- Email: [email protected]
REINFECTION WITH BORRELIA BURGDORFERI
984
Pulsed
doppler scans in baby with gas bubbles in cerebral arteries.
A (left): duplex scan showing cursor in anterior cerebral artery above doppler sonogram demonstrating continuous forward blood flow throughout cardiac cycle.
B
(right): air bubbles (arrowed) in anterior cerebral artery. Doppler (due to bubbles) with no demonstrable blood flow.
sonogram reveals artifacts
’
When blood was subsequently aspirated from the arterial catheter it contained 5 ml gas (this finding has been noted by othersl-3). The infant died shortly afterwards. No gas was found post mortem. The formation of an alveolar-capillary fistula may result in the entry of air into the pulmonary veins.2 The absence of air post mortem has been previously noted3 and is thought to be due to rapid absorption of the oxygen. This is the first occasion that cerebral air embolus secondary to interstitial emphysema has been detected by pulsed doppler. The association may be more common than has hitherto been appreciated on clinical grounds or at post mortem. Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XW
J. GRANT J. F. MURPHY
Kogutt MS. Systemic air embolism secondary to respiratory therapy in the neonate: six cases including one survivor. Am J Roentgenol 1978; 131: 425-29. 2. Brown ZA, Clark JM, Jung AL. Systemic gas embolus. Am J Dis Child 1977; 131: 1.
984-85. 3. Rudd PT,
Wigglesworth JS. Oxygen embolus during mechanical ventilation disappearance of signs after death. Arch Dis Child 1982; 57: 237-39.
with
REINFECTION WITH BORRELIA BURGDORFERI
Serum
antibody titres against B burgdorferi.
Titres measured by indirect immunofluorescence after absorption with Treponema phagedenis; titres of 64 or more are considered positive.’ E.m. erythema migrans. =
SIR,-Lyme borreliosis, a tick-bome multisystem disorder caused by the spirochaete Borrelia burgdorferi, typically begins with erythema chronicum migrans and is sometimes followed by involvement of the heart, joints, and nervous system.’ Neurological manifestations include meningoradiculitis (Bannwarth’s syndrome), meningitis, and encephalitis.2-4 The clinical diagnosis can be confirmed by finding antibodies to B burgdorferi by indirect immunofluorescence or ELISA.5,6 We describe here a serologically and bacteriologically confirmed case of possible reinfection. In September, 1983, 2 weeks after a tick bite on the right arm, a 59-year-old woman had erythema migrans around the bite site. She presented on Nov 15 with a painful meningoradiculitis and bilateral papilloedema. CSF analysis showed a lymphocytic pleocytosis (330 cells/[tl) and an increase in total protein (82 mg/dl). Her serum IgG antibody titre against B burgdorferi rose from less than 16 to 256 within 4 weeks (figure). IgM antibodies were not detected, and borreliae could not be isolated from the CSF. The patient was treated with intravenous penicillin (20 megaunits daily for 5 days, then 10 megaunits daily for 5 days) and oral methylprednisolone (70 mg daily over 2 weeks with decreasing dosage). On discharge (Dec 12) she was free of pain, with a slightly improved vision.
Follow-up examinations showed residual bilateral papillatrophy. In October, 1984, the CSF was normal (1 cell/1, total protein 37
mg/dl).
On Oct 2, 1985, the patient visited a forest. She did not recall any arthropod bites but on Oct 5 a painful redness developed on the right side of her chest. She presented on Oct 7 with an erythema chronicum migrans, about 20 x 14 crn. Spirochaetes were isolated at biopsy of the skin around the lesion after 4 weeks’ incubation in modified Kelly’s medium. Her serum IgG antibody titre against B burgdorferi had been 16 on June 27, 1985 but had risen to 64 on Oct 17 without a corresponding IgM increase. Treatment with minocycline 200 mg daily by mouth for 14 days was successful. In 1958 Hollström reported a case of recurrent erythema migrans 5 years after primary infection.7 Skoldenberg et al in 1983 described a patient with two episodes, 20 years apart, of erythema migrans and meningitis after a tick bite.8 Serological tests were not done on these patients. In Weber and colleagues’ two patients with erythema migrans and reinfection after 5 and 7 years antibody titres against B burgdorferi did not increase.9
985
patient had Lyme borreliosis with Bannwarth’s Her serum IgG titre against B burgdorferi became negative within 10 months. Erythema chronicum migrans recurred 2 years later. The absence of IgM antibodies in acute manifestations of Lyme borreliosis has been described before.s,6 The 1985 episode presented after the patient had stayed for a long time in a forest in an area known to be endemic for B burgdorferi infection. Despite the absence of a known tick bite we think that the second attack was a reinfection and not a recurrence. The skin sites involved were different in the two episodes. Patients with Bannwarth’s syndrome usually retain a significant IgG titre against B burgdorferi for several years.s Our patient’s antibody titre was insignificant by 10 months. The antibiotic and/or corticosteroid treatment given for that first attack may explain the short-lived immunity, permitting reinfection after only 2 years. In 1983
our
syndrome.
Departments of Neurology and Dermatology, University of Munich, Klinikum Grosshadern, 8000 Munich 70, West Germany; and Max von Pettenkofer Institute for Hygiene and Medical Microbiology, University of Munich
HANS-WALTER PFISTER UWE NEUBERT BETTINA WILSKE VERA PREAC-MURSIC KARL MAX EINHÄUPL GIAN DOMENICO BORASIO
1. Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983; 308: 733-42. 2 Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: Meningitis, cranial neuritis and radiculoneuritis. Neurology 1985; 35: 47-53 3. Pfister H-W, Einhaupl KM, Preac-Mursic V, Wilske B, Schierz G. The spirochetal etiology of lymphocytic meningoradiculitis of Bannwarth (Bannwarth’s syndrome). J Neurol 1984; 231: 141-44. 4. Pfister H-W, Einhaupl KM, Preac-Mursic V, Wilske B. Similarity of neurological manifestations of Borrelia burgdorfen infections in America and Europe. Neurology 1985; 35: 1393-94. 5. Ackermann R, Kabatzki J, Boisten HP, et al. Spirochaten—Ätiologie der Erythema chronicum migrans. Krankheit Dtsch Med Wschr 1984; 109: 92-97. 6. Wilske B, Schierz G, Preac-Mursic V, Weber K, Pfister HW, Einhaupl KM. Serological diagnosis of erythema migrans disease and related disorders. Infection 1984; 12: 331-37. 7. Hollström E. Penicillin treatment of erythema chronicum migrans Afzelius. Acta Derm-Vener 1958; 38: 285-89. 8. Sköldenberg B, Stiernstedt G, Garde A, Kolmodin G, Carlstrom A, Nord CE. Chronic meningitis caused by a penicillin-sensitive microorganism? Lancet 1983; ii: 75-78. 9. Weber K, Schierz G, Wilske B, et al. Reinfection in erythema migrans disease. Infection 1986; 14: 32-35.
DIFFERENTIAL DIAGNOSIS OF MOTONEURONE DISEASE FROM OTHER NEUROLOGICAL CONDITIONS
SIR,-We read with interest Mr Li and his colleagues’ clinical algorithm (Sept 27, p 731). Using four steps they have achieved 98% sensitivity and 86% specificity in distinguishing previously diagnosed motoneurone disease (MND) from three other previously diagnosed conditions-namely, stroke, multiple sclerosis, and cervical spondylosis with myelopathy. The algorithm is suggested for use as a baseline diagnostic criterion, especially in ‘
clinical research into MND. However, as stated in the paper, it is in general practice not clinical research where these three conditions cause the greatest diagnostic confusion. The annual incidence of MND is 1 per 100 000/ the average general practitioner is likely to see one new case every forty years, and the algorithm would seem irrelevant to him. More importantly there are disorders not considered in the algorithm which can produce clinical syndromes identical to MND. Hypophosphataemia2 from various causes, primary3 and secondary’ hyperparathyroidism, hyperthyroidism,5 and heavy metal poisoning (mercurY’ and lead7) can all present with muscle fasciculation, wasting, and, in some instances, hyperactive deep tendon reflexes without sensory loss. It is these four clinical signs which comprise the suggested algorithm. Therefore if it were used indiscriminately without knowledge of the wider differential diagnosis potentially treatable disorders could be overlooked. All suspected cases of MND should be referred to a neurologist, who will screen for metabolic disorders and carry out neurophysiological investigations before arriving at a diagnosis. Here the algorithm does not add to established clinical practice.
In MND research
accurate
diagnosis
is fundamental. This
requires selection of only those patients who have been fully investigated, not simply those labelled clinically as having MND. Applying a purely clinical algorithm is inappropriate and it has no place in the selection process. The only valid application of this algorithm would seem to be in demonstrating that patients already diagnosed as having MND, and displaying all four of the clinical signs listed above, are highly unlikely to have multiple sclerosis, a stroke, or cervical spondylosis with myelopathy. Why and when this information will be useful is not clear. Therefore we feel that this algorithm is of little practical value and that if it were used it would be potentially misleading. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF
I. K. HART I. BONE
1. Walton JN. Brain’s diseases of the nervous system, 8th ed. Oxford: Oxford
University Press, 1977: 685. 2. Mallette LE, Patten BM. Neurogenic muscular atrophy and osteomalacia in the adult Fancom syndrome. Ann Neurol 1977; 1: 131-37. 3. Patten BM, Bilezikan JP, Mallette LE, Prince A, Engel WK, Aurbach GR. Neuromuscular disease in primary hyperparathyroidism. Ann Intern Med 1974; 80: 182-93. 4. Mallette LE, Patten BM, Engel WK. Neuromuscular disease in secondary hyperparathyroidism. Ann Intern Med 1975; 82: 474-83. 5. Ramsay ID. Electromyography in thyrotoxicosis. Quart J Med 1965; 37: 255. 6. Felmus MT, Patten BM, Swanke LB. Antecedent events in amyotrophic lateral sclerosis. Neurology (Minneap) 1976; 26: 167. 7. Boothby JA, De Janus PU, Rowland LP. Reversible forms of MND: Lead neuritis. Arch Neurol (Chicago) 1974; 31: 18.
WHEN SHOULD LEVODOPA BE STARTED?
SiR,—The long-running debate over early versus late levodopa for Parkinson’s disease has lately resurfaced in your columns. We agree with Pincus1 that, despite theoretical reasons why chronic levodopa therapy might be harmful/.3 there is no conclusive evidence to support delaying levodopa treatment. However, we think that the best time to begin such therapy varies from patient to patient. Most of the evidence on early versus late levodopa treatment has come from analyses of disease progression, achieved by allotting point-in-time disability scores after various times on treatment.4,s However, such scores are difficult to apply once patients begin to fluctuate. Another way of examining the effect of chronic levodopa is to examine the prevalence of dyskinesias and fluctuations. The latency from onset of treatment to the development of these complications can then be correlated with, among other factors, the treatment
duration of disease before treatment. We have studied this in patients with idiopathic Parkinson’s disease (IPD) of early onset, in whom the problem of when to begin levodopa treatment is especially difficult. We have seen 56 patients with IPD beginning after their 21st and before their 40th birthday (median age of onset 35 years). 51 of these patients have received treatment with levodopa preparations. The prevalence of dyskinesias and fluctuations was very high, and was clearly related to the duration of levodopa treatment (table). Disease duration before levodopa therapy was compared with latency to PREVALENCE OF DYSKINESIAS AND FLUCTUATIONS IN RELATION TO DURATION OF LEVODOPA TREATMENT FOR PARKINSON’S DISEASE: CUMULATIVE PERCENTAGES AMONG YOUNG-ONSET PATIENTS
511
Pulsed
doppler scans in baby with gas bubbles in cerebral arteries.
A (left): duplex scan showing cursor in anterior cerebral artery above doppler sonogram demonstrating continuous forward blood flow throughout cardiac cycle.
B
(right): air bubbles (arrowed) in anterior cerebral artery. Doppler (due to bubbles) with no demonstrable blood flow.
sonogram reveals artifacts
’
When blood was subsequently aspirated from the arterial catheter it contained 5 ml gas (this finding has been noted by othersl-3). The infant died shortly afterwards. No gas was found post mortem. The formation of an alveolar-capillary fistula may result in the entry of air into the pulmonary veins.2 The absence of air post mortem has been previously noted3 and is thought to be due to rapid absorption of the oxygen. This is the first occasion that cerebral air embolus secondary to interstitial emphysema has been detected by pulsed doppler. The association may be more common than has hitherto been appreciated on clinical grounds or at post mortem. Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XW
J. GRANT J. F. MURPHY
Kogutt MS. Systemic air embolism secondary to respiratory therapy in the neonate: six cases including one survivor. Am J Roentgenol 1978; 131: 425-29. 2. Brown ZA, Clark JM, Jung AL. Systemic gas embolus. Am J Dis Child 1977; 131: 1.
984-85. 3. Rudd PT,
Wigglesworth JS. Oxygen embolus during mechanical ventilation disappearance of signs after death. Arch Dis Child 1982; 57: 237-39.
with
REINFECTION WITH BORRELIA BURGDORFERI
Serum
antibody titres against B burgdorferi.
Titres measured by indirect immunofluorescence after absorption with Treponema phagedenis; titres of 64 or more are considered positive.’ E.m. erythema migrans. =
SIR,-Lyme borreliosis, a tick-bome multisystem disorder caused by the spirochaete Borrelia burgdorferi, typically begins with erythema chronicum migrans and is sometimes followed by involvement of the heart, joints, and nervous system.’ Neurological manifestations include meningoradiculitis (Bannwarth’s syndrome), meningitis, and encephalitis.2-4 The clinical diagnosis can be confirmed by finding antibodies to B burgdorferi by indirect immunofluorescence or ELISA.5,6 We describe here a serologically and bacteriologically confirmed case of possible reinfection. In September, 1983, 2 weeks after a tick bite on the right arm, a 59-year-old woman had erythema migrans around the bite site. She presented on Nov 15 with a painful meningoradiculitis and bilateral papilloedema. CSF analysis showed a lymphocytic pleocytosis (330 cells/[tl) and an increase in total protein (82 mg/dl). Her serum IgG antibody titre against B burgdorferi rose from less than 16 to 256 within 4 weeks (figure). IgM antibodies were not detected, and borreliae could not be isolated from the CSF. The patient was treated with intravenous penicillin (20 megaunits daily for 5 days, then 10 megaunits daily for 5 days) and oral methylprednisolone (70 mg daily over 2 weeks with decreasing dosage). On discharge (Dec 12) she was free of pain, with a slightly improved vision.
Follow-up examinations showed residual bilateral papillatrophy. In October, 1984, the CSF was normal (1 cell/1, total protein 37
mg/dl).
On Oct 2, 1985, the patient visited a forest. She did not recall any arthropod bites but on Oct 5 a painful redness developed on the right side of her chest. She presented on Oct 7 with an erythema chronicum migrans, about 20 x 14 crn. Spirochaetes were isolated at biopsy of the skin around the lesion after 4 weeks’ incubation in modified Kelly’s medium. Her serum IgG antibody titre against B burgdorferi had been 16 on June 27, 1985 but had risen to 64 on Oct 17 without a corresponding IgM increase. Treatment with minocycline 200 mg daily by mouth for 14 days was successful. In 1958 Hollström reported a case of recurrent erythema migrans 5 years after primary infection.7 Skoldenberg et al in 1983 described a patient with two episodes, 20 years apart, of erythema migrans and meningitis after a tick bite.8 Serological tests were not done on these patients. In Weber and colleagues’ two patients with erythema migrans and reinfection after 5 and 7 years antibody titres against B burgdorferi did not increase.9
985
patient had Lyme borreliosis with Bannwarth’s Her serum IgG titre against B burgdorferi became negative within 10 months. Erythema chronicum migrans recurred 2 years later. The absence of IgM antibodies in acute manifestations of Lyme borreliosis has been described before.s,6 The 1985 episode presented after the patient had stayed for a long time in a forest in an area known to be endemic for B burgdorferi infection. Despite the absence of a known tick bite we think that the second attack was a reinfection and not a recurrence. The skin sites involved were different in the two episodes. Patients with Bannwarth’s syndrome usually retain a significant IgG titre against B burgdorferi for several years.s Our patient’s antibody titre was insignificant by 10 months. The antibiotic and/or corticosteroid treatment given for that first attack may explain the short-lived immunity, permitting reinfection after only 2 years. In 1983
our
syndrome.
Departments of Neurology and Dermatology, University of Munich, Klinikum Grosshadern, 8000 Munich 70, West Germany; and Max von Pettenkofer Institute for Hygiene and Medical Microbiology, University of Munich
HANS-WALTER PFISTER UWE NEUBERT BETTINA WILSKE VERA PREAC-MURSIC KARL MAX EINHÄUPL GIAN DOMENICO BORASIO
1. Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983; 308: 733-42. 2 Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: Meningitis, cranial neuritis and radiculoneuritis. Neurology 1985; 35: 47-53 3. Pfister H-W, Einhaupl KM, Preac-Mursic V, Wilske B, Schierz G. The spirochetal etiology of lymphocytic meningoradiculitis of Bannwarth (Bannwarth’s syndrome). J Neurol 1984; 231: 141-44. 4. Pfister H-W, Einhaupl KM, Preac-Mursic V, Wilske B. Similarity of neurological manifestations of Borrelia burgdorfen infections in America and Europe. Neurology 1985; 35: 1393-94. 5. Ackermann R, Kabatzki J, Boisten HP, et al. Spirochaten—Ätiologie der Erythema chronicum migrans. Krankheit Dtsch Med Wschr 1984; 109: 92-97. 6. Wilske B, Schierz G, Preac-Mursic V, Weber K, Pfister HW, Einhaupl KM. Serological diagnosis of erythema migrans disease and related disorders. Infection 1984; 12: 331-37. 7. Hollström E. Penicillin treatment of erythema chronicum migrans Afzelius. Acta Derm-Vener 1958; 38: 285-89. 8. Sköldenberg B, Stiernstedt G, Garde A, Kolmodin G, Carlstrom A, Nord CE. Chronic meningitis caused by a penicillin-sensitive microorganism? Lancet 1983; ii: 75-78. 9. Weber K, Schierz G, Wilske B, et al. Reinfection in erythema migrans disease. Infection 1986; 14: 32-35.
DIFFERENTIAL DIAGNOSIS OF MOTONEURONE DISEASE FROM OTHER NEUROLOGICAL CONDITIONS
SIR,-We read with interest Mr Li and his colleagues’ clinical algorithm (Sept 27, p 731). Using four steps they have achieved 98% sensitivity and 86% specificity in distinguishing previously diagnosed motoneurone disease (MND) from three other previously diagnosed conditions-namely, stroke, multiple sclerosis, and cervical spondylosis with myelopathy. The algorithm is suggested for use as a baseline diagnostic criterion, especially in ‘
clinical research into MND. However, as stated in the paper, it is in general practice not clinical research where these three conditions cause the greatest diagnostic confusion. The annual incidence of MND is 1 per 100 000/ the average general practitioner is likely to see one new case every forty years, and the algorithm would seem irrelevant to him. More importantly there are disorders not considered in the algorithm which can produce clinical syndromes identical to MND. Hypophosphataemia2 from various causes, primary3 and secondary’ hyperparathyroidism, hyperthyroidism,5 and heavy metal poisoning (mercurY’ and lead7) can all present with muscle fasciculation, wasting, and, in some instances, hyperactive deep tendon reflexes without sensory loss. It is these four clinical signs which comprise the suggested algorithm. Therefore if it were used indiscriminately without knowledge of the wider differential diagnosis potentially treatable disorders could be overlooked. All suspected cases of MND should be referred to a neurologist, who will screen for metabolic disorders and carry out neurophysiological investigations before arriving at a diagnosis. Here the algorithm does not add to established clinical practice.
In MND research
accurate
diagnosis
is fundamental. This
requires selection of only those patients who have been fully investigated, not simply those labelled clinically as having MND. Applying a purely clinical algorithm is inappropriate and it has no place in the selection process. The only valid application of this algorithm would seem to be in demonstrating that patients already diagnosed as having MND, and displaying all four of the clinical signs listed above, are highly unlikely to have multiple sclerosis, a stroke, or cervical spondylosis with myelopathy. Why and when this information will be useful is not clear. Therefore we feel that this algorithm is of little practical value and that if it were used it would be potentially misleading. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF
I. K. HART I. BONE
1. Walton JN. Brain’s diseases of the nervous system, 8th ed. Oxford: Oxford
University Press, 1977: 685. 2. Mallette LE, Patten BM. Neurogenic muscular atrophy and osteomalacia in the adult Fancom syndrome. Ann Neurol 1977; 1: 131-37. 3. Patten BM, Bilezikan JP, Mallette LE, Prince A, Engel WK, Aurbach GR. Neuromuscular disease in primary hyperparathyroidism. Ann Intern Med 1974; 80: 182-93. 4. Mallette LE, Patten BM, Engel WK. Neuromuscular disease in secondary hyperparathyroidism. Ann Intern Med 1975; 82: 474-83. 5. Ramsay ID. Electromyography in thyrotoxicosis. Quart J Med 1965; 37: 255. 6. Felmus MT, Patten BM, Swanke LB. Antecedent events in amyotrophic lateral sclerosis. Neurology (Minneap) 1976; 26: 167. 7. Boothby JA, De Janus PU, Rowland LP. Reversible forms of MND: Lead neuritis. Arch Neurol (Chicago) 1974; 31: 18.
WHEN SHOULD LEVODOPA BE STARTED?
SiR,—The long-running debate over early versus late levodopa for Parkinson’s disease has lately resurfaced in your columns. We agree with Pincus1 that, despite theoretical reasons why chronic levodopa therapy might be harmful/.3 there is no conclusive evidence to support delaying levodopa treatment. However, we think that the best time to begin such therapy varies from patient to patient. Most of the evidence on early versus late levodopa treatment has come from analyses of disease progression, achieved by allotting point-in-time disability scores after various times on treatment.4,s However, such scores are difficult to apply once patients begin to fluctuate. Another way of examining the effect of chronic levodopa is to examine the prevalence of dyskinesias and fluctuations. The latency from onset of treatment to the development of these complications can then be correlated with, among other factors, the treatment
duration of disease before treatment. We have studied this in patients with idiopathic Parkinson’s disease (IPD) of early onset, in whom the problem of when to begin levodopa treatment is especially difficult. We have seen 56 patients with IPD beginning after their 21st and before their 40th birthday (median age of onset 35 years). 51 of these patients have received treatment with levodopa preparations. The prevalence of dyskinesias and fluctuations was very high, and was clearly related to the duration of levodopa treatment (table). Disease duration before levodopa therapy was compared with latency to PREVALENCE OF DYSKINESIAS AND FLUCTUATIONS IN RELATION TO DURATION OF LEVODOPA TREATMENT FOR PARKINSON’S DISEASE: CUMULATIVE PERCENTAGES AMONG YOUNG-ONSET PATIENTS
511