Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis
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《美国医学杂志》
Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey
Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood and young adolescence due to persistant measles virus infection of the central nervous system. In majority of cases onset occurs from 5-15 years of age.[1] In a nonimmunized population the average onset is 8 years. Children with SSPE had experienced natural infection with the rubeola virus at an early age, half before age 2 years.[2] SSPE generally occurs 5-10 years after measles infection. In the early stages of the disease behavioral and personality changes is followed by myoclonic jerks and convulsions. In late stages dementia, stupor and coma develops. Diagnosis is achieved by typical clinical findings, measles antibody titer increase in cerebrospinal fluid (CSF) and serum, high amplitude, slow, sharp waves in EEG. Prognosis is poor and death ensues in about 3 yr after the diagnosis. Here it is presented a 7-years-old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor. Due to suggestive radiological and clinical findings and a history of recent mumps infection he was thought to have acute disseminated encephalomyelitis initially and given treatment. But due to clinical deterioration and detection of anti measles IgG in serum and CSF, SSPE diagnosis was confirmed. With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically be diverse and a thorough differential diagnosis is mandatory for a definite diagnosis.
Keywords: Subacute sclerosing panencephalitis; Acute disseminated encephalomyelitis; Chronic encephalitis; Childhood
Case report
A 7 years old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor was admitted to our hospital. Fifteen days before the admittance he was hospitalized in another hospital due to mumps infection. Three days after the diagnosis of mumps infection he experienced ataxia and drop attacks with increasing severity.
A history of measles infection at about 1 years of age was obtained. Information about measles vaccination could not be obtained accurately from parents.
His body weight was 22.5 Kg (25-50 p.), height 120 cm (25-50 p.); blood pressure 100/50 mmHg, axillary temperature 36,5oC, pulse 96/min. and respiratory rate 36/min.
In physical examination he had ataxia, involuntary movements in hands. Deep tendon reflexes in lower extremities were increased. Other systemic findings were found to be normal.
Complete blood count, electrolytes, liver and kidney function tests, eryhtrocyte sedimantation rate were in normal ranges. Chest X-ray was normal. Any pathology was not detected in cranial CT imaging.
In lumbar puncture cerebrospinal fluid (CSF) was clear without any type of cell in microscopic examination. CSF protein was 21 mg/dl and glucose 55 mg/dl.
In EEG, sharp waves originating mainly from right and frontal parts of the hemispheres which mixed with the background activity were detected. Epileptic activity characterized with slow, sharp waves was also observed. In video EEG continous sharp waves were detected.
Asymmetric signal changes in cranial MR imaging in periventricular white matter and centrum semiovale [Figure - 1] and history of mumps infection 15 days before admission suggested acute disseminated encephalomyelitis (ADEM) as the initial diagnosis. With a recent history of mumps infection, radiological and clinical findings resembling ADEM, steroid treatment was started. After steroid treatment due to progressive clinical deterioration and the appearance of convulsions, treatment was terminated and other possible etiologies were reevaluated.
With patient's progressive clinical deterioration and a history of measles infection he was thought to have SSPE. After a lumber puncture patient's anti-measles antibodies in serum and CSF were determined. CSF Anti measles IgG was 25, total CSF IgG 5,05mg/dl, serum anti-measles IgG 95, serum total IgG 1430 mg/dl ( Normal values; serum anti-measles antibody (-), CSF anti-measles antibody (-), serum IgG: 460-1600 mg/dl, CSF IgG: 0.8- 3.5mg/dl) . Since the patient's serum and CSF anti-measles IgG were found to be (+) SSPE diagnosis was confirmed [Table - 1].
Discussion
ADEM is an immune-mediated disease developing after immunization, upper respiratory tract infection and infections like varicella, herpes zoster, rubella and mumps. Lethargy, delirium, convulsions, coma, bilateral optic neuritis and myelopathy are among the clinical manifestations of ADEM.[3] In 1999, in Apak and coworkers' study of 10 cases with ADEM, ataxia was the leading symptom followed by optic neuritis, cranial nerve palsies and convulsions.[4] CSF immune tests are moderately positive in minority of monosymptomatic ADEM cases. Highly positive levels are found to be associated with SSPE, neurosyphilis, neuroborreliosis and some leukodystrophies.[5] EEG may be normal and slowing of the rhythm and disturbance of normal sleep pattern may be observed in early stages.[4] In cranial MR imaging typically widespread multifocal lesions characterized by edema,demyelination in white matter, basal ganglia and brain stem may be seen. Some patients respond well to steroid or immunoglobulin therapy.[3]
Due to the recent history of mumps imfection, presence of drop attacks while walking, stupor and typical cranial MR findings, initially our patient was thought to have ADEM and steroid treatment was started. It is stated that response to steroid treatment of ADEM is good and generally majority of patients have full recovery. Despite the typical course of ADEM, due to the patient's unresponsiveness to steroid therapy and progressive neurological deterioration etiologies other than ADEM were evaluated .
Presence of a history of measles infection and the anti-measles antibody positivity in CSF led us to the diagnosis of SSPE.
Though it's rarely encountered in last years, SSPE is the most common type of chronic encephalitis. SSPE usually develops 5-10 years after measles infection. Onset of the disease usually is between 5-15 years of age. SSPE risk increases if measles infection encountered before 18 months of age.[1]
Onset of SSPE is usually before 16 years of age. Later the onset of the disease, less the survival. Bojinava et al in their study of 40 cases with SSPE found that average time of measles infection, first age of diagnosis and the latent period between measles and SSPE was 16 months, 8-11 years and 7 years respectively.[6] The authors patient's history of measles infection at 1 years of age and 7-years of age of diagnosis concorded with literature.
In case of myoclonic convulsions, intellectual deterioration and typical EEG findings SSPE is suspected. Diagnosis is confirmed by demonstrating serum and CSF measles antibodies. CSF protein in SSPE is usually normal or minimally elevated. CSF protein more than 90 mg/dl suggest other pathologies than SSPE. Our patient's CSF protein level was 21mg/dl suggesting SSPE. Treatable causes like bacterial infection and tumors should be ruled out in differential diagnosis. Cerebral storage diseases, polydystrophies, leukodystrophies and demyelinating diseases may also cause progressive dementia, convulsions and paralisy. In early stages atypical viral encephalopathies should be considered in differential diagnosis of SSPE. Other slow virus infections should also be ruled out.[1]
Cranial CT in early stages of SSPE is almost always normal. Signs like widespread brain edema, white matter hypodensities are found in late stages.[7] Their patient's cranial CT was found to be normal. Though it's stated that MR imaging is more sensitive than CT in early stages, only mild changes can be observed.[8] With MR imaging abnormal signal increase is observed in SSPE. Abnormal signals in MR may reflect demyelination and gliosis. In authors patient's MR imaging asymmetric signal changes in periventricular white matter and centrum semiovale were detected. In a study of Gruppo J in 2003, the cranial CT of 4 patients with SSPE were found to be normal . In same four patient's cranial MR imaging disseminated hyperintense lesions were obtained.[9]
EEG is caharacteristic in SSPE. Periodic burst of high amplitude, sharp waves is found in EEG. In the same study of ztürk et al in 2002 typical periodic complexes were found in EEG.[10] While sharp and slow waves were observed in our patient's EEG; in video EEG continous sharp waves were observed.
It's not easy to differentiate ADEM from the first episodes of Multiple sclerosis; it's also hard to differentiate ADEM from other inflammatory encephalopaties. Some encephalitis like herpes and measles may mimic ADEM. In 1997 Arora et al reported a case with atypical CSF findings, cranial MR and EEG findings, presenting initially as ADEM but diagnosed as SSPE later on. In cranial MR imaging of 16 years old patient with complaints of behavioral changes, progressively deteriorating with neurological findings of tetraparesia, increased deep tendon reflexes, clonus; diffuse signal increase in periventricular areas and pons was observed leading to diagnosis of ADEM. Though steroid treatment was started, due to progressive neurological deterioration leading to death SSPE diagnosis was made after brain biopsy.[11]
The authors patient was also considered to have ADEM and given steroid therapy, due to the history of mumps infection 15 days before and acute onset of symptoms and findings resembling ADEM in cranial MR imaging. But after progressive neurological deterioration and unresponsiveness to steroid therapy with positive serum and CSF measles antibodies SSPE diagnosis was confirmed.
With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically be diverse and a thorough differential diagnosis is mandatory for a definite diagnosis.
References
1.Maldonado Y. Subacute sclerosing panencephalitis. In Behrman RE; Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics . 17 th edition. Philadelphia: WB Saunders, 2004: 1030-1031.
2.Fenichel GM. Subacute sclerosing panencephalitis. In Fenichel GM, ed. Clinical Pediatric Neurology . 4th edition. Philadelphia: WB Saunders, 2001:142.
3.Johnston M.V. Encephalopathies. In Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics . 17 th edition. Philadelphia: WB Saunders, 2004: 2027-2028.
4.Apak RA, Kose G, Anlar B, Turanli G, Topaloglu H, Ozdirim E. Acute disseminated encephalomyelitis in childhood:report of 10 cases. J Child Neurol 1999; 14 : 198-201. [PUBMED]
5.Rust RS, Dodson WE, Trotter JL. Cerebrospinal fluid IgG in childhood : the establishment of reference values. Ann Neurol 1988; 23: 406-410.
6.Bojinova V. et al. Clinical and epidemiological characteristics of subacute sclerosing panencephalitis in Bulgaria during the past 25 years (1978-2002). Eur J Pediatr Neurol 2004; 8: 89-94.
7.Duda EE, Huttenlocher PR, Patronas NJ. CT of subacute sclerosing panencephalitis. AJNR 1980;1(1) : 35-38.
8.Miller D.H. et al. Magnetic resonance imaging of inflammatory and demyelinating white matter diseases of children. Dev Med Child Neur 1990;32: 97-107.
9.Grippo J, Caceres L, Asis A, Grippo T, Ruprecht B, Lopez M. Subacute sclerosing panencephalitis : fulminant form. Rev Neurol 2003; 36 : 536-539. [PUBMED] [FULLTEXT]
10.ztürk A, Gürses C, Baykan B, G φkyiπit A, Eraksoy M. Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients. J Child Neurol 2002; 17: 25-29.
11.Arora SC, Al-Tahan AR, Al-Zeer A, Al-Tahan F, Ozo CO, ur-Rahman N. Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis: a case report. J Neurol Sci 1997; 146: 13-18.(Comert Serdar, Vitrinel Ayca, Gursu Hazi)
Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood and young adolescence due to persistant measles virus infection of the central nervous system. In majority of cases onset occurs from 5-15 years of age.[1] In a nonimmunized population the average onset is 8 years. Children with SSPE had experienced natural infection with the rubeola virus at an early age, half before age 2 years.[2] SSPE generally occurs 5-10 years after measles infection. In the early stages of the disease behavioral and personality changes is followed by myoclonic jerks and convulsions. In late stages dementia, stupor and coma develops. Diagnosis is achieved by typical clinical findings, measles antibody titer increase in cerebrospinal fluid (CSF) and serum, high amplitude, slow, sharp waves in EEG. Prognosis is poor and death ensues in about 3 yr after the diagnosis. Here it is presented a 7-years-old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor. Due to suggestive radiological and clinical findings and a history of recent mumps infection he was thought to have acute disseminated encephalomyelitis initially and given treatment. But due to clinical deterioration and detection of anti measles IgG in serum and CSF, SSPE diagnosis was confirmed. With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically be diverse and a thorough differential diagnosis is mandatory for a definite diagnosis.
Keywords: Subacute sclerosing panencephalitis; Acute disseminated encephalomyelitis; Chronic encephalitis; Childhood
Case report
A 7 years old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor was admitted to our hospital. Fifteen days before the admittance he was hospitalized in another hospital due to mumps infection. Three days after the diagnosis of mumps infection he experienced ataxia and drop attacks with increasing severity.
A history of measles infection at about 1 years of age was obtained. Information about measles vaccination could not be obtained accurately from parents.
His body weight was 22.5 Kg (25-50 p.), height 120 cm (25-50 p.); blood pressure 100/50 mmHg, axillary temperature 36,5oC, pulse 96/min. and respiratory rate 36/min.
In physical examination he had ataxia, involuntary movements in hands. Deep tendon reflexes in lower extremities were increased. Other systemic findings were found to be normal.
Complete blood count, electrolytes, liver and kidney function tests, eryhtrocyte sedimantation rate were in normal ranges. Chest X-ray was normal. Any pathology was not detected in cranial CT imaging.
In lumbar puncture cerebrospinal fluid (CSF) was clear without any type of cell in microscopic examination. CSF protein was 21 mg/dl and glucose 55 mg/dl.
In EEG, sharp waves originating mainly from right and frontal parts of the hemispheres which mixed with the background activity were detected. Epileptic activity characterized with slow, sharp waves was also observed. In video EEG continous sharp waves were detected.
Asymmetric signal changes in cranial MR imaging in periventricular white matter and centrum semiovale [Figure - 1] and history of mumps infection 15 days before admission suggested acute disseminated encephalomyelitis (ADEM) as the initial diagnosis. With a recent history of mumps infection, radiological and clinical findings resembling ADEM, steroid treatment was started. After steroid treatment due to progressive clinical deterioration and the appearance of convulsions, treatment was terminated and other possible etiologies were reevaluated.
With patient's progressive clinical deterioration and a history of measles infection he was thought to have SSPE. After a lumber puncture patient's anti-measles antibodies in serum and CSF were determined. CSF Anti measles IgG was 25, total CSF IgG 5,05mg/dl, serum anti-measles IgG 95, serum total IgG 1430 mg/dl ( Normal values; serum anti-measles antibody (-), CSF anti-measles antibody (-), serum IgG: 460-1600 mg/dl, CSF IgG: 0.8- 3.5mg/dl) . Since the patient's serum and CSF anti-measles IgG were found to be (+) SSPE diagnosis was confirmed [Table - 1].
Discussion
ADEM is an immune-mediated disease developing after immunization, upper respiratory tract infection and infections like varicella, herpes zoster, rubella and mumps. Lethargy, delirium, convulsions, coma, bilateral optic neuritis and myelopathy are among the clinical manifestations of ADEM.[3] In 1999, in Apak and coworkers' study of 10 cases with ADEM, ataxia was the leading symptom followed by optic neuritis, cranial nerve palsies and convulsions.[4] CSF immune tests are moderately positive in minority of monosymptomatic ADEM cases. Highly positive levels are found to be associated with SSPE, neurosyphilis, neuroborreliosis and some leukodystrophies.[5] EEG may be normal and slowing of the rhythm and disturbance of normal sleep pattern may be observed in early stages.[4] In cranial MR imaging typically widespread multifocal lesions characterized by edema,demyelination in white matter, basal ganglia and brain stem may be seen. Some patients respond well to steroid or immunoglobulin therapy.[3]
Due to the recent history of mumps imfection, presence of drop attacks while walking, stupor and typical cranial MR findings, initially our patient was thought to have ADEM and steroid treatment was started. It is stated that response to steroid treatment of ADEM is good and generally majority of patients have full recovery. Despite the typical course of ADEM, due to the patient's unresponsiveness to steroid therapy and progressive neurological deterioration etiologies other than ADEM were evaluated .
Presence of a history of measles infection and the anti-measles antibody positivity in CSF led us to the diagnosis of SSPE.
Though it's rarely encountered in last years, SSPE is the most common type of chronic encephalitis. SSPE usually develops 5-10 years after measles infection. Onset of the disease usually is between 5-15 years of age. SSPE risk increases if measles infection encountered before 18 months of age.[1]
Onset of SSPE is usually before 16 years of age. Later the onset of the disease, less the survival. Bojinava et al in their study of 40 cases with SSPE found that average time of measles infection, first age of diagnosis and the latent period between measles and SSPE was 16 months, 8-11 years and 7 years respectively.[6] The authors patient's history of measles infection at 1 years of age and 7-years of age of diagnosis concorded with literature.
In case of myoclonic convulsions, intellectual deterioration and typical EEG findings SSPE is suspected. Diagnosis is confirmed by demonstrating serum and CSF measles antibodies. CSF protein in SSPE is usually normal or minimally elevated. CSF protein more than 90 mg/dl suggest other pathologies than SSPE. Our patient's CSF protein level was 21mg/dl suggesting SSPE. Treatable causes like bacterial infection and tumors should be ruled out in differential diagnosis. Cerebral storage diseases, polydystrophies, leukodystrophies and demyelinating diseases may also cause progressive dementia, convulsions and paralisy. In early stages atypical viral encephalopathies should be considered in differential diagnosis of SSPE. Other slow virus infections should also be ruled out.[1]
Cranial CT in early stages of SSPE is almost always normal. Signs like widespread brain edema, white matter hypodensities are found in late stages.[7] Their patient's cranial CT was found to be normal. Though it's stated that MR imaging is more sensitive than CT in early stages, only mild changes can be observed.[8] With MR imaging abnormal signal increase is observed in SSPE. Abnormal signals in MR may reflect demyelination and gliosis. In authors patient's MR imaging asymmetric signal changes in periventricular white matter and centrum semiovale were detected. In a study of Gruppo J in 2003, the cranial CT of 4 patients with SSPE were found to be normal . In same four patient's cranial MR imaging disseminated hyperintense lesions were obtained.[9]
EEG is caharacteristic in SSPE. Periodic burst of high amplitude, sharp waves is found in EEG. In the same study of ztürk et al in 2002 typical periodic complexes were found in EEG.[10] While sharp and slow waves were observed in our patient's EEG; in video EEG continous sharp waves were observed.
It's not easy to differentiate ADEM from the first episodes of Multiple sclerosis; it's also hard to differentiate ADEM from other inflammatory encephalopaties. Some encephalitis like herpes and measles may mimic ADEM. In 1997 Arora et al reported a case with atypical CSF findings, cranial MR and EEG findings, presenting initially as ADEM but diagnosed as SSPE later on. In cranial MR imaging of 16 years old patient with complaints of behavioral changes, progressively deteriorating with neurological findings of tetraparesia, increased deep tendon reflexes, clonus; diffuse signal increase in periventricular areas and pons was observed leading to diagnosis of ADEM. Though steroid treatment was started, due to progressive neurological deterioration leading to death SSPE diagnosis was made after brain biopsy.[11]
The authors patient was also considered to have ADEM and given steroid therapy, due to the history of mumps infection 15 days before and acute onset of symptoms and findings resembling ADEM in cranial MR imaging. But after progressive neurological deterioration and unresponsiveness to steroid therapy with positive serum and CSF measles antibodies SSPE diagnosis was confirmed.
With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically be diverse and a thorough differential diagnosis is mandatory for a definite diagnosis.
References
1.Maldonado Y. Subacute sclerosing panencephalitis. In Behrman RE; Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics . 17 th edition. Philadelphia: WB Saunders, 2004: 1030-1031.
2.Fenichel GM. Subacute sclerosing panencephalitis. In Fenichel GM, ed. Clinical Pediatric Neurology . 4th edition. Philadelphia: WB Saunders, 2001:142.
3.Johnston M.V. Encephalopathies. In Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics . 17 th edition. Philadelphia: WB Saunders, 2004: 2027-2028.
4.Apak RA, Kose G, Anlar B, Turanli G, Topaloglu H, Ozdirim E. Acute disseminated encephalomyelitis in childhood:report of 10 cases. J Child Neurol 1999; 14 : 198-201. [PUBMED]
5.Rust RS, Dodson WE, Trotter JL. Cerebrospinal fluid IgG in childhood : the establishment of reference values. Ann Neurol 1988; 23: 406-410.
6.Bojinova V. et al. Clinical and epidemiological characteristics of subacute sclerosing panencephalitis in Bulgaria during the past 25 years (1978-2002). Eur J Pediatr Neurol 2004; 8: 89-94.
7.Duda EE, Huttenlocher PR, Patronas NJ. CT of subacute sclerosing panencephalitis. AJNR 1980;1(1) : 35-38.
8.Miller D.H. et al. Magnetic resonance imaging of inflammatory and demyelinating white matter diseases of children. Dev Med Child Neur 1990;32: 97-107.
9.Grippo J, Caceres L, Asis A, Grippo T, Ruprecht B, Lopez M. Subacute sclerosing panencephalitis : fulminant form. Rev Neurol 2003; 36 : 536-539. [PUBMED] [FULLTEXT]
10.ztürk A, Gürses C, Baykan B, G φkyiπit A, Eraksoy M. Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients. J Child Neurol 2002; 17: 25-29.
11.Arora SC, Al-Tahan AR, Al-Zeer A, Al-Tahan F, Ozo CO, ur-Rahman N. Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis: a case report. J Neurol Sci 1997; 146: 13-18.(Comert Serdar, Vitrinel Ayca, Gursu Hazi)