Chronic daily headache.

Headache is a relatively neglected neurological disorder. Indeed, many neurologists find outpatient headache management--particularly of chronic daily headache--one of the least engaging parts of their job. The neglect of headache as a research problem has been reversed by the relatively recent emergence of strong programmes in centres such as Copenhagen, London, Philadelphia, New York, Liege and Leiden. Partly as a result of this, the pejorative attitude to headache as a clinical problem is less than it was, but many neurologists are still bemused by the intrusion of headache, both at a local level when headache patients occupy scarce specialist beds, and at a global level where the World Health Organization ranks migraine in the top 20 causes of global disability. This article reviews one of the commonest headache syndromes encountered by neurologists--chronic daily headache.

The diagnosis and treatment of chronic migraine.

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine.