Publications:

The Department of Neurology at Lahey Hospital & Medical Center supports and participates in various original research efforts.  These efforts include investigator-initiated drug or device trials, observational studies, questionnaire studies, outcome studies, case reports and retrospective reviews. The results of these original projects are often published in peer reviewed journals.

2013 Publications: 

McMillan HJ, Kang PB, Jones HR, Darras BT. "Childhood chronic inflammatory demyelinating polyradiculoneuropathy: Combined analysis of a large cohort and eleven published series". Neuromuscul Disord. 2013 Feb;23(2):103-11

• ABSTRACT: The clinical presentation, disease course, response to treatment, and long-term outcome of thirty childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients are presented representing the largest cohort reported to date. Most children (60%) presented with chronic (>8-weeks) symptom-onset while a smaller proportion showed sub-acute (4-8 weeks) or acute (''GBS-like''; <4 weeks) onset of disease. No gender predilection was observed. The majority of patients had a relapsing (70%) versus a monophasic (30%) temporal profile. Most received initial IVIG monotherapy; 80% showing a good response. Long-term follow-up (mean=3.8 years) was available for 23 patients; 45% were off all immunomodulatory medications, demonstrating no detectable (55%) or minimal (43%) clinical deficits. Our data were compared with 11 previously published childhood CIDP series providing a comprehensive review of 143 childhood CIDP cases. The combined initial or first-line treatment response across all studies was favorable for IVIG (79% patients) and corticosteroids (84% patients). Response to first-line plasma exchange was poor (only 14% patients improved) although it may offer some transient or partial benefit as an adjuvant or temporary therapy for selected patients. The combined long-term outcome of our cohort and the literature reveals a favorable prognosis for most patients. The combined modified Rankin scale decreased from 3.7 (at presentation) to 0.7 (at last follow-up). This review provides important data pertaining to clinical course, treatment response and long-term outcome of this relatively uncommon pediatric autoimmune disease. PMID: 23140945 

Karakis I, Jones HR, Gajjar AA, Baharozian DB, Srinivasan J. "Teaching NeuroImages: Gelsolin-related amyloidosis: A rare cause of progressive facial diparesis". Neurology. 2013 Feb 26;80(9):e94.

• ABSTRACT: A 71-year-old diabetic man of German-Polish heritage, with no relevant family history, presented with 4 years of slowly progressive bilateral facial weakness. Clinical examination demonstrated bilateral, asymmetric facial paresis and skin laxity (figure 1). Screening ophthalmologic examination for diabetic complications revealed bilateral corneal lattice dystrophy (figure 2). EMG showed bilateral facial neuropathies, carpal tunnel syndrome, and mild axonal polyneuropathy. Genetic testing for gelsolin amyloidosis identified heterozygous status for Gelsolin-Asn187 (G654A mutation). Familial gelsolin-related amyloidosis of Finnish type, also known as Meretoja syndrome, is a rare, autosomal dominant cause of progressive facial diparesis associated with cutis laxa and corneal lattice dystrophy.  PMID:23439710 

To see a listing of neurology publications by Lahey neurology staff in previous years, click below: 

2012 

2011 

2010 

Complete articles or abstracts may be available at http://www.ncbi.nlm.nih.gov/pubmed/  

Poster Presentations:

Physicians from the Department of Neurology also regularly present preliminary or final results of their original research in the format of poster presentations at peer reviewed neurological meetings often hosted by international professional associations or organizations, including the highly regarded annual meetings of the American Academy of Neurology and American Neurological Association.

Recent Poster Presentations:  

To preview recent posters, click on one of the poster titles below.  

March 2013:

The 65^th Annual Meeting of the American Academy of Neurology (AAN) 

• Sporadic Creutzfeldt-Jakob Presenting with Fixed Focal Dystonia  

October 2012: 

The 136th Meeting of the American Neurological Association (ANA) 

• Low Frequency DBS in PD Patients with Gait and Speech Problems 
• Chronic Parkinsonism Associated with Liver Cirrhosis 
• Anxiety in Benign Fasciculation Syndrome 
• Subacute Combined Degeneration of the Spinal Cord Due to Functional B12 Deficiency  
• A Severe Case of Recurrent Coccidioidal Meningitis Complicated by Hydrocephalus  

June 2012: 

The Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC)  

• Incidence of Silent Spinal Cord Lesions in Relapsing Remitting Multiple Sclerosis    
• Clinical Aspects of Multiple Sclerosis Patients with Normal Spinal Cord Imaging 
• T-cell Subtype in Multiple Sclerosis Patients Treated with Fingolimod 

The 26th Annual Meeting of the Associated Professional Sleep Societies (APSS) 

• A retrospective study on ordering subsequent CPAP titration studies in Mild Sleep Apnea with REM predominance 

The 16th International Congress of Parkinson's Disease and Movement Disorders 

• Parkin gene mutation with an autosomal dominant inheritance- a family case report 

April 2012: 

The 64th Annual Meeting of the American Academy of Neurology (AAN) 

• Predictors of Charcot-Marie-Tooth Disease in Patients with Pes Cavus Deformities  
• Effect of Prior Antiplatelet Therapy on Risk and Type of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis.  Shruti Sonni, MD, Adam Drobnis, MD, Claudia Fitzgerald, Kinan Hreib, MD and Matthew Tilem, MD  

The 50th Annual Meeting of the American Society of Neuroradiology (ASNR) & The Foundation of the ASNR Symposium   

• Ruptured Intrameatal Anterior Inferior Cerebellar Artery Aneurysm: Endovascular Management is a Viable Treatment Option.  Block Lee, S.Christoforidis, G., Hreib, K, and David, C 

February 2012:

• Clock Drawing in PD: What makes the clock drawing test tick?  Cunningham, H., Penney, D., Davis, R., Tanner, J. J., Nguyen, P. T., Schwab, N., Malaty, I., Okun, M. S., Bowers, D., Libon, D. J., Price, C. C.

 

Clinical Trial Results:

Clinical drug and device trials sponsored by pharamceutical and biotechnology companies are regularly conducted in the department of neurology at Lahey Hospital & Medical Center.  Once the results of these trials are finalized they are published in peer reviewed journals, and results may also be found on www.clinicaltrials.gov.

Recent Results:

Results of the NINDS and Mt. Sinai School of Medicine sponsored CombiRx clinical trial, “A Multicenter Double-Blind Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients with RRMS”, were published in the February 2013 journal of Annals of Neurology  (Lublin FD, Cofield SS, Cutter GR, Conwit R, Narayana PA, Nelson F, Salter AR, Gustafson T, Wolinsky JS; for the CombiRx Investigators. Randomized study combining interferon & glatiramer acetate in multiple sclerosis. Ann Neurol. 2013 Feb 19.) 

• Ann Camac, MD was the Lahey Hospital & Medical Center principal investigator and a total of 10 Lahey patients were enrolled into the trial.   
• ABSTRACT:  OBJECTIVE: A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS). METHODS: 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score and MRI metrics. RESULTS: Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The Combination was not better than either agent alone in lessening confirmed EDSS progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity free status (DAFS) compared to either single arm; driven by the MRI results. INTERPRETATION: Combining the two most commonly prescribed therapies for MS did not produce a significant clinical benefit over three years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address if the observed differences in MRI and DAFS findings predict later clinical differences. PMID:23424159
   

Results of the Allon Therapeutics, Inc. sponsored clinical trial, "A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy", were announced on December 18, 2012.   

• Julie Leegwater-Kim, MD, PhD was the Lahey Hospital & Medical Center principal investigator and a total of 2 Lahey patients were enrolled into this trial. summary of the results can be found on the Allon Therapeutics website: www.allontherapeutics.com 

Results of the Biogen Idec sponsored clinical trial, “A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study To Determine The Efficacy And Safety Of BG00012 In Subjects With Relapsing-Remitting Multiple Sclerosis”, were published in the September 2012 issue of the New England Journal of Medicine.  (Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1098-107.) 

• Ann Camac, MD was the Lahey Hospital & Medical Center principal investigator.  
• ABSTRACT: BACKGROUND: BG-12 (dimethyl fumarate) was shown to have antiinflammatory and cytoprotective properties in preclinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging (MRI) in a phase 2, placebo-controlled study involving patients with relapsing-remitting multiple sclerosis. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 3 study involving patients with relapsing-remitting multiple sclerosis. Patients were randomly assigned to receive oral BG-12 at a dose of 240 mg twice daily, BG-12 at a dose of 240 mg three times daily, or placebo. The primary end point was the proportion of patients who had a relapse by 2 years. Other end points included the annualized relapse rate, the time to confirmed progression of disability, and findings on MRI. RESULTS: The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons). The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group, as compared with 0.36 in the placebo group, representing relative reductions of 53% and 48% with the two BG-12 regimens, respectively (P<0.001 for the comparison of each BG-12 regimen with placebo). The estimated proportion of patients with confirmed progression of disability was 16% in the twice-daily BG-12 group, 18% in the thrice-daily BG-12 group, and 27% in the placebo group, with significant relative risk reductions of 38% with BG-12 twice daily (P=0.005) and 34% with BG-12 thrice daily (P=0.01). BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted hyperintense lesions (P<0.001 for the comparison of each BG-12 regimen with placebo). Adverse events associated with BG-12 included flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as well as decreased lymphocyte counts and elevated liver aminotransferase levels. CONCLUSIONS: In patients with relapsing-remitting multiple sclerosis, both BG-12 regimens, as compared with placebo, significantly reduced the proportion of patients who had a relapse, the annualized relapse rate, the rate of disability progression, and the number of lesions on MRI. (Funded by Biogen Idec; DEFINE ClinicalTrials.gov number, NCT00420212.) PMID: 22992073 
  
   

Preliminary results of the NINDS sponsored clinical trial, "Clinical Trial of Ceftriaxone in Subjects with ALS", were announced in August 2012.

• James Russell, DO was the Lahey Hospital & Medical Center principal investigator. A summary of the study status can be found on www.nealsconsortium.org.

Results of the NIH sponsored clinical trial, “Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF)” were presented at the 2012 International Stroke Conference on February 3, 2012.

• Matthew Tilem, MD was the Lahey Hospital & Medical Center principal investigator in conjunction with Sherif Labib, MD, Cardiology, and a total of 15 Lahey patients were enrolled into the trial. A summary of the results can be found on www.theheart.org. 

Results of the ANS and St. Jude sponsored clinical trial, “A Clinical Evaluation of bilateral stimulation of the subthalamic nucleus (STN) using the ANS Totally Implantable Deep Brain Stimulation System as an adjunctive treatment for reducing some of the symptoms of advanced, levodopa-responsive Parkinson’s disease that are not adequately controlled with medication” were published in the February 2012 journal of Lancet Neurol. ( Okun MS, Gallo BV, Mandybur G, Jagid J, Foote KD, Revilla FJ, Alterman R, Jankovic J, Simpson R, Junn F, Verhagen L, Arle JE, Ford B, Goodman RR, Stewart RM, Horn S, Baltuch GH, Kopell BH, Marshall F, Peichel D, Pahwa R, Lyons KE, Tröster AI, Vitek JL, Tagliati M; SJM DBS Study Group. Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease: an open-label randomised controlled trial. Lancet Neurol. 2012 Feb;11(2):140-9) 

• Jefferey Arle, MD, PhD of Neurosurgery was the principal investigator in conjunction with neurology sub-investigators Diana Apetauerova, MD and Janet Zani, NP.  A total of 8 Lahey Hospital & Medical Center patients were enrolled. An abstract of study results can be found on www.pubmed.org. 
• ABSTRACT: BACKGROUND: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. METHODS: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474.FINDINGS: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups.INTERPRETATION: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation.PMID: 22239915

Results of the Alzheimer's Disease Cooperative Study (ADCS), National Institute on Aging and the University of California San Diego sponsored clinical trial, “A Randomized, Double-Blind, Placebo-Controlled Trial of Valproate to Attenuate the Progression of Alzheimer's Disease (AD)” were published in the September 2011 journal of Neurology and the August 2011 journal of Arch Gen Psychiatry.  

• Yuval Zabar, MD was the principal investigator at Lahey Hospital & Medical Center and enrolled 8 Lahey patients.