bounded by a membrane: the picture demonstrates that it is. The error is apparently not typographical; the statement is repeated in the text, though the adjacent text does con- tain an inconsistency as to which patients’ biopsies were studied by electron microscopy. Membranes may not, of course, be clearly visible in electron micrographs unless they run fairly perpendicular to the plane of section, so that a membrane of irregular course may be present but not visible in all its segments. In the illustration in question, a membrane is visible on all sides of the inclusion with the exception of a few brief stretches where ic is not clear.

The point is not completely trivial; the pathogenesis of Lafora disease is not understood. In neurons the polygluco- san accumulations are free in the cytoplasm. In skeletal muscle they are inside membrane-bound spaces [2]. The localization in liver has been harder to settle. Cells which, by light microscopy, seem to contain stored material, by electron microscopy have shown only masses of endoplas- mic reticulum filling the cytoplasm. We have suggested elsewhere [ 1 ] that the storage might in fact be largely within the endoplasmic reticulum and in the microbodies thought to be derived from it. It is thus of interest that Nishimura and his associates have found typical polygluco- san inclusions in the liver and that their picture shows one surrounded by a membrane.

One further stricture: it is not accurate to say that in skeletal muscle in Lafora disease, “ultrastructural findings include peroxisomes.” The characteristic granular-fila- mentous polyglucosan material in muscle cells is present in membrane-bound spaces by electron microscopy, while the sites of storage give cytochemical reactions characteris- tic of peroxisomes o n cryostat sections.

The authors also incorrectly cite Suzuki e t a1 [4] as hav- ing reported electron microscopic features (“branching filaments”) in hepatocytes in one case.

We agree that liver biopsy is a reliable (and even estab- lished) way of diagnosing Lafora disease, though the num- ber of cells involved may not be large, and use of the col- loidal iron stain may be necessary.

Montreal Neurological Institute 3801 University S t Montreal, Que, Canada H3A 284

References 1. Carpenter S, Karpati G, Andermann F, Jacob JC, Andermann

E: Lafora’s disease: peroxisomal storage in skeletal muscle. Neurology (Minneap) 24:531-538, 1074

2. Neville HE, Brooke MH, Austin JH: Studies in myoclonus epilepsy (Lafora body form): IV. Skeletal muscle abnormalities. Arch Neurol 30:466-474, 1974

3. Nishimura RN, Ishak KG, Reddick R, Porter R, James S, Bar- ranger JA: Lafora disease: diagnosis by liver biopsy. Ann Ncurol 8:409-415, 1080

4. Suzuki K, David E, Kutschmann B: Presenile dementia with “Lafora-like” intraneuronal inclusions. Arch Neurol25:69-79, 1971

Reply R. N. Nishimura, MD, K. G. Ishak, MD, PhD, R. Reddick, MD, R. Porter, MD, S. James, MD, and John A. Barranger, MD, P h D

We thank Drs Carpenter and Karpati for their comments. The purpose of our paper was to draw attention again to the usefulness of liver biopsy, a clinical aid often over- looked by neurologists, in diagnosing Lafora disease.

Our reference to Dr Suzuki’s paper concerned his- tochemical and ultrastructural characteristics of deposits in several tissues, including the liver, that were similar to our observations. Although they looked only at nerve and mus- cle, they reviewed the literature extensively. We cited the presence of peroxisomes in muscle biopsies of patients with Lafora disease as described by Dr Carpenter. We did not claim the deposit was within a peroxisome, only that these organelles were present.

We apologize for a typographical error. The patient in whose liver no inclusions were found under the electron microscope was actually Patient 4 (page 410, paragraph 2, line 2). Patient 3 and the accompanying photomicrographs are correctly labeled.

The contention that the deposit shown in Figure 4 is de- limited by a membrane is important. Our interpretation is that the density surrounding the deposit represents com- pressed endoplasmic reticulum. Since it is discontinuous around the particle and in several places appears to mesh with endoplasmic reticulum from adjacent areas, we do not think this is a membrane. In our experience, none of the deposits in liver of patients with Lafora disease is mem- brane delimited. Differential ultrastructural staining tech- niques would go far in settling this controversy. Tissue is available for this purpose.

Developmental and Metabolic Neurology Branch National Institute of Neurological and Communicative Disorders and Stroke Bethesda, M D 20205

L-DoDa-Resis tan t Parkhsonism Due to DoDa Decarboxylase Deficienc;? Joseph Jankovic, M D

The excellent article by Drs Melamed, Hefti, and Wurtman [ 13, suggesting that nonaminergic decarboxylase-containing interneurons or striatal efferent neurons may play an im- portant role in decarboxylation of exogenous L-dopa, raises some important clinical points. Recently we evaluated three patients with advanced progressive supranuclear palsy [3J who were clinically unresponsive to large doses (4 to 6 tablets per day) of Sinemet 2 5 / 2 5 0 and who showed a marked although transient improvement of axial rigidity, dysarthria, and gait disorder, without change in ophthal- moparesis, with small doses of bromocriptine (10 to 15 mg per day). Sinemet was completely discontinued in two of the patients and was markedly reduced in the third. A

64 Annals of Neurology Vol 10 No 1 July 1981

similar situation is occasionally encountered in parkinson- ian patients unresponsive to large doses of Sinemet, who rarely respond to even small doses of a dopamine agonist.

It is possible that in some degenerative disorders (e.g., progressive supranuclear palsy), exogenous L-dopa cannot be decarboxylated because of selective damage to all o r most of the striatal elements that contain dopa decar- boxylase [2]. In this situation, direct stimulation of the rel- atively intact postsynaptic dopamine receptors by bromo- criptine, a direct dopamine agonist, on the striatal efferent neurons may result in clinical improvement.

Baylor College of Medicine Texas Medical Center Houston, T X 77030

References 1. Melamed E, Hefti F, Wurtman RJ: Nonaminergic striatal

neurons convert exogenous L-dopa to dopamine in parkin- sonism. Ann Neurol 8:558-563, 1980

2 . Mendell JR, Chase TN, Engel WK: Modification by L-dopa of a case of progressive supranuclear palsy with evidence of defec- tive cerebral dopamine metabolism. Lancet 1:593-594, 1970

3. Steele JC, Richardson JC, Olszewski J: Progressive supranu- clear palsy. Arch Neurol 10:333-359, 1964

Rearranged Equation for Determining Local Cerebral Glucose Utilization Minoru Tomita, MD, and Fumio Gotoh, M D

The quantitative determination of local cerebral glucose utilization in vivo in both animals [ l , 3 , 4 ] and human sub- jects [2] is without doubt one of the outstanding achieve- ments of the last decade. I t is founded on a number of basic sciences, the autoradiographic technique, and computed tomography. The impact of such determination of local cerebral metabolism on clinical medicine cannot be over- estimated. The equation, ingeniously derived by Sokoloff et a1 [4 ] by mathematical analysis of a model of the biochemical behavior of [ 14C]deoxyglucose and glucose in the brain, is written as:

Since k: and k: are the constants and T is the specified time, this equation may be rearranged into a much simpler form, as follows:

where LC is the lumped constant (AV”,,,,)/(+V,K”,. This rearranged form may not only save computation

time, but also may help to alleviate fear or allergic reactions among readers or audiences grappling with the complicated mathematical equation.

Department of Neurology Keio University School of Medicine 33 Shinanomachi, Shinjuku-ku Tokyo 160, Japan

References 1. Goochee C, Rasband W, Sokoloff L: Computerized densi-

tometry and color coding of [14C]deoxyglucose autoradio- graphs. Ann Neurol 7:359-370, 1980

2. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE: Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D- glucose: validation of method. Ann Neurol 6:371-388, 1979

3. Sokoloff L Mapping of local cerebral functional activity by measuremenr of local cerebral glucose utilization with [‘%I deoxyglucose. Brain 102:653-668, 1979

4. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada 0, Shinohara M: The [‘*C]deoxy- glucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the con- scious and anesthetized albino rat. J Neurochem 28:897-916, 1977

Notes and Letters 65