LETTERS

Tamoxifen for Brain Metastases from Breast Cancer Stig €3. Hansen, MD,” Helene Galsgird, MD,” Finn E. von Eyben, MD, PhD,* Vagn Westergaard-Nielsen, MD,t and Jacob Wolf-Jensen, MDf

Patients with untreated brain metastases from breast cancer usually survive less than 2 months. Neurological symptoms from brain metastases may be palliated by whole-brain irradi- ation or by adrenocorticoid therapy, but after such treat- ment, median survival has been only slightly extended by 2 to 8 months. Patients with a solitary brain metastasis without evidence of cancer outside the brain may undergo resection, irradiation, or both, but few obtain long-term survival.

We used tamoxifen as the sole treatment in a patient with brain metastases from breast cancer. The patient had under- gone a left mastectomy for cancer at age 38 and had had a tumor in the mastectomy scar for some years when admitted at age 68 because of a generalized tonic-clonic seizure. All findings from neurological examination were normal, and the lesion in the mastectomy scar measured 4 cm in diameter. An electroencephalogram (EEG) showed bifrontotemporal delta waves and diffuse and temporal theta and sharp waves; a technetium scintigram of the brain revealed multiple le- sions with increased activity. She was given tamoxifen I0 mg three times daily orally and was discharged feeling well. She did not undergo irradiation, operation, chemotherapy, or anticonvulsant treatment.

Four months later, a computed tomographic (CT) scan of the brain showed several hyperdense lesions measuring 1 to 2 cm in diameter in the occipital region, as well as several smaller lesions in the frontal and right temporal regions. Serum concentration of carcinoembryonic antigen (CEA) was 15.4 pg/L (upper limit of normal, < 1.5).

By 13 months, the tumor in the mastectomy scar had disappeared and she had had no further seizures. Another EEG revealed marked improvement and a CT scan showed the brain metastases had decreased in size. Serum CEA con- centration was 1.8 pdL and serum concentration of tamoxi- fen was 400 pg/L as measured by chromatographic assay, suggesting good compliance. Tamoxifen was continued at 20 mg twice daily and she remained well without side effects for a further 14 months. A third C T scan showed the brain metastases had not increased in size or number, and a fourth showed substantial regression of most lesions.

In contrast to endocrine treatment, chemotherapy has had minimal effect on brain metastases from breast cancer. CCNU, a lipophilic drug, passes freely through the blood- brain barrier. However, in a series of patients treated with CCNU, vincristine, and methotrexate, only half of the pa- tients improved objectively and their median survival of 9 months indicates the treatment had only a minor impact {3}. In another series, the median survival was similar in spite of a high rate of remission [4].

Multiple brain metastases disappeared after tamoxifen and prednisone treatment in another woman with metastatic

breast cancer, and she remained neurologically stable for over 30 months [I]. Soft-tissue metastases disappeared ir,( that patient as well as in our patient, indicating that the can- cer in both was hormone sensitive. Similarly, brain metas- tases in other patients regressed objectively after treatment with fluoxymesterone [ 3 ] or bromocriptine C21. Tamoxifen and other hormonal treatments should be studied further in patients with brain metastases from hormone sensitive breast cancer or estrogen-receptor-positive tumors.

“Depar.tment o f lntwnal Medicine Cauntj, Hospital in Nakskozi fDepa:ytment of Diagnostic Radiology Central Hospital Nykobing Fahter $Department of Clinical Chemistry Finseninstitutet Copenbagen. Denmark

References 1. Carey RW, Davis JM, Zervas NT: Tamoxifen-induced regression

of cerebral metastases in breast carcinoma. Cancer Treat Rep 65:793-795, 1981

2. Gr,soli F, Vincentelli F, Foa J, et al: Effects of bromocriptine on brzin metastasis in breast cancer. Lancer 2:745, 1981

3. Hiidebrand J, Birhaye J. Wagenknecht L, et al: Combination chemotherapy with CCNU, vincristine, and methotrexate in pri- miry and metastatic brain rumors. Eur J Cancer 11:585-587, 1975

4. Rosner D, Nemoro T: Blood-brain barrier a myth? Chemorher- apy of central nervous system (CNS) metastases in breast cancer: a pilot study. Proc Am Assn Cancer Res 24:140, 1983

5 . Sparrow GEA, Rubens R: Brain metastases from breasr cancer: clinical course, prognosis, and influence of treatment. Clin Oncoi 7.291-301, 1381

M[onocular Oscillopsia Secondary to Lens Subluxation Roiald S. Murray, MD, and E. T. Ajax, M D

0so:illopsia usually indicates an underlying and untreatablt: neiirological disease process [ 13. We present the following case as an example of a treatable cause of oscillopsia.

A 58-year-old physician sustained a blunt injury to his right eye with mimimal external signs of trauma. Im- mediately following the incident, he experienced oscillopsia. The visual illusion was precipitated by initiating an abrupt change in axis of gaze. This occurred in any direction but was most marked with high-velocity horizontal saccades and was less evident with smooth-pursuit movements. The phenome- non was isolated to the right eye and subjectively was most obvious in areas of bright illumination. Following a rapid eye movement, the visual illusion consisted of three to five os- cillations of the viewed fixed object. A colleague noted iridodonesis that corresponded perfectly with the visual phe- nomena. Lens subluxation was diagnosed and treatment con- sisted of lens extraction and implantation.

To our knowledge the complaint of oscillopsia has not

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previously been reported with lens dislocation and anatomi- cally represents the most anterior extent of a lesion now known to be associated with this phenomenon. Oscillopsia may occur in many disorders that produce dysfunction of the brainstem, cerebrum, oculomotor system, and the peripheral and central connections of the vestibular system 11, 21. In our patient, it appears the phenomenon was optical in origin and was produced by an oscillating refractive error secondary to an unstable lens. One may draw an analogy to Bender’s “retinal nystagmus” [ 1) in naming this “lens nystagmus.”

The Department of Neurology Veterans Administration Hospital Salt Lake City, Utah

References 1. Bender MB: Oscillopsia. Arch Neurol 13:204-213, 1965 2. k igh JR, Zee DS: The neurology of eye movement. The Con-

temporary Neurology Series. Philadelphia, Davis, 1983

Multiple Sclerosis in Italy Milton Alter, MD, PhD, Eugene Sobel, PhD, Zoreh Davanipour, DVM, PhD, Gary Friday, MD, and Gerald Schartz, DO

Before accepting the conclusions of Granieri and colleagues [l] that Italy is a high-risk zone for multiple sclerosis (MS), we should consider the alternative that 46.1 per 100,000 population in 1981 is not a high value. In fact, it is low compared with the rates in more northerly areas reported recently after equally intensive investigations. These rates approach 100 cases per 100,000 in Scotland, Finland, and Scandinavia. Are we witnessing an “inflation” in the values of prevalence rates similar to the inflation affecting the value of currency? Compared with more northerly communities, the rates in Italy remain intermediate to low.

Neuroepidemioiogy Section Temple University School of Medicine Philadelphia, Pennsylvania 191 40

Reference 1. Granieri E, Tola R, Paolina E, et al: The frequency of multiple

sclerosis in Italy: a descriptive study in Ferrara. Ann Neurol 17180-84, 1985

Reply Enrico Granieri, MD, Rosaria Tola, MD, Ezio Paolino, MD, Giulio Rosati. MD,+ Mirko Carreras, MD, and V. Cinzia Monetti, M D

The objections of Alter et a1 to our suggestion rhar Italy may be a high-risk zone for multiple sclerosis (MS) require com- ment. We do not want to inflate prevalence rates of multiple sclerosis (MS), or force the entrance of Italy into the high- risk areas, as if it were an award to be sought. The question is different. Through our studies of the past ten years and

more, we want to underline that MS prevalence in our coun- try, at least in the past twenty years, is higher than was believed, reaching frequencies of the same order of mag- nitude as have been reported in other studies in Europe. This has important implications for the planning of research o n both the etiology and pathogenesis of MS and for health and social planning.

Neurological Clinic of the University of Ferrard Ferrara *Neurological Clinic of the University of Sajsari Sassari, Italy

Genetic Transmission of Myoclonus Epilepsy with Ragged Red Fibers Joseph Roger, M D

I was interested in the articles by Rosing et a1 { S ] and Di- Mauro et al [ l} concerning mitochondrial myopathies. They suggest that the mode of inheritance of some mitochondrial encephalomyopathies, particularly in the myoclonus epilepsy with ragged red fibers (MERRF; { 3 ) ) , is similar to transmis- sion of Leber’s disease (maternal heredity).

We have published f4 j the description of a case of slowly progressive myoclonic epilepsy with action myoclonus and a cerebellar syndrome similar to that observed in dyssynergia cerebellaris myoclonica, in which muscle biopsy showed the presence of a mitochondrial myopathy with ragged red fibers. Fukuhara, in a recent review concerning the syndrome he described (31, allows that our case is typical of MERRF. Our patient, a young male with negative family history, also has typical Leber’s disease.

I think that this observation, unknown by the authors, confirms their argumenrs.

Centre Saint Paul 300 Boulevard de Sainte-Marguerite 13009 Marseille. France

References DiMauro S , Bonilla E, Zeviani M, Nakagawa M, De Vivo DC: Mitochondrid myopathies. Ann Neurol 17:521-538, 1985 Fukuhara N: Myoclonus epilepsy and mitochondrial myopathy. In Scarlato G, Cerri C (eds): Mitochondria1 Pathology in Muscle Diseases. Padova, Piccin, 1983, pp 88-1 10 Fukuhara N, Tokiguchi S, Shirakawa S, Tsubaki T: Myoclonus epilepsy associated wirh ragged red fibers (mitochondrial abnor- malities): disease entity or syndrome! Light and electron micro- scopic studies of two cases and review of the literature. J Neurol Sci 47:117-133, 1980 Roger J, Pellissier JF, Dravet C, et d: DCg6nCresccnce spino- c6rebelleuse. Atrophie optique. Epilepsie-myoclonies. Myopa- thie mirochondriale. Rev Neurol 138: 187-200, 1982 Rosing HS, Hopkins LC, Wallace DL, et al: Maternally inherited mitochondrial myopathy and rnyoclonic epilepsy. Ann Neurol 17:228-237, 1985

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