Schmahmann Lab Update

Massachusetts General Hospital Ataxia Unit and


Laboratory for Neuroanatomy and Cerebellar Neurobiology


Annual Update to our Friends and Donors


Jeremy D. Schmahmann, M.D.

July 29 2014


The MGH Ataxia Unit and Laboratory for Neuroanatomy and Cerebellar Neurobiology continue to thrive. The Ataxia Unit is the centerpiece of our clinical, research, and teaching effort. We provide care to approximately 1,000 patients with all forms of cerebellar disorders. Our patients and families come from the Boson area and throughout New England, as well as across the US and internationally.  I am joined by Drs. Vik Khurana and Steve Masssaquoi, our Ataxia Fellow Dr. Rob Moccia who just completed two successful years of Ataxia Fellowship and is now moving into the lab for the next few years, and Unit Coordinator Marygrace Neal.  Together with colleagues in many disciplines, we strive to cure diseases when possible, and improve the lives of our patients and families. Partners neurology residents (MGH and the Brigham and Women’s Hospital) and Harvard medical students rotate through the Unit. We hold teaching conferences that are open to other movement disorder specialists, cognitive neurologists, and colleagues from the fields of speech, occupational and physical therapy, and we collaborate with the physiatry team at the Spaulding Rehabilitation Hospital.

In the Lab our two main areas of study are i) neuroanatomy  – how the brain is wired up to enable motor and cognitive function, and  ii) cerebellar neurobiology – the causes and clinical manifestations of disorders of the cerebellum. Dr. Franziska Hoche, our current post-doctoral research fellow, was funded through MINDlink for the first year in the Lab. She has subsequently received awarded grant support from the MGH Committee on Research, the National Ataxia Foundation, and the Ataxia Telangiectasia (AT) Children’s Project. Franziska is one of the few experts in the world on the cognitive and emotional manifestations in children with AT. She is continuing to studying intellectual function and social cognition in AT and the ataxias in adults, and she recently received a travel award from the American Neurological Association (ANA) to present her work at its 2014 meeting in Baltimore. A student visiting the Lab from Spain, Xavier Guell, worked with us to develop new ways to identify why some people with cerebellar problems have difficulty expressing themselves or understanding nuances in language. Xavier won the Masao Ito award for this work at the 6th International Congress of the Society for Research on the Cerebellum in Rome, Italy earlier this month. Four of the Lab’s 8 poster presentations at the in March 2014 won merit-based travel awards.

David Lin joined the lab as a Harvard medical student two years ago, and is now a Partners neurology resident. David and research assistant Katherine Hermann (supported by the Birmingham Foundation and MINDlink), worked with me to publish a review laying out the problems with current approaches to the diagnosis of Multiple System Atrophy of the Cerebellar type (MSAc). We have now completed a study of the course of patients with MSAc whom I have followed over the past 20 years, in which we simplify the diagnostic criteria for MSAc. Early diagnosis is essential to the development and implementation of new approaches to treatment. David and Katherine received travel awards to present this work both to the National Ataxia Foundation Investigators’ in Las Vegas earlier this year, and to the forthcoming ANA meeting. We are developing new ways to use brain MRI scans to diagnose MSAc early in its course, and I am assisted in this effort by my Lab Manager, Jason MacMore who is supported by MINDlink, and a team of research assistants and students. Vik Khurana’s work at the Whitehead Institute using yeast cell and stem cell models of disease holds great promise for understanding the biology of MSAc and developing and testing treatments, and he has received funding from the MSA Coalition to further explore this approach. Both he and I were invited to join a select group of investigators at the forthcoming Global MSA Research Roadmap Meeting in Las Vegas.

We described new genetic diseases over the past year. Working with colleagues in endocrinology and genetics, we found the genetic basis of the Gordon Holmes Syndrome that affects three of our patients. With colleagues in mitochondrial biology we found the genetic basis of Perrault syndrome, which has not previously been described in men with ataxia. We cannot yet cure these newly defined genetic disorders, but knowing what they are helps take the sting out of being in the dark, and allows us to focus on alleviating symptoms, while working to fix the underlying biology.

We are making strides understanding how the cerebellum is connected to the rest of the brain, and how the cerebellum is involved in mental illness. Together with MGH colleagues including Dr. Catherine Stoodley, my previous research post-doctoral fellow now at the American University in Washington DC, we studied people with cerebellar strokes and found that damage to different parts of the cerebellum causes ataxia or cognitive changes depending on the location of the damage. With colleagues at the Beth Israel Deaconess Medical Center we are studying how transcranial magnetic stimulation to the cerebellum improves symptoms in people with schizophrenia, and how cerebellar stimulation influences the way different areas of the cerebral hemispheres communicate with each other.  The Sidney Baer Jr., Foundation is now supporting this work, but this project would not have started without the support of MINDlink.

As members of the US-wide Cooperative Ataxia Group we are conducting a natural history study of the spinocerebellar ataxias (SCAs) – notably SCA 1, 2, 3 and 6. We are following over 40 patients, the MGH subset of the 345 patients studied to date. This work follows our study published last year led by a research assistant (now medical student) Laura Horton, of a large family with SCA 7 followed at the MGH for over 25 years.

We are using brain imaging to define structural changes in the cerebellum in ataxic disorders in order to facilitate early diagnosis, and to serve as a biomarker to measure improvements when treatments are available. With our research assistant, Richard Juelich, in collaboration with colleagues who developed a mouse model of SCA 1 (Huda Zoghbi), we identified changes in the mouse cerebellum in SCA 1 using a form of MRI called diffusion tensor imaging (DTI). We are planning to adopt this approach now in patients with SCA 1. With colleagues at Children’s Hospital Boston (Emi Takahashi and Ellen Grant) we have provided new insights into the organization of the cerebellar cortex in adults and children using DTI, and we have shown how cerebellar cortex evolves in the developing brain. We are using the new Connectome scanner to study brain organization in humans and animals. Building on our previous anatomical work on brain connectons we are collaborating with colleagues at Boston University to study new findings from MRI of a grid organization of white matter pathways published by one of our collaborators (Van Wedeen).

Other recent publications include the Cerebellum section in the new edition of The Netter Collection of Medical Illustrations (Elsevier), and chapters on cognition and cerebellar disorders in a number of monographs. We have also co-edited and contributed to the 4-volume text The Handbook of the Cerebellum and Cerebellar Disorders (Springer), and Cerebellar Disorders in Children (MacKeith).

Prevention and cures are our goal. In 2004 we showed that immune modulation cures young adults whose cerebellum is attacked by Ebstein Barr virus (glandular fever / infectious mononucleosis, or “mono”). In a case discussion in September 2013 in the New England Journal of Medicine (NEJM) we described how young adults with this post-infectious cerebellitis are incapacitated from motor and cognitive impairments, and if they are not treated early on, these problems persist, but if they are treated, symptoms melt away in days. A college student from Rhode Island affected by this illness early last month became progressively incapacitated over a period of two weeks. His family found the NEJM article online, brought him to us at the MGH, and within days of treatment he made a remarkable recovery. This young man’s return to full health is a result of collaborative clinical and research work, and the teams of investigators, researchers and students dedicated to this mission.

In the coming year we will continue to pursue these lines of study. We will also share Fellows with the MGH Neuropsychiatry, Huntington Disease (HD), Dystonia, Movement Disorders, and General Neurology programs because ataxias share features with these other conditions (e.g., SCA 17 resembles HD), and we are setting up collaborations with the ALS program because ALS biology is relevant to SCA2, AOA and hereditary spastic paraplegias. We will initiate a study with our rehabilitation specialists to start treatment trials using brain stimulation in ataxia patients, we will be studying cerebellar agenesis and hypoplasia (underdevelopment) in great detail from all clinical aspects including its genetic basis. We will continue to pursue anatomical investigations with the Connectome scanner in patients with cerebellar and other disorders.

All this work is heavily dependent on the ongoing support of our MINDlink donors. With your commitment to this effort we will be well placed to make strides in understanding, treating, and curing disorders of the cerebellum and related conditions. Simply put, we can’t do this without you.

Thank you.


Jeremy D. Schmahmann, MD

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