identified a severe reduction of the 300-kDa fragment and a virtual absence of the 80-kDa fragment. Similar findings were reported in other families with muta- tions in FKRP gene. 5 Laminin-2 is an extracellular matrix protein that binds to the -dystroglycan in the sarcolemma. This binding plays a key role in the as- sembly of the extracellular matrix components. We can suggest that hypoglycosylation of the -dystroglycan due to FKRP mutations could alter binding or assem- bly of the extracellular components causing an abnor- mal staining of the laminin-2. The difference between the immunocytochemical and immunoblot analyses could suggest that mutations in FKRP gene result in the altered processing, epitope masking, or abnormal folding of the laminin-2 polypeptide chain. 5 The identification of FKRP as responsible for LGMD2I and MDC1C provided us insights into the molecular mechanism of muscular dystrophy and the roles of glycosylation on -dystroglycan. However, there remain a number of questions to be solved, in- cluding the role of FKRP on glycosylation of -dystro- glycan and the variable laminin-2 expression. Acknowledgment The authors thank all sequence team members in the Department of Molecular Biology, Keio University School of Medicine. References 1. Neuromuscular disorders: gene location. Neuromuscul Disord 2003;13: 97–108. 2. De Sandre-Giovannoli A, Chaouch M, Kozlov S, et al. Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autoso- mal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disor- der Type 2) and Mouse. Am J Hum Genet 2002;70:726 –736. 3. Driss A, Amouri R, Ben Hamida C, et al. A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3. Neuromuscul Disord 2000;10:240 –246. 4. Brockington M, Blake DJ, Prandini P, et al. Mutations in the fukutin- related protein gene (FKRP) cause a form of congenital muscular dystro- phy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 2001;69:1198 –1209. 5. Brockington M, Yuva Y, Prandini P, et al. Mutations in the fukutin- related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Hum Mol Genet 2001;10:2851–2859. 6. Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, et al. Human dys- troglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization. Hum Mol Genet 1993;2: 1651–1657. 7. Ervasti JM, Campbell KP. Membrane organization of the dystrophin- glycoprotein complex. Cell 1991;66:1121–1131. 8. Hayashi YK, Ogawa M, Tagawa K, et al. Selective deficiency of alpha- dystroglycan in Fukuyama-type congenital muscular dystrophy. Neu- rology 2001;57:115–121. 9. Kano H, Kobayashi K, Herrmann R, et al. Deficiency of alpha- dystroglycan in muscle-eye-brain disease. Biochem Biophys Res Com- mun 2002;291:1283–1286. 10. Grewal PK, Holzfeind PJ, Bittner RE, Hewitt JE. Mutant glycosyl- transferase and altered glycosylation of alpha-dystroglycan in the myo- dystrophy mouse. Nat Genet 2001;28:151–154. Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy Fernando L. Pagan, MD; John A. Butman, MD, PhD; James M. Dambrosia, PhD; and Mark Hallett, MD Abstract—The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects. The authors’ data suggest that the decreased NAA/Cr and NAA/Cho ratios within the cerebellum may represent an abnormality in neuronal function. NEUROLOGY 2003;60:1344 –1347 MR spectroscopy (MRS) can make in vivo, noninva- sive inferences about the neuropathology of CNS dis- orders. We used a multivoxel, multislice, multi- metabolite, MRS-imaging program developed at the National Institutes of Health (NIH) 1,2 to evaluate es- sential tremor (ET). We measured N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Our main objective was to compare NAA/Cr and NAA/Cho ratios within the cerebellum of ET patients with those from healthy volunteers. See also page 1232 From the Medical Neurology Branch (Drs. Pagan and Hallett) and Biostatistics Branch (Dr. Dambrosia), National Institutes of Health, National Institute of Neurological Disorders and Stroke; Diagnostic Radiology Department (Dr. Butman), Warren G. Magnuson Clinical Center, Bethesda, MD. Received May 8, 2002. Accepted in final form February 12, 2003. Address correspondence and reprint requests to Dr. Mark Hallett, NIH, NINDS, HMCS, Building 10, Room 5N226, 10 Center Drive, MSC1428, Bethesda, MD 20892-1428; e-mail: hallettm@ninds.nih.gov 1344 Copyright © 2003 by AAN Enterprises, Inc.