751
nervous system other than those involving myelin; there is no myelin in the eye. It seems important to consider the possible role of
viruses in these manifestations. Since 1985 we have been looking for intraocular production of virus-specific antibodies by analysing the aqueous humour of patients with uveitisInflammation increases the amount of protein leaking from the blood to intraocular fluid, and to compare antibody concentrations in aqueous humour (AH) and in serum (S) we calculate, for each virus tested, C (the ocular synthesis of specific IgG) from the following formula:
(AH IgG/S IgG) - (AH albumin/S albumin) Two groups of patients were studied-13 with symptomatic uveitis associated with MS (group A), and 803 with idiopathic uveitis (group B). Uveitis was considered idiopathic after clinical evaluation and testing had eliminated known causes such as toxoplasmosis or diagnostic entities known to be associated with uveitis (eg, spondylarthritis, Reiter’s disease, Behçet’s syndrome, and sarcoidosis). Samples of blood and aqueous humour were assayed by enzyme-linked immunosorbent assay (’Enzygnost’; Behring) for IgGs specific for measles, herpes simplex, and varicella zoster virus and cytomegalovirus. Albumin was measured by laser nephelometry. Patients in group A had significantly increased ocular synthesis of antibodies to measles (but not to the other three viruses) when compared with group B: -
Male Mean age C value*
(SD)
Measles
Herpes simplex Varicella zoster
Cytomegalovirus
MS
(n = 13)
Idiopathic uveitis (n = 803)
31%
45%
39 (13) yr
37 (16) yr
69
(26, 208)t 35(14,43) 15(9,36) 36 (28,65)
19 (10, 41) 35(21,63) 12(6,21) 22 (11, 40)
*See text for definition; results as median (and 25th and 75th percentiles). tp 50% reduction 20%, (< 20% reduction in KCRS)
in
Kings College rating scale [KCRS]), KCRS), ----no response
reduction in
752
patients still have nausea, vomiting, postural hypotension, and drowsiness, so that a medical or nursing attendant is necessary
throughout the test. Although a shortened time-frame of the response to a specific dose of apomorphine might be judged an advantage, we feel that in all other respects an oral levodopa challenge test is a better test of dopaminergic responsiveness. The "gold standard", however, remains the chronic response to an adequate dose of levodopa. We therefore do not recommend the use of the apomorphine challenge test to determine dopaminergic responsiveness. Nevertheless, we do recognise the usefulness of apomorphine in treatment and as an acute measure to differentiate dopaminergic overstimulation from understimulation states (analagous to a Tensilon test). Finally, notwithstanding these findings, it is important to recognise that some patients with parkinsonism in whom both acute challenges and chronic levodopa treatment give apparently negative results may derive some useful benefit from chronic levodopa, which is appreciated only after such treatment has subsequently been withdrawn for several days. Therefore, in practice all parkinsonian patients should receive an adequate chronic trial of levodopa therapy whatever the results of their acute challenge tests. University Department of Clinical Neurology, Institute of Neurology, National Hospital, London WC1N 3BG, UK
M. J. STEIGER N. P. QUINN
Hughes AJ, Lees AJ, Stem GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990; 336: 32-34. 2. D’Costa DF, Abbott RJ, Pye IF, Millac PAH. The apomorphine test in parkinsonian syndromes. J Neurol Neurosurg Pyschiatry 1991; 54: 870-72. 3. Parkes JD, Zilkha KJ, Calver DM, Knill-Jones RP. Controlled trial of amantadine hydrochloride m Parkinson’s disease. Lancet 1970; i: 259-62. 4. Hughes AJ, Lees AJ, Stem GM. Challenge tests to predict the dopaminergic response m untreated Parkinson’s disease. Neurology 1991; 41: 1723-25. 1.
Transient selective C4 deficiency of
infancy
SIR,-We report a baby boy with selective C4 deficiency and recurrent erythema multiforme. This 9-week-old boy was admitted with fever and erythema multiforme. Urticaria was not seen. His birthweight was 2420 g at 37 weeks of gestation, and he grew well after birth. C4 concentrations (< 1 mg/dl) and CH50 (< 10 U/ml) were undetectable, with normal Clq, C2, C3, C5, C6, C7, C8, and C9 (6-6,2-2,58-2,16-5,4-3,5 7,8-3, and 7-3 mg/dl, respectively). C11 inactivator concentration (54 mg/dl) measured by an immunodiffusion assay was raised (normal 15-35 mg/dl). Serum IgM, IgG, and IgA values were normal. The patient was the second child of healthy parents, and serum concentrations of C3, C4, and CH50 were normal in his parents, elder sister, and paternal grandfather, and there was no family history of angioedema. Erythema multiforme gradually disappeared after 4 days without any treatment but reappeared with fever at 12 weeks of age, lasting for 7 days. In both episodes, raised C-reactive protein (CRP) values (4-7 mg/dl and 14-7 mg/dl) suggested the presence of bacterial or viral infections, and antibiotics were given for the second episode. The patient’s C4 and CH50 concentrations started to rise at age 17 weeks (20-6 mg/dl and 31-5 U/ml, respectively), and since then C4 and CH50 have remained normal. Erythema multiforme and susceptibility to viral and bacterial infections have not been seen since, now one year later. C3, C4, C5, and CH50 are detectable in fetal serum by the 18th week of gestation.1 Serum C3, C4, C5, and CH50 at birth are generally increased according to length of gestation, and are about 50-70% of normal adult values in full-term newborn babies. Concentrations then gradually increase until 6 months of age when they reach adult values.’ Selective deficiency of components of complement, including C4, has been reported; selective C4 deficiency can be seen in patients with systemic lupus erythematosus (SLE) and SLE-like disease,3and transient C4 deficiency sometimes arises in hereditary angioedema.1 However, as far as we are aware, primary transient selective C4 deficiency has not been reported previously. The mechanism of selective C4 deficiency in our patient is not clear. The patient’s transient C4 deficiency is unlikely to be secondary to consumption of complement by immune complexes,
because such a severe and selective consumption is not generally seen in erythema multiforme. Normal C3 and low C4 and CH50 values may accompany hereditary angioedema. However, C4 deficiency in hereditary angioedema is not usually as severe as in our case, and is often accompanied by a decrease of C2, which did not happen in our patient; nor were obvious angioedema attacks noted in him or his family. Moreover, Cl inactivator protein was raised, although its functional level was not determined. These data collectively suggest that the C4 deficiency in our patient was not the result but, rather, the cause of erythema multiforme; selective C4 deficiency may or may not induce susceptibility to infections, and viral and bacterial infections may cause erythema multiforme. The fever and raised CRP in our patient suggested the presence of infections in both episodes of erythema multiforme. Another possible factor in the transient selective C4 deficiency of infancy may be the transfer of inhibitory molecules from the mother. However, this is also unlikely, because C4 was normal in the mother. The low birthweight and early delivery of our patient might have caused immaturity of C4 synthesis. We suggest that primary transient selective C4 deficiency is a special form of immunodeficiency in infants, similar to transient hypogammaglobulinaemia of infancy.5 Such C4 deficiency of infancy has not been reported, probably because serum complement concentrations are less frequently examined in infants than is serum immunoglobulin. Department of Paediatrics, Kyoto University Hospital, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan
MITSUFUMI MAYUMI TOSHIO HEIKE HARUKI MIKAWA
DA, Taylor PM. Development of human complement system. J Immunol 1969; 103: 25-31. 2. Davis CA, Vallota EH, Forristal J. Serum complement levels in infancy: age related changes. Pediatr Res 1979; 13: 1043-46. 3. Hauptmann G, Goetz J, Uring-Lambert B, Grosshans E. C4 deficiency. In: Rother K, ed. Hereditary and acquired complement deficiencies. Progr Allergy 1986; 39: 1. Fireman P, Zuchowski
232-49.
Laurell, A-B. Complement determinations in clinical diagnosis. In: Rother K, Till GO, eds. The complement system. Berlin: Springer-Verlag, 1988: 272-87. 5. Rosen FS, Cooper MD, Wedgwood RJP. The primary immunodeficiencies. N Engl J Med 1984; 311: 300-10.
4.
Gardener’s mydriasis SiR,—To the many known causes of unilateral mydriasisl we would like to add gardening--a rare cause, perhaps, but awareness of the possibility could avoid unnecessary diagnostic tests. We sawa 54-year-old man who complained of blurred vision of sudden onset in his right eye while lifting a heavy flowerpot. There was no drug history. Examination was normal except for internal ophthalmoplegia of the right eye. The mydriasis disappeared over 48 hours. On detailed questioning he told us that he had been cutting "angel’s trumpet" (Datura suaveolens), a member of the nightshade family containing norscopolamine and scopolamine (hyoscine) as major, and atropine and noratropine as minor, constituents.2 Hyoscine produces mydriasis and cycloplegia of rapid onset, lasting 4-6 days.3 This was readily reproduced by one of us who applied to one eye one drop of juice from the plant the gardener had cut. Mydriasis reached a peak after 15 min and slowly wore off over the the next 6 days. Specific questioning may reveal gardening as the cause of unilateral mydriasis if there is no history of the use of eye drops or scopolamine patches.4,5Thus, unnecessary diagnostic tests may be avoided. Department of Neurology, Klinikum Groshadern, University of Munich, 8000 Munich 70, Germany
RAYMOND VOLTZ REINHARD HOHLFELD MARGARETE LIEBLER
Botanische Staatssammlung, Munich
HANNES HERTEL
1. Roy FH. Ocular differential diagnosis. Philadelphia: Lea & Febiger, 1989: 369-74. 2. Hegnauer R. Chemotaxonomie der Pflanzen: vol VI. Stuttgart: Birkhäuser, 1973-788. 3. Morrison JD, Reilly J. The effects of 0·025% hyoscine hydrobromide eyedrops on visual function m man. Ophthal Physiol Opt 1989; 9: 41-45. 4. Rosen NB. Accidental mydriasis from scopolamine patches.J Am Optom Assoc 1986; 57: 541-42. 5. Rubin MM, Sadoff RS, Cozzi GM. Unilateral mydriasis caused by transdermal scopolamine. Oral Surg Oral Med Oral Pathol 1990; 70: 569-70.
nervous system other than those involving myelin; there is no myelin in the eye. It seems important to consider the possible role of
viruses in these manifestations. Since 1985 we have been looking for intraocular production of virus-specific antibodies by analysing the aqueous humour of patients with uveitisInflammation increases the amount of protein leaking from the blood to intraocular fluid, and to compare antibody concentrations in aqueous humour (AH) and in serum (S) we calculate, for each virus tested, C (the ocular synthesis of specific IgG) from the following formula:
(AH IgG/S IgG) - (AH albumin/S albumin) Two groups of patients were studied-13 with symptomatic uveitis associated with MS (group A), and 803 with idiopathic uveitis (group B). Uveitis was considered idiopathic after clinical evaluation and testing had eliminated known causes such as toxoplasmosis or diagnostic entities known to be associated with uveitis (eg, spondylarthritis, Reiter’s disease, Behçet’s syndrome, and sarcoidosis). Samples of blood and aqueous humour were assayed by enzyme-linked immunosorbent assay (’Enzygnost’; Behring) for IgGs specific for measles, herpes simplex, and varicella zoster virus and cytomegalovirus. Albumin was measured by laser nephelometry. Patients in group A had significantly increased ocular synthesis of antibodies to measles (but not to the other three viruses) when compared with group B: -
Male Mean age C value*
(SD)
Measles
Herpes simplex Varicella zoster
Cytomegalovirus
MS
(n = 13)
Idiopathic uveitis (n = 803)
31%
45%
39 (13) yr
37 (16) yr
69
(26, 208)t 35(14,43) 15(9,36) 36 (28,65)
19 (10, 41) 35(21,63) 12(6,21) 22 (11, 40)
*See text for definition; results as median (and 25th and 75th percentiles). tp 50% reduction 20%, (< 20% reduction in KCRS)
in
Kings College rating scale [KCRS]), KCRS), ----no response
reduction in
752
patients still have nausea, vomiting, postural hypotension, and drowsiness, so that a medical or nursing attendant is necessary
throughout the test. Although a shortened time-frame of the response to a specific dose of apomorphine might be judged an advantage, we feel that in all other respects an oral levodopa challenge test is a better test of dopaminergic responsiveness. The "gold standard", however, remains the chronic response to an adequate dose of levodopa. We therefore do not recommend the use of the apomorphine challenge test to determine dopaminergic responsiveness. Nevertheless, we do recognise the usefulness of apomorphine in treatment and as an acute measure to differentiate dopaminergic overstimulation from understimulation states (analagous to a Tensilon test). Finally, notwithstanding these findings, it is important to recognise that some patients with parkinsonism in whom both acute challenges and chronic levodopa treatment give apparently negative results may derive some useful benefit from chronic levodopa, which is appreciated only after such treatment has subsequently been withdrawn for several days. Therefore, in practice all parkinsonian patients should receive an adequate chronic trial of levodopa therapy whatever the results of their acute challenge tests. University Department of Clinical Neurology, Institute of Neurology, National Hospital, London WC1N 3BG, UK
M. J. STEIGER N. P. QUINN
Hughes AJ, Lees AJ, Stem GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990; 336: 32-34. 2. D’Costa DF, Abbott RJ, Pye IF, Millac PAH. The apomorphine test in parkinsonian syndromes. J Neurol Neurosurg Pyschiatry 1991; 54: 870-72. 3. Parkes JD, Zilkha KJ, Calver DM, Knill-Jones RP. Controlled trial of amantadine hydrochloride m Parkinson’s disease. Lancet 1970; i: 259-62. 4. Hughes AJ, Lees AJ, Stem GM. Challenge tests to predict the dopaminergic response m untreated Parkinson’s disease. Neurology 1991; 41: 1723-25. 1.
Transient selective C4 deficiency of
infancy
SIR,-We report a baby boy with selective C4 deficiency and recurrent erythema multiforme. This 9-week-old boy was admitted with fever and erythema multiforme. Urticaria was not seen. His birthweight was 2420 g at 37 weeks of gestation, and he grew well after birth. C4 concentrations (< 1 mg/dl) and CH50 (< 10 U/ml) were undetectable, with normal Clq, C2, C3, C5, C6, C7, C8, and C9 (6-6,2-2,58-2,16-5,4-3,5 7,8-3, and 7-3 mg/dl, respectively). C11 inactivator concentration (54 mg/dl) measured by an immunodiffusion assay was raised (normal 15-35 mg/dl). Serum IgM, IgG, and IgA values were normal. The patient was the second child of healthy parents, and serum concentrations of C3, C4, and CH50 were normal in his parents, elder sister, and paternal grandfather, and there was no family history of angioedema. Erythema multiforme gradually disappeared after 4 days without any treatment but reappeared with fever at 12 weeks of age, lasting for 7 days. In both episodes, raised C-reactive protein (CRP) values (4-7 mg/dl and 14-7 mg/dl) suggested the presence of bacterial or viral infections, and antibiotics were given for the second episode. The patient’s C4 and CH50 concentrations started to rise at age 17 weeks (20-6 mg/dl and 31-5 U/ml, respectively), and since then C4 and CH50 have remained normal. Erythema multiforme and susceptibility to viral and bacterial infections have not been seen since, now one year later. C3, C4, C5, and CH50 are detectable in fetal serum by the 18th week of gestation.1 Serum C3, C4, C5, and CH50 at birth are generally increased according to length of gestation, and are about 50-70% of normal adult values in full-term newborn babies. Concentrations then gradually increase until 6 months of age when they reach adult values.’ Selective deficiency of components of complement, including C4, has been reported; selective C4 deficiency can be seen in patients with systemic lupus erythematosus (SLE) and SLE-like disease,3and transient C4 deficiency sometimes arises in hereditary angioedema.1 However, as far as we are aware, primary transient selective C4 deficiency has not been reported previously. The mechanism of selective C4 deficiency in our patient is not clear. The patient’s transient C4 deficiency is unlikely to be secondary to consumption of complement by immune complexes,
because such a severe and selective consumption is not generally seen in erythema multiforme. Normal C3 and low C4 and CH50 values may accompany hereditary angioedema. However, C4 deficiency in hereditary angioedema is not usually as severe as in our case, and is often accompanied by a decrease of C2, which did not happen in our patient; nor were obvious angioedema attacks noted in him or his family. Moreover, Cl inactivator protein was raised, although its functional level was not determined. These data collectively suggest that the C4 deficiency in our patient was not the result but, rather, the cause of erythema multiforme; selective C4 deficiency may or may not induce susceptibility to infections, and viral and bacterial infections may cause erythema multiforme. The fever and raised CRP in our patient suggested the presence of infections in both episodes of erythema multiforme. Another possible factor in the transient selective C4 deficiency of infancy may be the transfer of inhibitory molecules from the mother. However, this is also unlikely, because C4 was normal in the mother. The low birthweight and early delivery of our patient might have caused immaturity of C4 synthesis. We suggest that primary transient selective C4 deficiency is a special form of immunodeficiency in infants, similar to transient hypogammaglobulinaemia of infancy.5 Such C4 deficiency of infancy has not been reported, probably because serum complement concentrations are less frequently examined in infants than is serum immunoglobulin. Department of Paediatrics, Kyoto University Hospital, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan
MITSUFUMI MAYUMI TOSHIO HEIKE HARUKI MIKAWA
DA, Taylor PM. Development of human complement system. J Immunol 1969; 103: 25-31. 2. Davis CA, Vallota EH, Forristal J. Serum complement levels in infancy: age related changes. Pediatr Res 1979; 13: 1043-46. 3. Hauptmann G, Goetz J, Uring-Lambert B, Grosshans E. C4 deficiency. In: Rother K, ed. Hereditary and acquired complement deficiencies. Progr Allergy 1986; 39: 1. Fireman P, Zuchowski
232-49.
Laurell, A-B. Complement determinations in clinical diagnosis. In: Rother K, Till GO, eds. The complement system. Berlin: Springer-Verlag, 1988: 272-87. 5. Rosen FS, Cooper MD, Wedgwood RJP. The primary immunodeficiencies. N Engl J Med 1984; 311: 300-10.
4.
Gardener’s mydriasis SiR,—To the many known causes of unilateral mydriasisl we would like to add gardening--a rare cause, perhaps, but awareness of the possibility could avoid unnecessary diagnostic tests. We sawa 54-year-old man who complained of blurred vision of sudden onset in his right eye while lifting a heavy flowerpot. There was no drug history. Examination was normal except for internal ophthalmoplegia of the right eye. The mydriasis disappeared over 48 hours. On detailed questioning he told us that he had been cutting "angel’s trumpet" (Datura suaveolens), a member of the nightshade family containing norscopolamine and scopolamine (hyoscine) as major, and atropine and noratropine as minor, constituents.2 Hyoscine produces mydriasis and cycloplegia of rapid onset, lasting 4-6 days.3 This was readily reproduced by one of us who applied to one eye one drop of juice from the plant the gardener had cut. Mydriasis reached a peak after 15 min and slowly wore off over the the next 6 days. Specific questioning may reveal gardening as the cause of unilateral mydriasis if there is no history of the use of eye drops or scopolamine patches.4,5Thus, unnecessary diagnostic tests may be avoided. Department of Neurology, Klinikum Groshadern, University of Munich, 8000 Munich 70, Germany
RAYMOND VOLTZ REINHARD HOHLFELD MARGARETE LIEBLER
Botanische Staatssammlung, Munich
HANNES HERTEL
1. Roy FH. Ocular differential diagnosis. Philadelphia: Lea & Febiger, 1989: 369-74. 2. Hegnauer R. Chemotaxonomie der Pflanzen: vol VI. Stuttgart: Birkhäuser, 1973-788. 3. Morrison JD, Reilly J. The effects of 0·025% hyoscine hydrobromide eyedrops on visual function m man. Ophthal Physiol Opt 1989; 9: 41-45. 4. Rosen NB. Accidental mydriasis from scopolamine patches.J Am Optom Assoc 1986; 57: 541-42. 5. Rubin MM, Sadoff RS, Cozzi GM. Unilateral mydriasis caused by transdermal scopolamine. Oral Surg Oral Med Oral Pathol 1990; 70: 569-70.
