[1H] Magnetic Resonance Spectroscopic Imaging to Identify Metabolic Abnormalities as Potential Biological Markers in Essential Tremor

Elan D. Louis, M.D., M.Sc.

Columbia University

Funded in September, 2000: $100000 for 2 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . FINDINGS . SELECTED PUBLICATIONS .

INVESTIGATOR BIOGRAPHIES

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Elan D. Louis, M.D., M.Sc.

Professor of Neurology and Epidemiology, Columbia University

HYPOTHESIS

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Hypothesis
Metabolic abnormalities are present in brain regions responsible for essential tremor (ET) and [1H] Magnetic Resonance Spectroscopic Imaging (MRS) may be used to detect these abnormalities. Identification of the abnormalities would lend new insight into the pathophysiology of ET, and, as biological markers, these abnormalities would have the potential to help clinicians establish diagnoses, follow disease progression, and assess response to therapies.

Goals:
1. To identify metabolic abnormalities in the cerebellum of ET cases compared with control subjects.
2. To determine whether the levels of metabolites correlate with disease duration or severity.
3. To determine whether there is an association between the clinical subtype of ET and the location of the metabolic abnormalities within the cerebellum.

Methods
Researchers will use a 1:1 matched case-control design, comparing 26 ET cases to 26 age-matched controls. Subjects will undergo a standardized clinical evaluation used in a previous study. This will include a 10-minute interview (collecting information on tremor duration) and a 10-minute videotaped tremor examination. The videotaped examination will include 12 tasks to bring out action tremor. Dr. Louis will then review the videotape and rate the tremors, using a 0-3 clinical rating scale.

Following a standard routine brain MRI protocol, multislice 1H MRSI data will be acquired by prescribing four 15-mm axial-oblique slices, which will be angulated such as to achieve full brain coverage, including the cerebellum, and other regions of interest. The major variables of interest will be the levels of metabolites (NAA, tCHO, LAC), expressed as ratios to creatine (NAA/tCR, tCHO/tCR, LAC/tCR). The distribution of each of these ratios will be examined and potential outliers will be identified. Descriptive statistics will be used to examine all variables when comparing cases and control subjects.

FINDINGS

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These studies demonstrate that there is a metabolic abnormality in the cerebellum in patients with essential tremor. This metabolic abnormality could represent underlying cell dysfunction or actual neuronal loss. In favor of the latter are recent postmortem data that demonstrate loss of Purkinje cells in essential tremor. In lay terms, these studies help us to understand the basic mechanisms that underlie a very common neurological disease, and they suggest that one of the main problems in the disease is degeneration of a part of the brain called the cerebellum.

 

SELECTED PUBLICATIONS

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Louis E.D., Zheng W., Mao X.L., and Shungu D.  Blood harmane is correlated with cerebellar metabolism in essential tremor: A pilot study. Neurology. 2007 Aug 7;69(6):515-20.

Louis E.D., Shungu D., Mao X., Chan S., and Jurewicz E.C.  Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: Implications for disease pathophysiology. Mov Disord 2004;19:672-677.

Louis E.D., Shungu D., Chan S., Mao X., Jurewicz E.C., and Watner D.  Metabolic abnormality in patients with essential tremor: A proton magnetic resonance spectroscopic imaging study. Neurosci Lett. 2002 Nov 15;333(1):17-20.