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[P01.085] Evaluation of Cerebral Hemodynamics of Patients with Chronic Migraine: Effects of the Botulinum Neurotoxin-A

Hakan Akgun, Ankara, Turkey, Serdar Tasdemir, Ankara, Turkey, Mehmet Yucel, Istanbul, Turkey, Oguzhan Oz, Ankara, Turkey, Umit Ulas, Ankara, Turkey, Seref Demirkaya, Ankara, Turkey, Yasar Kutukcu, Ankara, Turkey

OBJECTIVE: Migraine is a neurovascular disorder. Change in the diameter of intracranial arteries is thought to be an important underlying mechanism in migraine pathophysiology. Transcranial-Doppler-Ultrasound (TCD) is a non-invasive method to evaluate intracranial vascular system. Recent studies showed that botulinum neurotoxin-A (BoNTA) is an effective treatment choice in migraine headache. BACKGROUND: We aimed to evaluate the changes in middle cerebral artery (MCA) and posterior cerebral artery (PCA) in terms of Mean Blood Flow Velocity, Breath-Holding-Index (BHI) and pulsatility index (PI) in patients with chronic migraiene before and after treatment with BoNTA by using TCD. DESIGN/METHODS: The study included 25 patients with chronic migraine. 12 patients were treated with high-dose (100 IU) BoNTA and 13 patients were treated with low-dose BoNTA (50 IU). BoNT was injected to facial, scalp and neck muscles. Mean blood flow velocity, BHI and PI were measured before and 7 days after BoNTA injection in MCA and PCA bilaterally in both groups. We compared the pre-treatment and post-treatment values. We also evaluated the Visual Analogue Scale (VAS) scores in both groups before and after-treatment. RESULTS: Pulsatility index was significantly decreased in MCA (before treatment PI=0,74±0,13, after treatment PI=0,69±0,10) (p=0.024) and insignificantly changed in PCA after treatment in high-dose group (p>0.05). Differences in Mean blood flow velocity and BHI were insignificant in both groups in both arteries (p>0.05). VAS scores significantly decreased after treatment in both groups (p<0.001). CONCLUSIONS: The PI is a well known indicator of peripheral vascular resistance. Our results suggest that BoNTA treatment may be effective by reducing the resistance in intracranial vascular beds in patients with chronic-migraine.
Category - Headache: Therapeutics

[P01.182] Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis: Patient-Reported Outcomes (PRO)

Moogeh Baharnoori, Toronto, ON, Canada, Stephen C. Wong, Toronto, Canada, Marika Hohol, Toronto, ON, Canada, Paul O'Connor, Toronto, ON, Canada

OBJECTIVE: To assess changes in multiple sclerosis (MS) associated symptoms and disability scores (EDSS) in patients with MS after endovascular treatment (ET). BACKGROUND: The chronic cerebrospinal venous insufficiency (CCSVI) hypothesis has been proposed as the causal factor for MS. Contradictory data on the association between CCSVI and MS have been reported to date. CCSVI was defined as impaired extra cranial cerebrospinal venous drainage which leads to the accumulation of cerebral iron deposits causing inflammation and degeneration. DESIGN/METHODS: 82 eligible patients completed a questionnaire regarding changes in their MS symptoms after ET including fatigue, sensory deficits, impairments in mobility, coordination, bladder control and cognition. First, we examined symptom changes within 2 weeks after treatment compared to before. For longitudinal assessment, we divided patients to 3 groups; patients who had ET 1) within past 6 month 2) 6-12 months or 3) more than 12 months. Changes at the time of interview were compared to those before the ET. Their EDSS score was measured before and after ET and analyzed using student t test. RESULTS: Within 2 weeks after treatment, 70% (56/79) reported decreased fatigue. About two-thirds reported improvement in cognition (38/65), mobility (51/79) and perceived warming in their limb temperature (40/63). Half of patients reported improvement in bladder control (34/73), coordination (37/73) and sensory deficits (28/61). Longitudinal assessment of symptoms revealed that initial reported improvement in most symptoms greatly diminished over time. Furthermore, we did not find any significant difference between EDSS scores before and after the ET (P=0.828). CONCLUSIONS: Our findings indicate that ET procedures for CCSVI are associated with subjective reports of improvement of various symptoms by many patients without any corresponding objective change in neurological evaluations as measured by neurologist-derived EDSS scores. These uncontrolled and unblinded observations do not provide any credible evidence of a true benefit from ET for MS.

For longitudinal assessment, we divided patients to 3 groups; patients who had ET 1) within past 6 month 2) 6-12 months or 3) more than 12 months.

[P05.177] An Assessment of Chronic Cerebrospinal Venous Insufficiency in MS

Robert Fox, Cleveland, OH, Leasa Baus, Cleveland, OH, Claudiu Diaconu, Cleveland, OH, Alia Grattan, Cleveland, OH, Diane Ivancic, Cleveland, OH, Soo-Hyun Kim, Cleveland, OH, Jar-Chi Lee, Cleveland, OH, Mei Lu, Cleveland, OH, Larry Raber, Cleveland, OH, Sneha Ramesh, Cleveland, OH, Alexander Rae-Grant, Cleveland, OH

OBJECTIVE: To conduct an independent assessment of chronic cerebrospinal venous insufficiency (CCSVI) in MS. BACKGROUND: CCSVI is a hypothesis of MS pathogenesis related to venous outflow from the head, with conflicting results from different studies. Recent studies have found a very low prevalence of CCSVI, suggesting that those investigators were performing ultrasound assessments differently than the original reports. DESIGN/METHODS: After obtaining formal training in CCSVI ultrasound techniques, we performed ultrasound assessments on a group of 61 MS subjects (4 CIS, 28 RRMS, 19 SPMS, 10 PPMS; 42 females) and 20 non-MS controls (15 healthy and 5 other neurological diseases; 10 female). Ultrasonographers were blinded to diagnosis, and separate research staff positioned subjects prior to ultrasonographer arrival. Assessments were performed using a Biosound MyLab25, equipped with Quality Doppler Profiles (QDP) technology, and traditional transcranial Doppler. Two published interpretations of CCSVI Criteria were utilized: Narrow Criteria did not include either B-mode intraluminal abnormalities or QDP technology for deep cerebral vein reflux, while Broad Criteria included both of these. RESULTS: Using either Narrow Criteria or Broad Criteria, there were no significant differences between MS subjects and controls (p>0.5 for both comparisons). In both groups, there was a doubling of the proportion of subjects meeting CCSVI criteria when using the Broad Criteria. CONCLUSIONS: Using trained and blinded ultrasonographers and QDP technology, we observed no difference in the proportion of MS subjects meeting CCSVI criteria compared to non-MS controls. Different interpretations of CCSVI criteria altered the proportions of subjects meeting CCSVI criteria, highlighting the importance of criteria interpretations when comparing the prevalence of CCSVI between studies. These observations do not support a significantly increased prevalence of CCSVI in MS and suggest against a pathogenic role of CCSVI in MS. Supported by: Research grant from National MS Society (RC 1004-A-5).

[P05.183] Chronic Cerebrospinal Venous Insufficiency and Multiple Sclerosis: Changes in Treatment Patterns and Opinions in a Province-Wide Study

Luanne Metz, Calgary, AB, Canada, Ruth-Ann Marrie, Winnipeg, MB, Canada, Katayoun Alikhani, Calgary, AB, Canada, Gregg Blevins, Edmonton, AB, Canada, Jacqueline Bakker, Red Deer, AB, Canada, Larry Svenson, Edmonton, AB, Canada, Nathalie Jette, Calgary, AB, Canada, Oksana Suchowersky, Edmonton, AB, Canada, Mary Louise Myles, Edmonton, AB, Canada, Winona Wall, Calgary, AB, Canada, James Newsome, Calgary, AB, Canada, Jamie Greenfield, Calgary, AB, Canada, Marcus Koch, Calgary, AB, Canada, Scott Patten, Calgary, AB, Canada, Scott Kraft, Calgary, AB, Canada, Derek Emery, Edmonton, AB, Canada, Mayank Goyal, Calgary, AB, Canada

OBJECTIVE: We aimed to describe the population of Multiple Sclerosis (MS) patients reporting chronic cerebrospinal venous insufficiency (CCSVI) treatment and to describe the change in treatment patterns and opinions over time. BACKGROUND: The CCSVI hypothesis has been of great interest to MS patients. Many Albertans have travelled out-of-country for venous angioplasty. DESIGN/METHODS: Initiated in July 2011, The Alberta Multiple Sclerosis Initiative is a longitudinal observational study that uses online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following CCSVI treatment. All Albertans with MS have been encouraged to participate, irrespective of treatment status. Enrollment is ongoing. RESULTS: This analysis included 733 participants. Mean (SD) age was 47.9 (11.2) years, 76.5% were female, and 63.8% had relapsing remitting MS; 152 participants (20.7%; 95% CI: 17.9-23.9%) reported having CCSVI treatment, beginning in March 2010. Participants were more likely to have undergone treatment in 2010 (66.4%; 95% CI: 58.3-73.9%, n=101) than in 2011 (30.9 %; 95% CI: 23.7-38.9%, n=47), even after controlling for the period of enrolment. Between January and June 2012 only four participants had CCSVI treatment (2.6%; 95% CI: 0.7-6.6%). Older age, male sex, a progressive course, and greater disability were more common in those who had CCSVI treatment. CONCLUSIONS: The number of participants reporting CCSVI treatment is declining. This may indicate that patients who wanted and could afford out-of-country treatment went soon after the CCSVI hypothesis was widely publicized. However, this may also reflect declining patient interest after they observed the outcomes in this earlier group of patients. The sociodemographic and clinical characteristics of participants who received CCSVI treatment will be compared to those who did not receive treatment. Factors that influenced participants' opinions for or against having CCSVI treatment will be compared over time. Supported by: Alberta Health.

Participants were more likely to have undergone treatment in 2010 (66.4%; 95% CI: 58.3-73.9%, n=101) than in 2011 (30.9 %; 95% CI: 23.7-38.9%, n=47), even after controlling for the period of enrolment. Between January and June 2012 only four participants had CCSVI treatment (2.6%; 95% CI: 0.7-6.6%). Older age, male sex, a progressive course, and greater disability were more common in those who had CCSVI treatment.

CONCLUSIONS: The number of participants reporting CCSVI treatment is declining. This may indicate that patients who wanted and could afford out-of-country treatment went soon after the CCSVI hypothesis was widely publicized. However, this may also reflect declining patient interest after they observed the outcomes in this earlier group of patients. The sociodemographic and clinical characteristics of participants who received CCSVI treatment will be compared to those who did not receive treatment. Factors that influenced participants' opinions for or against having CCSVI treatment will be compared over time. Supported by: Alberta Health.

It's incredibly discouraging to see these abstracts---but if researchers are not interested in understanding cerebral perfusion and how it effects aspects of MS that are not reflected by the EDSS scale (cog fog, heat intolerence, fatigue, spasms), then there really is no future for CCSVI studies by MS specialists.

[P04.034] Aerobic Exercise Increases Hippocampal Volume and Improves Memory in Persons with Multiple Sclerosis: Pilot Findings from a Randomized Controlled Trial

Victoria Leavitt, West Orange, NJ, Amanda Cohen, West Orange, Amanda Farag, West Orange, Christopher Cirnigliaro, West Orange, NJ, Nancy Chiaravalloti, West Orange, NJ, James F. Sumowski, West Orange, John DeLuca, West Orange

OBJECTIVE: Aerobic exercise improves memory and promotes hippocampal neurogenesis in non-human animals. Its efficacy has not been verified in a memory-impaired neurologic sample. Here, a randomized controlled trial of aerobic versus non-aerobic exercise was piloted in multiple sclerosis (MS) patients with memory impairment. BACKGROUND: MS leads to prominent hippocampal atrophy: as much as 10% reduction of hippocampal volume is seen in persons with relapsing-remitting MS (RRMS), even after only five years. Hippocampal atrophy is linked to memory deficits; indeed, more than 50% of MS patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for MS, either pharmacological or behavioral. DESIGN/METHODS: Pilot data were collected from two ambulatory, memory-impaired MS participants randomized to non-aerobic (stretching) and aerobic (stationery cycling) conditions. Baseline and follow-up measurements: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30 minute sessions 3 times per week for 3 months. RESULTS: Aerobic exercise resulted in a 16.5% increase in hippocampal volume and a 53.7% increase in memory, as well as a large increase in hippocampal resting-state functional connectivity. In contrast, non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal resting-state functional connectivity. Effects of aerobic exercise were specific to the hippocampus and memory, as there were no comparable changes in overall cerebral gray matter (2.4%) or in non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), nor were there any changes in non-memory cognitive functioning (mean change: 0.0%). CONCLUSIONS: This is the first evidence for aerobic exercise to increase hippocampal volume, hippocampal connectivity, and improve memory in MS. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for MS patients.
Category - Neural Repair/Rehabilitation: Clinical: Multiple Sclerosis

[S40.004] Non-Invasive Vagus Nerve Stimulation (nVNS) for Acute Treatment of Migraine: An Open-Label Pilot Study

Peter Goadsby, San Francisco, CA, Richard Lipton, Bronx, NY, Roger Cady, Springfield, MO, Alexander Mauskop, New York, NY, Brian Grosberg, Bronx, NY

OBJECTIVE: Assessment of a novel, non-invasive, portable VNS device for acute treatment of migraine. BACKGROUND: Despite many acute treatment options for migraine, substantial unmet need remains. VNS is promising, but relatively unexplored. DESIGN/METHODS: Participants with migraine with or without aura, as defined by the International Classification of Headache Disorders- second edition, were eligible for an open-label, single arm, multiple attack study. Participants acutely treated up to 4 migraine attacks with a portable VNS within 6 weeks. Treatment consisted of two, 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve. Subjects were asked to self-treat once pain became moderate or severe, or after 20 minutes of mild pain. RESULTS: Of 30 enrolled patients, (5M, 25F, average age 39), 26 eligibly treated 79 migraine headaches . At two hours, headache response rate (pain mild or absent at 2 hours) was 46/79 (58%), and 22/79 (28%) were pain free. Average initial pain level was a 1.84 (0-no pain, 1-mild, 2-moderate, 3-severe pain), and dropped 35%, to 1.20 (p<0.0001) by 2 hours . At two hours, 76 of 79 (96%) were improved or had not worsened over baseline. Of 26 patients 20 (77%) responded, i.e., reported mild or nor pain at 2 hours, for at least one treated headache. Among this subset of 20 patients 47/61 (77%) of their treated headaches responded. Treatment related adverse effects were limited to transient muscle or local tissue irritation, and two reports of light headedness, most of which resolved immediately after treatment, and all within two hours of treatment. CONCLUSIONS: These results suggest that nVNS may be an effective and well-tolerated acute treatment for migraine in a responsive subgroup. Randomized controlled trials are warranted. Supported by: ElectroCore, LLC.