Movement Disorders Val. 7, No. 2, 1992, pp. 178-180, 0 1992 Movement Disorder Society
VIDEO
SUPPLEHEW
Brief Report
Postvaccinal Parkinsonism Rosana S. C. Alves, Egberto R. Barbosa, and Milberto Scaff Department of Neurology, General Hospital, University of Slio Paulo Medical School, Slio Paulo, Brazil
Summary: A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear-cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features. Key Words: Encephalitis-Rigid-akinetic syndrome-Parkinsonism.
We describe the case of a child with postencephalitic parkinsonian features following the vaccination for measles. The magnetic resonance image (MRI) scan revealed bilateral lesions in substantia nigra.
hypomimia, sialorrhea, severe dysarthria, rigidity, and bradykinesia, mainly on the left side. Muscle tone was increased, also predominantly on the left side. By then, he was unable to walk (he did not assume the orthostatic position without help) and was totally dependent on help for feeding and hygiene. The child had no family history of movement disorders, and the parents were nonconsanguineous. A spinal tap obtained 1 month after the fever showed a normal pattern (1.7 cellslmm, protein 30 mgldl, negative stain, and a normal protein electrophoretic profile). Antibodies in the CSF against various viruses were not investigated. Metabolic studies ruled out Wilson's disease. A computed tomography (CT) brain scan and electroencephalogram (EEG) did not show any abnormality. MRI performed 3 months after the fever showed hyperintense signals in the substantia nigra, greater on the left side, and suggesting secondary gliosis (Fig. 1). Levodopa (125 mg/day) was prescribed, leading to a moderate improvement in the first 2 weeks. However, levodopa-induced dyskinesias (choreic movements) and motor performance fluctuations appeared. Biperidine 6 mg/day was without benefit. Two months later, bromocriptine was added, biperidine was reduced, and levodopa was raised to 250 mg/day. Six months later, a great relief of parkinsonism was obtained, levodopa was slowly reduced, and biperidine was discontinued. Dyskinesias diminished when levodopa was reduced to 125 mg/day. One year after the onset of the parkinsonism, deprenyl (10 mg/day) was added in an attempt to control motor performance fluctuations, with a good therapeutic response. The child is currently 7 years old. Rigidity is still
CASE REPORT At the age of 5 years, this boy developed fever 15 days after a subcutaneous injection of measles vaccine (prepared with live virus). The child had a prior history of vaccination (he had received the first dose at 9 months of age). Three days after the onset of fever (that lasted 4 days and was -39-4OoC), the child presented with a left hemiparesis accompanied by dysarthria and a generalized rigid-akinetic syndrome, predominantly on the left side. The tendon reflexes were normal, and the plantar reflex was flexor. One week after the onset of fever he had a tonic-clonic seizure beginning on the right side. There was no alteration of consciousness at any time of the disease. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern (20 cellslmm, 90% lymphocytes, 5% mononuclear, 3% plasma cells, 2% neutrophils), glucose 56 mg/dl, and protein 25 mg/dl; and negative stain and culture. One month later he was referred to our hospital with Videotape segments accompany the article. Address correspondence and reprint requests to Dr. R. S. C. Alves at Departamento de Neurologia, 5.0 andar, Hospital das Clinicas, Faculdade de Medicina, Universidade de SPo Paulo, Av. Dr. Eneas de Carvalho Aguiar s.n. 05403 SPo Paulo SP, Brazil.
178
179
POSTVACCINAL PARKINSONISM
FIG. 1. MRI shows hyperintense signals affecting the substantia nigra bilaterally, greater on the left side.
moderate and a mild bradykinesia is present on the left side, but there is little dysarthria and hypomimia. The patient is able to walk and run, as well as to eat and attend to personal hygiene. He can draw, and write some letters and numbers. He is currently receiving bromocriptine (25 mg/day), levodopa (125 mg/day), and deprenyl (10 mg/day). A 24-h interruption of levodopa resulted in a marked increase of the parkinsonism, indicating the persistence of the disorder.
DISCUSSION This child is an unusual case of postvaccinal parkinsonism, which began 2 weeks after the vaccination with attenuated live measles vaccine. The virus was cultured in chick embryo tissue; the viral strains were Muraten or Schwarz. The parkinsonism is still present 2 years after its onset. It appears that many viruses can produce parkinsonism (1). Encephalitis lethargica was the first type of epidemic encephalitis to be fully recognized, and for this reason both terms were considered synonymous. Thereafter, in addition to encephalitis lethargica (or type A), other viral encephalitides were found to induce parkinsonism, such as Japanese B encephalitis (2,3), St. Louis encephalitis (4), Eastern equine encephalitis (9,Western equine encephalitis (6), and even poliomyelitis (7). Parkinsonian features have likewise been noted in encephalitis due to measles and varicella, but such instances are relatively rare and all are transient (8,9). In the case described here, the child had fever, without any cutaneous abnormalities, 15 days after a vaccine shot for measles and then developed parkinsonism that has been present up to now, 2 years later. To the best of our knowledge, there is no report in the literature of postvaccinal parkinsonism. Hypomimia, rigidity, and distur-
bances of gait and posture in the acute phase of encephalitis due to measles, varicella, poliomyelitis, and arb0 viruses are usually transient. No more than 10 cases in the United States and Canada are considered to be parkinsonian-like residuals of viral encephalitis (1). There are also two reports of parkinsonism following infections of the nervous system by other viruses: one after herpes ophthalmicus (lo), and the other after a meningoencephalitis due to Coxsackie B Virus (1 1). Another report of postinfectious parkinsonism is one that followed “mild” influenza (12), although the features were transient. In encephalitis lethargica, a viral agent was never identified, though the clinical and pathological features were typical of viral infection. Lymphocytic pleocytosis in the cerebrospinal fluid occurred in over half of the patients (13), as also described in this report. The substantia nigra lesion alone in the case presently reported, as disclosed by MRI, is a unique finding, as it points to a perfect clinicalpathological relationship. The response to levodopa was good, but the appearance of the dyskinesias occurred at a low dosage. This is in agreement with the literature, inasmuch as postencephalitic patients respond better to levodopa, but the adverse reactions tend to occur at a lower dosage (14,15). The fair response to deprenyl in this case is another interesting aspect, as we have not found any report of encephalitic parkinsonism being treated with this drug. Acknowledgment: We are grateful to Drs. J. C. Papaterra Limongi, Luiz R. Comerlatti, Paulo Caramelli, Monica S . Haddad, and Cesar Timo-Iariafor their suggestions. Our special gratitude is hereby expressed to Dr. Stanley Fahn for encouragement to report the case.
LEGENDS TO VIDEOTAPE Segment 1. Day of admission to the hospital. Segment 2. Two years after the onset of disease, on levodopa therapy. Segment 3. Worsening of parkinsonism during a 24-h interruption of levodopa therapy.
REFERENCES 1 . Duvoisin RC, Yahr MD. Encephalitis and parkinsonism. Arch Neurol 1965;12:227-239. 2. Kaneko R. On epidemic encephalitis which occurred in Japan in 1924. Jpn Med World 1925;5:237-241. 3. Goto A. Follow-up study of Japanese B encephalitis. Psychiatr Neurol Jpn 1962;64:236-286. 4. Bredeck JF, et al. Follow-up studies of 1933 St. Louis Epidemic of Encephalitis. JAMA 1938;111:15-17. 5 . Chambers BA, Levey GS. Studies of Eastern encephalitis. Paper presented at the 13th Annual Meeting of the American Academy of Neurology, Detroit, 1961. 6. Adamson JD, Dubo S . Clinical findings in encephalitis (Western Equine). Can J Public Health 1942;32:288. 7. Warembourg H, et al. Syndrome Parkinsonien: SCquelle d’une poliomyelite aigne a forme d’encephalite 1’Cthargique chez un enfant de 20 mois. Sem Hop Paris 1962;38:22992307. 8. Kurland LT. Epidemiology: incidence, geographic distribution and genetic considerations. In: Fields WS, ed. Patho-
Movement Disorders, Vol. 7, N o . 2, 1992
R . S . C . ALVES E T A L .
9. 10.
11. 12.
genesis and treatment of Parkinsonism. Springfield: Charles Thomas Publisher, 1958. Meyer B. Encephalitis after measles with severe parkinsonian rigidity: recovery. Br Med J 1943;1:508. Strong G. Parkinson’s syndrome following severe herpes ophthalmicus. Br Med J 1952;1:533. Walters JH. Postencephalitic Parkinson syndrome after meningoencephalitis due to Coxsackie virus group B. N Engl J Med 1960;230:74&747. Isgreen WP, Chutorian AM, Fahn S. Sequential parkinson-
Movement Disorders, Vol. 7, No. 2, 1992
ism and chorea following “mild” influenza. Trans Am Neurol Assoc 1976;101:5&59. 13. Krusz JC, Koller WC, Ziegler DK. Historical review. Abnormal movements associated with epidemic encephalitis lethargica. Mov Disord 1987;2:137-141. 14. Duvoisin RC, Cabo-Antanes J, Yahr MD. The response of patients with postencephalitic parkinsonism to levodopa. J Neurol Neurosurg Psychiatr 1972;35:487-495. 15. Calne DB, Stern GM, Sharkey J. L-Dopa in postencephalitic parkinsonism. Lancet 1969;1:744-746.
VIDEO
SUPPLEHEW
Brief Report
Postvaccinal Parkinsonism Rosana S. C. Alves, Egberto R. Barbosa, and Milberto Scaff Department of Neurology, General Hospital, University of Slio Paulo Medical School, Slio Paulo, Brazil
Summary: A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear-cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features. Key Words: Encephalitis-Rigid-akinetic syndrome-Parkinsonism.
We describe the case of a child with postencephalitic parkinsonian features following the vaccination for measles. The magnetic resonance image (MRI) scan revealed bilateral lesions in substantia nigra.
hypomimia, sialorrhea, severe dysarthria, rigidity, and bradykinesia, mainly on the left side. Muscle tone was increased, also predominantly on the left side. By then, he was unable to walk (he did not assume the orthostatic position without help) and was totally dependent on help for feeding and hygiene. The child had no family history of movement disorders, and the parents were nonconsanguineous. A spinal tap obtained 1 month after the fever showed a normal pattern (1.7 cellslmm, protein 30 mgldl, negative stain, and a normal protein electrophoretic profile). Antibodies in the CSF against various viruses were not investigated. Metabolic studies ruled out Wilson's disease. A computed tomography (CT) brain scan and electroencephalogram (EEG) did not show any abnormality. MRI performed 3 months after the fever showed hyperintense signals in the substantia nigra, greater on the left side, and suggesting secondary gliosis (Fig. 1). Levodopa (125 mg/day) was prescribed, leading to a moderate improvement in the first 2 weeks. However, levodopa-induced dyskinesias (choreic movements) and motor performance fluctuations appeared. Biperidine 6 mg/day was without benefit. Two months later, bromocriptine was added, biperidine was reduced, and levodopa was raised to 250 mg/day. Six months later, a great relief of parkinsonism was obtained, levodopa was slowly reduced, and biperidine was discontinued. Dyskinesias diminished when levodopa was reduced to 125 mg/day. One year after the onset of the parkinsonism, deprenyl (10 mg/day) was added in an attempt to control motor performance fluctuations, with a good therapeutic response. The child is currently 7 years old. Rigidity is still
CASE REPORT At the age of 5 years, this boy developed fever 15 days after a subcutaneous injection of measles vaccine (prepared with live virus). The child had a prior history of vaccination (he had received the first dose at 9 months of age). Three days after the onset of fever (that lasted 4 days and was -39-4OoC), the child presented with a left hemiparesis accompanied by dysarthria and a generalized rigid-akinetic syndrome, predominantly on the left side. The tendon reflexes were normal, and the plantar reflex was flexor. One week after the onset of fever he had a tonic-clonic seizure beginning on the right side. There was no alteration of consciousness at any time of the disease. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern (20 cellslmm, 90% lymphocytes, 5% mononuclear, 3% plasma cells, 2% neutrophils), glucose 56 mg/dl, and protein 25 mg/dl; and negative stain and culture. One month later he was referred to our hospital with Videotape segments accompany the article. Address correspondence and reprint requests to Dr. R. S. C. Alves at Departamento de Neurologia, 5.0 andar, Hospital das Clinicas, Faculdade de Medicina, Universidade de SPo Paulo, Av. Dr. Eneas de Carvalho Aguiar s.n. 05403 SPo Paulo SP, Brazil.
178
179
POSTVACCINAL PARKINSONISM
FIG. 1. MRI shows hyperintense signals affecting the substantia nigra bilaterally, greater on the left side.
moderate and a mild bradykinesia is present on the left side, but there is little dysarthria and hypomimia. The patient is able to walk and run, as well as to eat and attend to personal hygiene. He can draw, and write some letters and numbers. He is currently receiving bromocriptine (25 mg/day), levodopa (125 mg/day), and deprenyl (10 mg/day). A 24-h interruption of levodopa resulted in a marked increase of the parkinsonism, indicating the persistence of the disorder.
DISCUSSION This child is an unusual case of postvaccinal parkinsonism, which began 2 weeks after the vaccination with attenuated live measles vaccine. The virus was cultured in chick embryo tissue; the viral strains were Muraten or Schwarz. The parkinsonism is still present 2 years after its onset. It appears that many viruses can produce parkinsonism (1). Encephalitis lethargica was the first type of epidemic encephalitis to be fully recognized, and for this reason both terms were considered synonymous. Thereafter, in addition to encephalitis lethargica (or type A), other viral encephalitides were found to induce parkinsonism, such as Japanese B encephalitis (2,3), St. Louis encephalitis (4), Eastern equine encephalitis (9,Western equine encephalitis (6), and even poliomyelitis (7). Parkinsonian features have likewise been noted in encephalitis due to measles and varicella, but such instances are relatively rare and all are transient (8,9). In the case described here, the child had fever, without any cutaneous abnormalities, 15 days after a vaccine shot for measles and then developed parkinsonism that has been present up to now, 2 years later. To the best of our knowledge, there is no report in the literature of postvaccinal parkinsonism. Hypomimia, rigidity, and distur-
bances of gait and posture in the acute phase of encephalitis due to measles, varicella, poliomyelitis, and arb0 viruses are usually transient. No more than 10 cases in the United States and Canada are considered to be parkinsonian-like residuals of viral encephalitis (1). There are also two reports of parkinsonism following infections of the nervous system by other viruses: one after herpes ophthalmicus (lo), and the other after a meningoencephalitis due to Coxsackie B Virus (1 1). Another report of postinfectious parkinsonism is one that followed “mild” influenza (12), although the features were transient. In encephalitis lethargica, a viral agent was never identified, though the clinical and pathological features were typical of viral infection. Lymphocytic pleocytosis in the cerebrospinal fluid occurred in over half of the patients (13), as also described in this report. The substantia nigra lesion alone in the case presently reported, as disclosed by MRI, is a unique finding, as it points to a perfect clinicalpathological relationship. The response to levodopa was good, but the appearance of the dyskinesias occurred at a low dosage. This is in agreement with the literature, inasmuch as postencephalitic patients respond better to levodopa, but the adverse reactions tend to occur at a lower dosage (14,15). The fair response to deprenyl in this case is another interesting aspect, as we have not found any report of encephalitic parkinsonism being treated with this drug. Acknowledgment: We are grateful to Drs. J. C. Papaterra Limongi, Luiz R. Comerlatti, Paulo Caramelli, Monica S . Haddad, and Cesar Timo-Iariafor their suggestions. Our special gratitude is hereby expressed to Dr. Stanley Fahn for encouragement to report the case.
LEGENDS TO VIDEOTAPE Segment 1. Day of admission to the hospital. Segment 2. Two years after the onset of disease, on levodopa therapy. Segment 3. Worsening of parkinsonism during a 24-h interruption of levodopa therapy.
REFERENCES 1 . Duvoisin RC, Yahr MD. Encephalitis and parkinsonism. Arch Neurol 1965;12:227-239. 2. Kaneko R. On epidemic encephalitis which occurred in Japan in 1924. Jpn Med World 1925;5:237-241. 3. Goto A. Follow-up study of Japanese B encephalitis. Psychiatr Neurol Jpn 1962;64:236-286. 4. Bredeck JF, et al. Follow-up studies of 1933 St. Louis Epidemic of Encephalitis. JAMA 1938;111:15-17. 5 . Chambers BA, Levey GS. Studies of Eastern encephalitis. Paper presented at the 13th Annual Meeting of the American Academy of Neurology, Detroit, 1961. 6. Adamson JD, Dubo S . Clinical findings in encephalitis (Western Equine). Can J Public Health 1942;32:288. 7. Warembourg H, et al. Syndrome Parkinsonien: SCquelle d’une poliomyelite aigne a forme d’encephalite 1’Cthargique chez un enfant de 20 mois. Sem Hop Paris 1962;38:22992307. 8. Kurland LT. Epidemiology: incidence, geographic distribution and genetic considerations. In: Fields WS, ed. Patho-
Movement Disorders, Vol. 7, N o . 2, 1992
R . S . C . ALVES E T A L .
9. 10.
11. 12.
genesis and treatment of Parkinsonism. Springfield: Charles Thomas Publisher, 1958. Meyer B. Encephalitis after measles with severe parkinsonian rigidity: recovery. Br Med J 1943;1:508. Strong G. Parkinson’s syndrome following severe herpes ophthalmicus. Br Med J 1952;1:533. Walters JH. Postencephalitic Parkinson syndrome after meningoencephalitis due to Coxsackie virus group B. N Engl J Med 1960;230:74&747. Isgreen WP, Chutorian AM, Fahn S. Sequential parkinson-
Movement Disorders, Vol. 7, No. 2, 1992
ism and chorea following “mild” influenza. Trans Am Neurol Assoc 1976;101:5&59. 13. Krusz JC, Koller WC, Ziegler DK. Historical review. Abnormal movements associated with epidemic encephalitis lethargica. Mov Disord 1987;2:137-141. 14. Duvoisin RC, Cabo-Antanes J, Yahr MD. The response of patients with postencephalitic parkinsonism to levodopa. J Neurol Neurosurg Psychiatr 1972;35:487-495. 15. Calne DB, Stern GM, Sharkey J. L-Dopa in postencephalitic parkinsonism. Lancet 1969;1:744-746.
