• • •Examination of gait kinematic and ambulation parameters for Multiple Sclerosis
•  Investigations in Multiple Sclerosis Clinical Epidemiology, "Rhode Island Multiple Sclersosis Study"
•  Stroke Robotic and neuromodulation upper extremity rehabilitation
•  Development of a Functional electrical stimulation system to address
•  Analysis of Cortical physiology for freezing of gait in Parkinson's, near infrared-spectroscopy
• • Robot interventions for Parkinson's Disease Freezing of Gait
• • Neuroprotection in Multiple Sclerosis and Animal models
• •
• • Mild Traumatic Brain Injury: Impact on Attention, and Motor Control

Stroke rehabilitation Clinical Trials Phase II/III in Robotic Neurorehabilitation
[Upper extremity with MIT-Manus system]

Robotic-assisted rehabilitation is a promising intervention for reversing upper extremity impairment in chronic stroke. Stroke is the leading cause of disability for older Americans. Much of this disability can be traced to the lasting neurological impairments in stroke survivors, particularly when the functional deficits affect the arm and hand. Currently there are no definite rehabilitative therapies for chronic stroke patients. Accordingly, there is a strong clinical impetus to develop interventions to restore neurological function, including during the chronic period of stroke recovery. Innovations in clinical robotic technology in conjunction with advances in the understanding of the potential for neurological recovery in the chronic stages of stroke now make it possible to test a promising new therapy using task-specific, robot-assisted neurorehabilitation for the upper-limb in chronic stroke patients. Preliminary studies have examined over 250 stroke patients using earlier version of the MIT-manus robot.

I am the principal investigator for a $4.8 mil phase II/III multi-centered clinical trial funded by the Veteran's Administration (Clinical Science Program and Rehabilitation Research and Development Services) to test the most advanced MIT-manus system (modules which include training of the shoulder, elbow, wrist and hand) in chronic stroke patients with moderate to severe upper-limb impairment. The trial was initiated in November of 2006. The 4 sites include VA Medical Centers in Baltimore MD, Gainesville FL, and Seattle WA, and West Haven CT. The study plans to enroll approximately 160 subjects over 3 years. As of July 2008, over a 100 stroke subjects have participated. This randomized-controlled trial for stroke rehabilitation using robotics has received various regional and national media coverage.

Multiple Sclerosis Clinical Pilot Studies Robotic Neurorehabilitation
[Lower extremity with Lokomat]

Ongoing walking impairment is a clinical problem and important source of disability for people with MS. MS patients even at the earliest stages of disease have observable gait problems, and over the lifetime of the disease, the majority of MS patients will progressively decline in their gait function. Robot-assisted rehabilitative devices are a promising technology for improving impairment in the lower extremity. We have completed studies on over 20 patients with MS using the Lokomat (a robot drive lower extremity orthotic) or the Ankle-bot (a device developed at MIT by Hermano Igo Krebs that assists with ankle flexion-extension and supination-pronation). These studies have systematically characterized gait abnormalities, as well as changes in strength, quality of life, fatigue and disability in MS following robot-assisted interventions.


Neuroprotection in Multiple Sclerosis and animal models

It is becoming increasingly clear that Multiple Sclerosis pathology involves significant neurodegeneration, and it is the neurodegeneration that most contributes to the ongoing disability in MS. We have conducted a number of preclinical studies for neuroprotection using experimental allergic encephalomyelitis (EAE), an animal model of MS, while at Yale University in the Laboratory of Dr. Stephen Waxman. In this model we have developed a well-calibrated and reproducible model of axon loss with the optic nerve and spinal cord tracts. We have been able to show robust axonal neuroprotection in EAE animals using sodium channel blocking agents. In addition there was improvement of spinal cord electrophysiological conduction and clinical paralysis compared to untreated EAE. The majority of the current FDA-approved agents for the treatment of Multiple Sclerosis act on immunomodulatory pathways. We have ongoing interest in conducting a clinical trial for neuroprotection in MS.

Investigations in Multiple Sclerosis Clinical Epidemiology

Multiple sclerosis is a heterogeneous chronic disease, which neither the course of the disease or a patient's response to therapy is predictable. As a result treatment patterns for MS can vary considerably. A systematic assessment aimed at understanding the current state of MS healthcare is critical to determining treatment patterns, including gaps in care and can potentially provide useful information to improve the regional and national healthcare delivery for people with MS. One approach that I have been pursing is to assess MS care using the North American Research Committee on Multiple Sclerosis (NARCOMS) Database to examine the delivery and pattern of MS healthcare. The NARCOMS patient registry is the largest and most comprehensive registry of MS patients in the world with over 24,000 active participants, and we have initiated a series of studies to further investigate the current state of MS epidemiology using this database, with a particular emphasis on veteran care.

in development

Rhode Island Multiple Sclerosis Study (RIMMS)

As an initial study of the Brown University Genebank initiative and in collaboration with Dr. Stephen Buka (Professor of Epidemiology), we have initiated a prospective, community-based longitudinal study of Multiple sclerosis in the state of Rhode Island.

Much of the understanding of multiple sclerosis (MS) epidemiology and clinical course has been derived from cohort studies collected outside the United States or from short-term pharmaceutical clinical trials. These sources of information may have inherent biases that limit their usefulness to typical patients in the community. A population-based study in the US that aims to combine rich epidemiologic and clinical data is critical to advancing both scientific understanding and providing accurate information to guide treatment. The RIMSS study proposes to establish a prospective population-based cohort study of multiple sclerosis (MS) in Rhode Island. Overall goals include enumerate and provide accurate data on incident and prevalent cases of MS and clinically isolated syndrome and collect demographic and diagnostic data from medical records.
Evolving phases of the study will include baseline assessments on a random stratified sample of approximately 400 new incident and prevalent cases of MS and CIS to approximate the longitudinal course of these conditions using a balanced and informative cross-sectional design. In doing so, we will be able to describe the prevalence of physical disability, cognitive disability, symptomatic areas, and magnetic imaging changes by disease subtypes (relapsing-remitting MS, secondary progressive MS, primary progressive MS, CIS) and duration of disease, and treatment with disease modifying agents. Finally, we will initiate the longitudinal assessments of the 400 subjects with comprehensive baseline assessments. This phase will also enroll and follow the unaffected siblings to examine the development of MS or other autoimmune disorders. The scope of multidisciplinary study provides an opportunity to build a unique national MS cohort based in Rhode Island to clearly capture critical information in order to better understand the clinical and epidemiological sciences MS.

Mild traumatic brain injury: impact on attention, cognition and motor control
Investigators: Stephen Correia, Leigh Hochberg, Albert Lo, Stephen Mernoff, Michael Worden.

There is currently no brief, reliable, valid, and easily administered test to gauge attention and executive cognitive capabilities following mild traumatic brain injury (mTBI).
mTBI occurs frequently in sports and in combat environments and is associated with declines in attention, mental processing speed, reaction time, and executive functions, that are important in sports and crucial in combat situations where detection and reaction to threatening vs. non-threatening targets is vital. To date, no objective measure has been widely adopted to predict safe and efficacious resumption of play or combat duty. The current gold standard for assessing cognitive functioning following mTBI is neuropsychological testing, which can take up to three hours to administer and have uncertain validity for predicting successful return action. We plan to develop a brief, reliable, valid, and easily administered computerized assessment of attention, cognition and motor reaction.

Gianfrancesco MA, Triche EW, Fawcett JA, Labas MP, Patterson TS, Lo AC. (2011). Speed- and cane-related alterations in gait parameters in individuals with multiple sclerosis. Gait and Posture. 33:140-142.

Wier LM, Hatcher MS, Triche EW, Lo AC. (2011). Effect of Body-Weight Supported Treadmill Training with and without Robotic Assistance on Quality of Life for People with Multiple Sclerosis. Journal of Rehabilitation Research and Development. 48: (In Press).

Schmid AA, Kapoor JR, Miech EJ, Kuehn D, Dallas MI, Kerns RD, Lo AC, Concato J, Phipps M, Couch CD, Moran E, Williams LS, Goble LA, Bravata DM. (2010). A Multidisciplinary Stroke Clinic for the Outpatient Care of Veterans with Cerebrovascular Disease. Journal of Multidisciplinary Healthcare. (In press).

Wagner TH, Lo AC, Peduzzi P, Bravata DM, Huang GD, Krebs HI, Ringer RJ, Federman DG, Richards LG, Haselkorn JK, Wittenberg GF, Volpe BT, Bever CT, Duncan PW, Siroka A, Guarino P. (2011). An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke. Stroke (In Press).

Chumbler NR, Williams LS, Wells CK, Lo AC, Nadeau S, Peixoto AJ, Gorman M, Boice JL, Concato J, Bravata DM. (2010). Derivation and Validation of a Clinical System for Predicting Pneumonia in Acute Stroke. Neuroepidemiology. 34(4):193-9.

Bravata DM, Wells CK, Lo AC, Nadeau S, Melillo J, Chodkowski D, Struve F, Williams LS, Peixoto AJ, Gorman M, Goel P, Acompora G, McClain V, Ranjbar N, Tabereaux PB, Boice JL, Jacewicz M, Brass LM, Concato J. (2010). Processes of Care Associated with Acute Stroke Outcomes. Archives of Internal Medicine. 170(9):804-810.

Bravata DM, Concato J, Fried T, Ranjbar N, Sadarangani T, McClain V, Struve F, Zygmunt L, Knight H, Lo A, Richerson G, Gorman M, Williams LS, Brass LM, Agostini N, Mohsenin V, Roux F, Yaggi HK. (2010). Auto-Titrating Continuous Positive Airway Pressure for Patients with Acute Transient Ischemic Attack: A Randomized Feasibility Trial. Stroke. 41(7):1464-70.

Lo AC, Chang VC, Gianfrancesco MA, Friedman JH, Patterson TS, Benedicto DF. (2010). Reduction of freezing of gait in Parkinson's disease by repetitive robot-assisted treadmill training. Journal of Neuroengineering and Rehabilitation. 7(1): 51-8.

Schmid A, Wells CK, Concato J, Dallas MI, Lo AC, Nadeau S, Williams LS, Peixoto A, Gorman M, Boice JL, Struve F, McClain V, Bravata DM. (2010). Prevalence, Predictors, and Outcomes of Post-Stroke Falls in the Acute Hospital Setting. Journal of Rehabilitation Research and Development. 47(6):553-62.

Lo AC, Guarino P, Richards LG, Haselkorn JK, Wittenberg GF, Federman DG, Ringer RJ, Wagner TH, Bever CT, Krebs HI, Volpe BT, Bravata DM, Duncan PW Corn BH, Maffucci AD, Nadeau MD, Conroy, Powell JM, Huang GD, Peduzzi P. (2010). Robot-assisted therapy for long-term impairment after stroke. New England Journal of Medicine. 362(19):1772-1783.

Lo AC, Guarino P, Krebs HI, Volpe BT, Bever CT, Duncan PW, Ringer RJ, Wagner TH, Richards LG, Bravata DM, Haselkorn JK, Wittenberg GF, Federman DG, Corn BH, Maffucci AD, Peduzzi P. (2009). Multi-center Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS. Neurorehabilitation and Neural Repair. 23:775-785.

Krebs HI, Dipietro L, Levy-Tzedek S, Fasoli S, Rykman A, Zipse J, Fawcett J, Stein J, Poizner H, Lo AC, Volpe B, Hogan N. (2008). A Paradigm-Shift: Rehabilitation Robotics. IEEE--Engineering in Medicine and Biology. 7:61-70.

Lo AC. (2008). Advancement of therapies for neuroprotection in multiple sclerosis. Expert Reviews of Neurotherapeutics. 8(9):1355-1366.

Lo AC, Triche EW. (2008). Improving gait in multiple sclerosis using robot-assisted, body weight supported treadmill training. Neurorehabilitation and Neural Repair. 22:661-671.

Lo AC, Hadjimichael O, Vollmer TL. (2005). Treatment patterns of multiple sclerosis patients: A comparison of veterans and non-veterans using the NARCOMS registry. Multiple Sclerosis. 11:33-40.

Hains BC, Saab CY, Lo AC, Black JA, Waxman SG. (2004). Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal recovery, and improves functional motor recovery after contusion SCI. Experimental Neurology. 188:365-377.

Craner MJ, Damarjian TG, Liu S, Hains BC, Lo AC, Black JA, Newcombe J, Cuzner ML, Waxman SG. (2004). Sodium channels contribute to microglial and macrophage activation and function in EAE and MS. Glia. 49:220-229.

Craner MJ, Hains BC, Lo AC, Black JA, Waxman SG. (2004). Co-localization of sodium channel Na 1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain. 127: 294-303.

Craner MJ, Lo AC, Black JA, Baker D, Newcombe J, Cuzner L, Waxman SG. (2003). Annexin II/p11 is upregulated in purkinje cells in EAE and MS. NeuroReport. 14:555-558.

Craner MJ, Lo AC, Rasband MN, Black JA, Waxman SG. (2003). Abnormal sodium channel distribution in the optic nerve in a model of inflammatory demyelination. Brain. 126:1552-1561.

Craner MJ, Kataoka Y, Lo AC, Black JA, Baker D, Waxman SG. (2003). Temporal course of upregulation of Nav1.8 in in purkinje neurons parallels the progression of clinical deficit in EAE. Journal of Neuropathology and Experimental Neurology. 62:968-975.

Lo AC, Saab CY, Black JA, Waxman SG. (2003). Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. Journal of Neurophysiology. 90: 3566-3571.

Lo AC, Black JA, Waxman SG. (2002). Neuroprotection of axons with phenytoin in experimental allerigic encephalomyelitis. NeuroReport. 13:1909-1912.

Mattson DH, Lo AC, Auld E. (2002). Disorders that Mimic Multiple Sclerosis. Multiple Sclerosis Quarterly Report 21:12-16.

Gould TW, Burek MJ, Ishihara R, Lo AC, Prevette D, Oppenheim RW. (1999). Androgens rescue avian embryonic lumbar spinal motoneurons from injury-induced but not naturally occurring cell death. Journal of Neurobiology. 41:585-95.

Houenou LJ, Oppenheim RW, Li L, Lo AC, Prevette D. (1996). Regulation of spinal motoneuron survival by GDNF during development and following injury. Cell and Tissue Research. 286:219-223.

Lo AC, Houenou LJ, Oppenheim RW. (1995). Apoptosis in the nervous system: morphological features, methods, pathology and prevention. Archives of Histology and Cytology. (Special Edition) 58:139-149.

Oppenheim RW, Houenou LJ, Johnson JE, Leu-Fen HL, Li L, Lo AC, Newsome AL, Prevette DM, Wang S. (1995). Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature. 373:344-346.

Lo AC, Li L, Oppenheim RW, Prevette D, Houenou LJ. (1995). Ciliary neurotrophic factor (CNTF) promotes survival of spinal sensory neurons following axotomy but not during the period of programmed cell death. Experimental Neurology. 134:49-55.

Houenou LJ, Prevette DM, Lo AC, Li L, Oppenheim RW. (1994). Motor neuron tropic agents: In vivo studies during embryogenesis. Muscle Nerve. 1:S20.

Houenou LJ, Lo AC, Yan Q, Oppenheim RW. (1994). Naturally occurring and axotomy-induced motoneuron death and its prevention by neurotrophic agents: A comparison between chick and mouse. Progress in Brain Research. 102:217-226.

* Providence Veterans Administration Hospital
* The Center for Restorative and Regenerative Medicine, PVAMC
* Admission Committee, Warren Alpert School of Medicine at Brown University
• VA Advisory Committee, Secretarial Appointee, VA RRD Scientific Merit Review Board, Neurological Dysfunction/ Spinal cord injury.
• Executive steering committee, Joyce D. and Andrew J. Mandell Multiple Sclerosis Center
• Brown Biomedical Engineering Executive Advisory Council.
• VA Multiple Sclerosis Center of Excellence, Research Advisory Panel
• American Academy of Neurology, Author Panel for practice parameter guidelines in Multiple Sclerosis
• American Society for Neurorehabilitation
• Scientific Steering Committee for North American Research Committee on Multiple Sclerosis (NARCOMS)