Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are currently in clinical use. While considered safe and effective, their use has been rarely complicated by the development of antibodies that reduce or negate their therapeutic effect. The presence of antibodies has been attributed to shorter dosing intervals (and booster injections), higher doses per injection cycle, and higher amounts of antigenic protein. Other factors contributing to the immunogenicity of BoNT include properties of each serotype, such as formulation, manufacturing, and storage of the toxin. Some newer formulations with purified core neurotoxin devoid of accessory proteins may have lower overall immunogenicity. Several assays are available for the detection of antibodies, including both structural assays such as ELISA and mouse-based bioassays, but there is no consistent correlation between these antibodies and clinical response. Prevention and treatment of antibody-associated non-responsiveness is challenging and primarily involves the use of less immunogenic formulations of BoNT, waiting for the spontaneous disappearance of the neutralizing antibody, and switching to an immunologically alternate type of BoNT.

COG1410 administered at a dose of 2 mg/kg within 2 h after injury improves functional recovery in a murine model of ICH.

Background: Patients with essential tremor were initially considered to have isolated tremor, but additional motor and non-motor features have been increasingly recognized. The term "essential tremor plus" was adopted by the Task Force on Tremor of the International Parkinson and Movement Disorder Society to describe essential tremor patients with additional neurologic signs.Objectives: To characterize essential tremor patients and their phenotypes in a movement disorders clinic population in the context of the new tremor classification.Methods: Demographic, clinical, historical, treatment, and diagnostic data were retrospectively collected on 300 patients diagnosed by movement disorder experts with essential tremor. Patients were classified as having essential tremor, essential tremor plus, or essential tremor-Parkinson's disease combination, and features between these groups were compared. Results:Of the 300 patients, 20.7% were classified as isolated essential tremor, 53.3% as essential tremor plus, and 26.0% as essential tremor-Parkinson's disease. There was no significant difference in the duration of tremor symptoms. Essential tremor plus patients were more likely to have dystonia, tandem gait abnormalities, head tremor and greater tremor severity. Essential tremor-Parkinson's disease patients were more likely to have RBD symptoms. There was no significant difference in cognitive impairment between essential tremor plus and essential tremor-Parkinson's disease patients.Conclusions: Additional motor and non-motor features, including parkinsonism, are common in patients with essential tremor. Further studies are needed to clarify essential tremor phenotypes and to provide insights into possible subtypes.Highlights: 300 patients with essential tremor from a movement disorders clinic were re-classified based on the Movement Disorder Society Consensus Statement on the Classification of Tremors. Additional motor and non-motor features, including parkinsonism, were common, and only 20.7% of patients remained classified as isolated essential tremor.

Emerging evidence suggests sex and apolipoprotein E (APOE) genotype separately modify outcomes after intracerebral hemorrhage (ICH). We test the hypothesis that an interaction exists between sex and APOE polymorphism in modifying outcomes after ICH and is altered by administration of exogenous apoE-mimetic peptide. To define the effects of sex and APOE polymorphism in ICH, we created collagenase-induced ICH in male and female APOETR mice (targeted replacement mice homozygous for APOE3 or APOE4 alleles; n=12/group) and assessed performance on Rotarod (RR) and Morris water maze (MWM). To evaluate hematoma formation, we used hematoxylin and eosin staining at 24 h after injury (n=8/group). Using separate cohorts (n=12/group), apoE-mimetic peptide (COG1410 at 2 mg/kg) was administered after ICH, and mice were assessed by RR and MWM. Female mice outperformed male mice via RR and MWM by over 190% improvement through 7 days (RR) and 32 days (MWM) of testing after ICH (p<0.01). Female APOE3TR mice demonstrated improved function compared with all other groups (p<0.05) without any difference in hematoma volume at 24 h after injury in any group. Administration of a therapeutic apoE-mimetic peptide improved RR latencies through 7 days after ICH in male and female APOE4TR mice and MWM latencies over days 28–32 after ICH in male APOE4TR mice (p<0.05). Sex and APOE polymorphism influence functional outcomes in our murine model of ICH. Moreover, administration of exogenous apoE-mimetic peptide after injury differentially modifies the interaction between sex and APOE polymorphism.

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Objective: Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features.Methods: This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region.Results: For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34–40%) and depression (21–24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety.Conclusions: This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.

We appreciate the commentary on our article by Foster and Beard, both employees of Ipsen [...]

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