Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2.

PURPOSE: In the PROMISE-1 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-1) and PROMISE-2 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2) clinical trials, eptinezumab 100 mg and 300 mg met the primary efficacy end point, significantly reducing mean monthly migraine days across weeks 1 to 12. Clinical efficacy was also shown across key secondary end points. However, to determine if clinical efficacy varies across subgroups, it is necessary to determine efficacy in patients with different sociodemographic features and headache characteristics. These post hoc analyses of patients in PROMISE-1 and PROMISE-2 evaluated the impact of intrinsic factors on the efficacy and safety of eptinezumab in subgroups defined according to baseline demographic and migraine disease characteristics. METHODS: PROMISE-1 and PROMISE-2 were Phase III, parallel-group, double-blind, randomized, placebo-controlled trials of repeat quarterly intravenous infusions of eptinezumab or placebo in adults with episodic (PROMISE-1) or chronic (PROMISE-2) migraine. FINDINGS: Demographic and baseline characteristics were similar across treatment groups in both the PROMISE-1 and the PROMISE-2 studies. Analyses did not show a clear pattern of baseline demographic characteristics driving treatment effects except for the obesity subgroups. For the ≥50% migraine responder rate in the obese class I (body mass index 30.0-35.0 kg/m2) subgroup, although separation from placebo was not as large (<10% separation compared with ≥10% separation across most baseline demographic factors), both doses showed improved ≥50% migraine responder rate compared with placebo, with slightly better results in patients receiving eptinezumab 300 mg. IMPLICATIONS: Eptinezumab treatment showed consistent clinically relevant reductions from baseline in mean monthly migraine days compared with placebo based on ≥50% migraine responder rate across clinically important intrinsic subgroups of adults with episodic or chronic migraine. CLINICALTRIALS: gov identifiers: NCT02559895 (PROMISE-1) and NCT02974153 (PROMISE-2).

Validity and reliability of the Georgian-language brief international cognitive assessment for multiple sclerosis (BICAMS).

BACKGROUND: Cognitive impairment is one of the common features of multiple sclerosis (MS). Despite high prevalence, cognitive decline is often overlooked by neurologists. The Brief International Cognitive Assessment for MS (BICAMS) was therefore introduced by the international expert committee as a brief and effective tool for the assessment and monitoring of cognitive functions in patients with MS. The validity and reliability of BICAMS have been demonstrated in many countries. Our aim was to validate the BICAMS in Georgian patients with MS. METHODS: A total of 68 patients with MS and 68 matched controls were assessed by the Georgian-language BICAMS. All healthy controls and seven patients were re-evaluated with identical tests to assess retest reliability. RESULTS: In comparison to healthy controls, patients with MS performed significantly worse on all tests in the assessment battery. Test-retest reliability measures were good for all tests. The prevalence of cognitive impairment in patients with MS was 43%. CONCLUSION: The Georgian-language BICAMS is a reliable and valid battery for the assessment of cognitive function in patients with MS.

Screening of Cognitive Impairment in Patients with Multiple Sclerosis: A Cross-Sectional Study in Georgia.

Cognitive impairment (CI) is a common symptom of multiple sclerosis (MS), with a significant negative impact on the occupational and social functioning of patients. This study aimed to estimate the prevalence and characteristics of CI among MS patients in Georgia. Sixty-eight patients with MS attending a neurology outpatient clinic in Tbilisi, Georgia, were enrolled in the study. Cognitive status was evaluated using two screening tools: the Brief International Cognitive Assessment for MS and the Montreal Cognitive Assessment. The overall prevalence of CI in our MS patients was 47%. We found negative associations between cognitive test results and patients' age, disability status, and depression. Lower education, higher scores on the Expanded Disability Status Scale, and the progressive course of MS were the main predictors of CI in the logistic regression analysis. This is the first study in Georgia to evaluate CI in patients with MS. The prevalence of CI in our study was comparable with those reported in other countries; however, we found greater impairment of the executive system compared to other cognitive domains. In our study, patients who were on continuous DMT showed significantly better performance on the cognitive tests used, indicating possible favorable effect of immunomodulatory drugs on cognition.

Acute Disseminated Encephalomyelitis Following Chemoradiotherapy in an Adult Patient With Nasopharyngeal Cancer.

Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disorder predominantly affecting children. It typically follows a viral illness or vaccination. We present a case of a 34-year-old white male treated with chemo-radiotherapy for nasopharyngeal cancer who developed ADEM. Prompt initiation of intravenous steroids led to the resolution of symptoms and normalization of the brain imaging. We hypothesized that direct brain tissue damage by chemotherapy and radiation therapy, combined possibly with a viral infection, triggered an immune inflammatory response and subsequent demyelination.

Eptinezumab for the Prevention of Episodic Migraine: Sustained Effect Through 1 Year of Treatment in the PROMISE-1 Study.

PURPOSE: The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy 1 (PROMISE-1) study was a phase III, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, tolerability, and pharmacokinetic properties of repeat intravenous (IV) doses of the calcitonin gene-related peptide‒targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with episodic migraine. Here we present the results of PROMISE-1 through 1 year of treatment (up to 4 doses). METHODS: Patients received up to 4 IV administrations of eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks. Patients recorded migraine and headache in an electronic diary daily. Additional assessments, including the patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 56-week study period. FINDINGS: A total of 888 adults (mean age, 39.8 years; 84.3% female; 83.8% white) received treatment: eptinezumab 30 mg, n = 219; eptinezumab 100 mg, n = 223; eptinezumab 300 mg, n = 224; and placebo, n = 222. During the primary 12-week study evaluation period, single doses of eptinezumab 100 mg and 300 mg led to significant reductions in mean monthly migraine-days versus placebo, beginning as early as the first day after the initial dose. The reduction in mean monthly migraine-days was maintained throughout the study (100 mg, -3.9, -4.5, -4.7, and -4.5 days; 300 mg, -4.3, -4.8, -5.1, and -5.3 days; and placebo, -3.2, -3.8, -4.0, and -4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). Overall, the number of patients with a ≥50% or ≥75% reduction in migraine for each 12-week interval during the entire study was consistently numerically higher in the eptinezumab groups than in the placebo group. The proportions of patients with ≥50% reduction in migraine were similar across the eptinezumab groups. Eptinezumab was well tolerated throughout the study. Adverse events were similar across dosing periods, and there were no serious tolerability signals identified with continued dosing. IMPLICATIONS: IV eptinezumab administered every 12 weeks for up to 4 doses was associated with early and sustained migraine-preventive effects and a favorable safety profile in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895.

Mild Cognitive Impairment in Republic of Georgia.

Objective: The goal of this study was to estimate the prevalence of mild cognitive impairment (MCI) in Georgia. Method: A population-based study was conducted using Georgian version of the Montreal Cognitive Assessment (MoCA) and its cognitive domain index score. Results: Of the initial cohort of 1,000 subjects, 851 met inclusion criteria. The prevalence of MCI was 13.3%, and it was associated with age >65 years (odds ratio [OR] = 4.51, 95% confidence interval [CI] = [3.00, 6.75]), urban residence (OR = 0.53, 95% CI = [0.33, 0.88]), lower education (OR = 3.99, 95% CI = [2.66, 5.93]), and hypertension (OR = 2.51, 95% CI = [1.68, 3.76]), while amnestic MCI was documented in 9.3%, with higher risk in older subjects (OR = 2.69, 95% CI = [1.66, 4.20]), and diabetics (OR = 2.69, 95% CI = [1.25, 5.98]). Conclusion: In this first population-based study of MCI in Georgia, prevalence was comparable with those reported from the United States and Europe. Observed association of MCI with cardiovascular risk factors has important clinical implication for dementia prevention in Georgia.

Use of the universal pain assessment tool for evaluating pain associated with TMD in youngsters with an intellectual disability

BACKGROUND: The Universal Pain Assessment Tool (UPAT) was used to assess the level of pain in people with limited communication skills. The UPAT enables clinicians to consult a specialized pain management team more often and lead to earlier interventions. The purpose of this study was to determine, whether the UPAT could be used as an extra tool to collect data on functional TMJ pain and to assess orofacial pain levels related to temporomandibular disorder(s) (TMD) in people with intellectual disabilities (ID). MATERIAL AND METHODS: Non-down syndrome ID Athletes were screened during the Special Olympics European games in 2014. The clinical scores of possible functional jaw pain were collected using the UPAT, to indicate pain severity on a visual scale during different jaw movements (opening, closing and lateral). RESULTS: Two hundred and four youngsters were screened by calibrated dentists. The majority (65%) of participants were male (133 male and 71 female athletes); age distribution ranged from 15 to 23 years (mean 19.25 ± 2.53). The results of the UPAT have shown the existence of functional TMJ pain in 32% (n=65) of the athletes without significant prevalence (P > 0.05) in this survey group. CONCLUSIONS: According to the results of the present study, the UPAT demonstrated that it could be a useful tool to detect the existence of functional jaw pain possibly associated with TMD and also a valid instrument to score pain intensity associated with TMD in people with ID

Validity of the Georgian Montreal Cognitive Assessment for the Screening of Mild Cognitive Impairment and Dementia.

Montreal Cognitive Assessment (MoCA) test has been shown to be a reliable tool to detect mild cognitive impairment (MCI), however, no Georgian language version exists. The goal of this study is to determine the validity, reliability, and accuracy of Georgian version of MoCA in the evaluation of amnestic MCI (aMCI) and Alzheimer's disease (AD). Montreal Cognitive Assessment was translated into Georgian language and was administered to healthy participants (HP) and patients with aMCI and AD. We studied 46 HS, 20 patients with aMCI, and 20 patients with AD. There was significant difference in MoCA scores between HP, patients with aMCI, and patients with AD ( P = 0.04). The area under the receiver operating characteristic curve for the aMCI and AD groups by MoCA was 0.88 and 0.95, respectively, compared to 0.43 and 0.67 by Mini-Mental State Examination (MMSE). The Georgian version of MoCA is a valid, reliable, and sensitive screening tool to detect aMCI and AD in Georgian-speaking population and is superior to MMSE.

Eye movements in ephedrone-induced parkinsonism.

Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system.

A distinct variant of mixed dysarthria reflects parkinsonism and dystonia due to ephedrone abuse.

A distinctive alteration of speech has been reported in patients suffering from ephedrone-induced parkinsonism. However, an objective assessment of dysarthria has not been performed in ephedrone users. We studied 28 young Caucasian men from Georgia with a previous history of ephedrone abuse and compared them to 25 age-matched healthy controls. Speech examination, brain MRI, and NNIPPS-Parkinson plus scale were performed in all patients. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analyses of 15 speech dimensions. We revealed a distinct variant of mixed dysarthria with a combination of hyperkinetic and hypokinetic components representing the altered motor programming of dystonia and bradykinesia in ephedrone-induced parkinsonism. According to acoustic analyses, all patients presented at least one affected speech dimension, whereas dysarthria was moderate in 43% and severe in 36% of patients. Further findings indicated relationships between motor subscores of dystonia and bradykinesia and speech components of loudness (r = -0.54, p < 0.01), articulation (r = 0.40, p < 0.05), and timing (r = -0.53, p < 0.01). In ephedrone-induced parkinsonism a prominent mixed hyperkinetic-hypokinetic dysarthria occurs that appears related to marked dystonia and bradykinesia and probably reflects manganese induced toxic and neurodegenerative damage to the globus pallidus internus and substantia nigra.

Validation of a Georgian language headache questionnaire in a population-based sample.

In a pilot phase of a survey of the prevalence of primary headache disorders in the Republic of Georgia, we validated a Georgian language questionnaire for migraine (MIG), tension-type headache (TTH), MIG+TTH and trigeminal autonomic cephalalgias (TAC). A population-based sample of 186 people with headache completed the questionnaire and were blindly examined by one of two headache experts. The questionnaire diagnoses were: MIG 49, TTH 76, MIG+TTH 45 and TAC 16. The physicians' diagnoses were: MIG 59, TTH 77, MIG+TTH 34, TAC 2 and "symptomatic headache" in 14 subjects. Sensitivity and specificity for MIG were 0.75 and 0.96, for TTH 0.79 and 0.86, and for MIG+TTH 0.61 and 0.84 respectively. Of 16 TAC diagnoses, the physicians confirmed cluster headache in two patients only. The questionnaire can be utilised to investigate the prevalence of MIG and of TTH. It offers preliminary screening only for TAC, which should be confirmed during a face to face examination.