1110
evidence of compression. Nerve conduction studies showed that compound muscle action potentials were much lower than on the previous admission. Electromyography and muscle biopsy results suggested the presence of neuropathic changes, and he was diagnosed as having ALS. During hospitalisation the muscular weakness began to improve. We learned that he had been treated with gangliosides and therefore sought antibodies against these agents. Thin-layer chromatography (TLC) with immunostaining showed that serum IgM reacted strongly with GM2, but did not react with GMl, GDIa, GDlb3 GTlb, GM2, GA2, GD2, and GM3. TLC showed that injected bovine brain gangliosides contained GM2 (NeuAc) as a minor component. Enzyme-linked irnmunosorbent assayZ revealed that his serum contained a high titre (> 32 000’) of IgM antibody against GM2 ganglioside, while antibody titres of sera from control subjects (n=14), patients with ALS (15), and patients with diabetic neuropathy who had received treatment with gangliosides (3) were all less than 128. A decrease in GM2 antibody titre was associated with clinical improvement without corticosteroids or After immunosuppressive drug treatment. receiving plasmapheresis in October he was able to walk for a short distance without a cane. Although no side-effects of ganglioside treatment other than discomfort at the injection site have been reportedinoculation of rabbits with gangliosides does cause an encephalomyelitis-like disorder in some cases.’ Moreover, there have been several reports of motoneuron-disease5,6 and Guillain-Barre syndrome2 associated with autoantibodies against gangliosides. A ganglioside mixture containing GM2 or other minor components with the same terminal sugar configuration may have been an immunogen that induced the motoneuron-disease-like disorder in our patient. These findings suggest that both ganglioside and ganglioside antibody treatment can lead to adverse reactions that resemble motoneuron disease or Guillain-Barre syndrome. in part by grants-in-aid from the Ministry of Education, Science, and Culture of Japan and the Ministry of Health and Welfare of Japan. We thank Dr Yoshio Hirabayashi (Shizuoka University) for valuable advice and providing authentic samples of gangliosides.
Supported
Department of Neurology,
NOBUHIRO YUKI SHUZO SATO TADASHI MIYATAKE
Brain Research Institute,
Nugata University, Nugata, 951 Japan
KAZUHIKO SUGIYAMA Third
of Internal Medicine,
Department Yamagata University
TADASHI KATAGIRI HIDEO SASAKI
Bradley WG. Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. Muscle Nerve 1990; 13: 833-42. 2. Yuki N, Yoshino H, Sato S, et al. Acute axonal polyneuropathy associated with anti-GM1, antibodies following Campylobacter enteritis. Neurology 1990; 40: 1.
1900-02. 3. Horowitz SH Therapeutic strategies in promiting penpheral nerve regeneration. Muscle Nerve 1989; 12: 314-22. 4. Nagai Y, Momoi T, Saito M, et al Ganghoside syndrome, a new autoimmune neurologic disorder, experimentally induced with brain gangliosides. Neurosci Lett 1976; 2: 107-11. 5. Freddo L, Yu RK, Latov N, et al Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease. Neurology 1986; 36: 454-58. 6 Pestronk A, Cornblath DR, Ilyas AA, et al. A treatable multifocal motor neuropathy with antibodies to GM, ganghoside. Ann Neurol 1988, 24: 73-78.
Axillary node micrometastases and breast cancer
SIR,—The International (Ludwig) Breast Cancer Study Groupl reported its results pertaining to the importance of detecting axillary node micrometastases_in 921 breast cancer subjects initially thought to have axillary-node-negative disease. Re-examination of the nodes following serial sectioning showed that 83 (9%) subjects had nodal micrometastases. These patients had a poorer disease-free (p = 0-003) and overall ’(p = 0.002) survival after 5 years’ median follow-up than those in whom no micrometastases were found. Since there is still
disagreement about the clinical usefulness of
detecting such micrometastases, we thirik it important to present the
DISEASE-FREE (DFS) AND OVERALL (OS) SURVIVAL OF PATIENTS WITH AXILLARY NODE MICROMETASTASES
+ ve = positive *Senal sectioned Fail=all recurrences second tumours) and all deaths irrespeatve of cause
(including
non-breast
6-year median follow-up results (table): survival is actuarial. The conclusions remain the
the results and their statistical conclusive. significance Consequently, the only remaining issue now is how such micrometastases can be detected without the tedium of serial sectioning. Our group is actively pursuing such a goal and hope to soon present its conclusions. same:
are even more
Ludwig Institute for Cancer Research, 8001 Zurich, Switzerland
A. M. NEVILLE
International Breast Cancer Study Group, Berne
K. N. PRICE R. D. GELBER A. GOLDHIRSCH
1. Bettelheim Neville
R, Price KN, Gelber RD, Davis BW, Castiglione M, Goldhirsch A, AM, International (Ludwig) Breast Cancer Study Group Prognostic importance of occult axillary lymph node micrometastases from breast cancers Lancet 1990; 335: 1565-68.
Lymphoscintigraphy with 1231-labelled epidermal growth factor SIR,-Dr Schatten and colleagues (Feb 16, p 395) suggest a high accuracy for their 1231-EGF scan. The scan of the abdomen which is shown (case 13, lower) appears to be mislabelled. The scan seems to show a hydronephrotic left kidney and dilated ureter (labelled "t") and a more normal right kidney labelled "n"; this finding would not be unreasonable in this patient who has enlarged pelvic nodes. The activity seen in the pelvis appears to be the bladder with slightly higher activity on the right than the left. lz3I-EGF or the 1231 -component is excreted largely in the urine’ and could result in the above appearances. Did this patient have a hydronephrotic left kidney and has the scan been mislabelled?
M. J. O’DOHERTY T. O. NUNAN A. J. COAKLEY
Department of Nuclear Medicine, St Thomas’ Hospital, London SE1 7EH, UK
1. Kalofonos HP, Pawhkowska T, Hemmingway A, et al. Antibody guided diagnosis and
therapy of brain gliomas using radiolabelled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase J Nucl Med 1989; 30: 1636-45.
***This letter has been shown follows.-ED. L.
to
Dr
Schatten, whose reply
SIR,—Iconfirm that our patient (case 13) had a hydronephrotic left kidney and dilated ureter, and that this scan (lower) was mislabelled. The label "n" referred to the deposit of activity on the left lower edge of scan, which showed uptake of epidermal growth factor in normal lymph nodes; "t" referred to the activity on the right lower edge of scan corresponding to metastatic lymph nodes, as confirmed by biopsy. All patients were catheterised to reduce activity in the bladder and to distinguish between uptake within the bladder and the uterus, which we evaluated by occluding the catheter and or flushing the bladder. We found an obvious difference-m distribution of activity in the pelvis; we judged the paramedian hot spot on the lower edge of scan to correspond with the priman
tumour. 1st Department of Obstetrics and Gynaecology, University of Vienna,
Vienna, Austria
C. SCHATTEN
evidence of compression. Nerve conduction studies showed that compound muscle action potentials were much lower than on the previous admission. Electromyography and muscle biopsy results suggested the presence of neuropathic changes, and he was diagnosed as having ALS. During hospitalisation the muscular weakness began to improve. We learned that he had been treated with gangliosides and therefore sought antibodies against these agents. Thin-layer chromatography (TLC) with immunostaining showed that serum IgM reacted strongly with GM2, but did not react with GMl, GDIa, GDlb3 GTlb, GM2, GA2, GD2, and GM3. TLC showed that injected bovine brain gangliosides contained GM2 (NeuAc) as a minor component. Enzyme-linked irnmunosorbent assayZ revealed that his serum contained a high titre (> 32 000’) of IgM antibody against GM2 ganglioside, while antibody titres of sera from control subjects (n=14), patients with ALS (15), and patients with diabetic neuropathy who had received treatment with gangliosides (3) were all less than 128. A decrease in GM2 antibody titre was associated with clinical improvement without corticosteroids or After immunosuppressive drug treatment. receiving plasmapheresis in October he was able to walk for a short distance without a cane. Although no side-effects of ganglioside treatment other than discomfort at the injection site have been reportedinoculation of rabbits with gangliosides does cause an encephalomyelitis-like disorder in some cases.’ Moreover, there have been several reports of motoneuron-disease5,6 and Guillain-Barre syndrome2 associated with autoantibodies against gangliosides. A ganglioside mixture containing GM2 or other minor components with the same terminal sugar configuration may have been an immunogen that induced the motoneuron-disease-like disorder in our patient. These findings suggest that both ganglioside and ganglioside antibody treatment can lead to adverse reactions that resemble motoneuron disease or Guillain-Barre syndrome. in part by grants-in-aid from the Ministry of Education, Science, and Culture of Japan and the Ministry of Health and Welfare of Japan. We thank Dr Yoshio Hirabayashi (Shizuoka University) for valuable advice and providing authentic samples of gangliosides.
Supported
Department of Neurology,
NOBUHIRO YUKI SHUZO SATO TADASHI MIYATAKE
Brain Research Institute,
Nugata University, Nugata, 951 Japan
KAZUHIKO SUGIYAMA Third
of Internal Medicine,
Department Yamagata University
TADASHI KATAGIRI HIDEO SASAKI
Bradley WG. Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. Muscle Nerve 1990; 13: 833-42. 2. Yuki N, Yoshino H, Sato S, et al. Acute axonal polyneuropathy associated with anti-GM1, antibodies following Campylobacter enteritis. Neurology 1990; 40: 1.
1900-02. 3. Horowitz SH Therapeutic strategies in promiting penpheral nerve regeneration. Muscle Nerve 1989; 12: 314-22. 4. Nagai Y, Momoi T, Saito M, et al Ganghoside syndrome, a new autoimmune neurologic disorder, experimentally induced with brain gangliosides. Neurosci Lett 1976; 2: 107-11. 5. Freddo L, Yu RK, Latov N, et al Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease. Neurology 1986; 36: 454-58. 6 Pestronk A, Cornblath DR, Ilyas AA, et al. A treatable multifocal motor neuropathy with antibodies to GM, ganghoside. Ann Neurol 1988, 24: 73-78.
Axillary node micrometastases and breast cancer
SIR,—The International (Ludwig) Breast Cancer Study Groupl reported its results pertaining to the importance of detecting axillary node micrometastases_in 921 breast cancer subjects initially thought to have axillary-node-negative disease. Re-examination of the nodes following serial sectioning showed that 83 (9%) subjects had nodal micrometastases. These patients had a poorer disease-free (p = 0-003) and overall ’(p = 0.002) survival after 5 years’ median follow-up than those in whom no micrometastases were found. Since there is still
disagreement about the clinical usefulness of
detecting such micrometastases, we thirik it important to present the
DISEASE-FREE (DFS) AND OVERALL (OS) SURVIVAL OF PATIENTS WITH AXILLARY NODE MICROMETASTASES
+ ve = positive *Senal sectioned Fail=all recurrences second tumours) and all deaths irrespeatve of cause
(including
non-breast
6-year median follow-up results (table): survival is actuarial. The conclusions remain the
the results and their statistical conclusive. significance Consequently, the only remaining issue now is how such micrometastases can be detected without the tedium of serial sectioning. Our group is actively pursuing such a goal and hope to soon present its conclusions. same:
are even more
Ludwig Institute for Cancer Research, 8001 Zurich, Switzerland
A. M. NEVILLE
International Breast Cancer Study Group, Berne
K. N. PRICE R. D. GELBER A. GOLDHIRSCH
1. Bettelheim Neville
R, Price KN, Gelber RD, Davis BW, Castiglione M, Goldhirsch A, AM, International (Ludwig) Breast Cancer Study Group Prognostic importance of occult axillary lymph node micrometastases from breast cancers Lancet 1990; 335: 1565-68.
Lymphoscintigraphy with 1231-labelled epidermal growth factor SIR,-Dr Schatten and colleagues (Feb 16, p 395) suggest a high accuracy for their 1231-EGF scan. The scan of the abdomen which is shown (case 13, lower) appears to be mislabelled. The scan seems to show a hydronephrotic left kidney and dilated ureter (labelled "t") and a more normal right kidney labelled "n"; this finding would not be unreasonable in this patient who has enlarged pelvic nodes. The activity seen in the pelvis appears to be the bladder with slightly higher activity on the right than the left. lz3I-EGF or the 1231 -component is excreted largely in the urine’ and could result in the above appearances. Did this patient have a hydronephrotic left kidney and has the scan been mislabelled?
M. J. O’DOHERTY T. O. NUNAN A. J. COAKLEY
Department of Nuclear Medicine, St Thomas’ Hospital, London SE1 7EH, UK
1. Kalofonos HP, Pawhkowska T, Hemmingway A, et al. Antibody guided diagnosis and
therapy of brain gliomas using radiolabelled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase J Nucl Med 1989; 30: 1636-45.
***This letter has been shown follows.-ED. L.
to
Dr
Schatten, whose reply
SIR,—Iconfirm that our patient (case 13) had a hydronephrotic left kidney and dilated ureter, and that this scan (lower) was mislabelled. The label "n" referred to the deposit of activity on the left lower edge of scan, which showed uptake of epidermal growth factor in normal lymph nodes; "t" referred to the activity on the right lower edge of scan corresponding to metastatic lymph nodes, as confirmed by biopsy. All patients were catheterised to reduce activity in the bladder and to distinguish between uptake within the bladder and the uterus, which we evaluated by occluding the catheter and or flushing the bladder. We found an obvious difference-m distribution of activity in the pelvis; we judged the paramedian hot spot on the lower edge of scan to correspond with the priman
tumour. 1st Department of Obstetrics and Gynaecology, University of Vienna,
Vienna, Austria
C. SCHATTEN
