Onabotulinumtoxin Type A reconstitution with preserved versus preservative-free saline in chronic migraine (B-RECON). A randomised, double-blind trial.

INTRODUCTION: Onabotulinumtoxin type A (BoNTA) is manufactured as powder that requires reconstitution with normal saline prior to injection. Previous literature has suggested that preserved saline (PS) exerts a local anaesthetic effect, and reduces the procedure discomfort when used in reconstitution in lieu of preservative-free saline (PFS). However, this was mainly studied in the aesthetics indications of BoNTA, and never in its use for the treatment of chronic migraine. The distinction is important as chronic migraine population suffers high incidence of scalp allodynia which makes it more prone to injection site pain. In addition, the pain of the procedure itself may be related to the spike of migraine frequency in the immediate postprocedural period which can occur in up to 5% of patients receiving the treatment. Our trial aimed to study the difference in procedural pain scale, and postprocedural headache rating with the use of PS vs PFS in constitution of BoNTA when used as a treatment for chronic migraine. METHODS: 68 subjects were consecutively enrolled in an outpatient setting at a large tertiary headache centre over a period of 6 months. Subjects were randomised into PS or PFS group. BoNTA was administered as per standard protocol in both groups. Injection site pain scores and frequency of headache days in the immediate following week were recorded. Wilcoxon rank sum tests were used to compare differences in between groups using SPSS software. RESULTS: Analysis (SAS V 9.4) revealed that those receiving [PF] had significantly higher procedure pain scores than those receiving [P] (5.3 vs 3.2, respectively). There was no difference in the headache or migraine frequency in the immediate postprocedural period. CONCLUSION: This study supports the use of PS (bacteriostatic) over PFS for reconstitution of BoNTA in chronic migraine as it reduces the discomfort of the injection sites.

The use, misuse and abuse of paraneoplastic panels in neurological disorders. A retrospective study.

OBJECTIVES: The field of paraneoplastic neurological syndromes PNS has grown exponentially with the increased identification of associated antibodies. Testing for these antibodies is commonly done in "panels" to increase sensitivity, and these panels have become a routine test on CSF samples obtained for a variety of clinical indications. Excessive testing has raised concerns about the correct utilization of these panels. Our study investigates the appropriateness of use of paraneoplastic panel in an academic, tertiary-care medical center. PATIENTS AND METHODS: We retrospectively reviewed charts of all patients who had autoimmune paraneoplastic panel testing in one year period. We collected date on demographics, clinical presentations and ancillary testings on all reviewed charts. Then, we devised an algorithm based on available data to define cases where testing had been unnecessary or likely unnecessary. RESULTS: We collected 60 cases that had undergone autoimmune paraneoplastic testing serum and/or CSF. Testing was unnecessary in 10 cases (16%), in which presentations had a definitive confirmatory tests. Testing was unlikely necessary in 11 cases (18%), in which all ancillary testing was normal in 6 cases, and presentation was not compatible with any known syndrome in 5 cases. Collectively, paraneoplastic panel testing was of extremely low yield on more than one third of the cases where where w testing was done. CONCLUSION: Our results adds to the growing concerns about the utilization of paraneoplastic panels, and the urgent need for enhanced screening and establishing a framework that can guide neurologists on when testing can have a sufficient yield to warrant it. Such framework should be built using diagnostic algorithms based on risk, clinical manifestations, characterization of autoantibodies and their associations.

OnabotulinumtoxinA wear-off in chronic migraine, observational cohort study.

INTRODUCTION: The current standard-of-care protocol for OnabotulinumtoxinA (BoNTA) injections consists of fixed-site injections every 12 weeks. This pattern is based on clinical practice and extrapolated from BoNTA injections for other, non-migraine-related indications. It is unclear if this protocol is optimal for chronic migraine. In clinical practice, migraine patients frequently describe a period of increased headache frequency and intensity in the few weeks preceding their next injections. In order to evaluate the duration of the clinical effect of BoNTA injections in chronic migraine, we studied the variation in headache frequency on a weekly basis during the 12-week period following treatment in a cohort of migraine patients. METHOD: 38 consecutive subjects were enrolled from an outpatient headache clinic, and asked to keep daily headache journals. 24 completed headache journals were analyzed. Headache frequency, duration and severity, as well as intake of symptomatic headache medications were recorded and compared among the different weeks. RESULTS: The time-response plot following BoNTA injection was roughly U-shaped, with 3 distinct phases: an induction phase, a maximum efficacy phase, and a wear-off phase. The time-response plot revealed that the wear-off commenced around the eighth week post injection. The mean difference in the number of headache days per week between the first and the eighth week was 1.8 (95% CI [0.670-2.830], p = 0.003). CONCLUSION: The effect of BoNTA injections on chronic migraines was not uniform throughout a 12-week period. A window of vulnerability to migraine attacks exist in the beginning and end of each cycle.

Perfusion Imaging in Autoimmune Encephalitis.

Encephalitis is characterized by inflammation of brain tissue and has various infectious and noninfectious causes. CSF analysis and MRI usually reveal inflammatory changes although sometimes brain imaging may be normal. Autoimmune encephalitis is caused by antibodies against neuronal synaptic receptors, surface proteins, or intracellular proteins. In this case report, we present a 65-year-old female who presented with a fall and altered mental status. Workup for infectious etiologies was negative and MRI of the brain displayed focal restricted diffusion with corresponding T2-FLAIR hyperintensity involving gray matter structures, making the diagnosis unclear. CT perfusion of the brain demonstrated increased cerebral blood volume and cerebral blood flow in the left parietooccipital gray matter, with corresponding normal mean transit time. Following treatment failure with acyclovir, antibiotics, and steroids, the patient was found to be positive for GAD65 antibodies and diagnosed with autoimmune encephalitis. Symptoms markedly improved with plasmapheresis. Autoimmune encephalitis rarely causes restricted diffusion and this is the first case report to describe corresponding hyperperfusion on CT perfusion study.

Extensive intracranial arterial stenoses in conjunction with the use of tyrosine kinase inhibitor Nilotinib.

New-generation tyrosine kinase inhibitors (TKI) are promising agents for the treatment of chronic myeloid leukemia (CML), but the linkage to vascular diseases warrants a special attention from treating physicians, as it may carry major morbidity and mortality.