Early Identification and Treatment: Our patient began immunotherapy on HD7 at our facility; however...
1
Early Identification and Treatment: Our patient began immunotherapy on HD7 at our facility; however he had been seen several times in another hospital 2 weeks prior to his transfer. It is possible that if recognition of the symptoms and test for anti-NMDA antibody had been sent in the other hospital the patient might have been able to receive his immunotherapy earlier. We decided to commence the immunotherapy prior to the confirmatory report of positive anti-NMDA receptor antibody, purely based on his clinical presentation. Even so, the patient still suffered a prolonged and complicated hospital course. Previous studies indicated that the average time from the start of immunotherapy until the first sign of improvement is about 11.5 days if therapy was initiated early (within 3-4 days of symptom onset). The variation in clinical outcome observed in previously published cases appears to correspond to the rapidity of commencing treatment (2). The difficulty again with early initiation is recognition of subtle symptoms as autoimmune encephalitis rather than viral origins or overt psychosis. Associated Tumors: Identification of NMDAR antibodies confirms the diagnosis of the disorder and should lead to the search for a tumor which, if present, is almost always an ovarian teratoma that contains nervous tissue and expresses NMDAR (10). As noted in previous series and case reports, most children with anti NMDAR encephalitis do not have an underlying tumor (only 31% of children < 18 and 9% in children < 14 have an ovarian teratoma). The frequency and duration of tumor surveillance in children is a question that needs to be answered in the future, but in general both age and sex should be taken into consideration. In female patients 12 years or older, a screening approach similar to that of paraneoplastic syndromes is appropriate (ex: MRI of the abdomen and pelvis q6 months x 4 years) but in children <12 and male, the need for repeat screening is unclear (10). Prognosis: When teratoma resection and first line immunotherapy (steroids, IVIG, plasma exchange) fail, second line immunotherapy including rituximab and cyclophosphamide is usually effective. Despite the severity of the disease, patients often improve after intensive care support, immunotherapy, and lengthy hospital stays with multidisciplinary care. Findings have shown that immunotherapy and tumor removal, if applicable, result in substantial neurological improvement in 81% of patients after a median follow up of 24 months. Despite the severity of symptoms and aggressive therapy, frequently positive outcomes are seen. Residual symptoms usually reflect frontolimbic dysfunction, including poor attention and planning, impulsivity, and behavioral disinhibition. However, long term follow up shows that in many patients these symptoms continue to improve, with behavioral problems, decrease of verbal output, and social interactions being the last to recover (5). Psychometric evaluation: As it was with the case described above, many of the symptoms of anti NMDAR encephalitis can be disturbing to parents, nurses, and even novel physicians. Having a standard method by which symptoms are graded and followed over the course of the disease may help both parents and caretakers focus on the subtle improvements and provide a clear overview of recovery. Some psychometric scales used in previous studies are the pediatric cerebral performance category (PCPC) scale, GCS, pediatric anesthesia emergence delirium (PAED) scale, MMSE, and Pediatric Acute Neruopsychiartric Symptom (PANS) scale . Because of the sometimes waxing and waning nature of the disease, patients, parents, and physicians may all benefit from a more structured approach when it comes to evaluating patients’ symptoms Learning points: •Anti-NMDAR encephalitis is a rapidly progressive disease that may initially mimic viral etiology and the subtle neuropsychiatric symptoms may be difficult to discern in children. •Recognition of this disease is important because of its potentially reversible nature, and it is often confused with viral etiology, when in reality, its frequency surpasses that of any specific viral cause of encephalitis in young individuals. •Early and aggressive initiation of immunosuppressive therapy based on symptomatology may provide for a less complicated and severe disease course, sparing the patient a prolonged hospital stay. •Even with very serious disease and complicated hospital courses, when treated aggressively some patients with this condition may still experience near complete recovery like our patient. •Although there are more recent cases described in children with and without tumors, tumor surveillance remains an important part of workup and appropriate follow up surveillance for children needs to be established. •Patients and physicians may benefit from an objective grading of symptoms as they often wax and wane and it may be difficult to assess the progress otherwise. Abstract Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune disease that mimics viral encephalitis in its initial presentation but carries a much higher mortality rate. Here we present a 9 year old boy with anti-NMDA encephalitis who suffered a complicated hospital course including neuropsychiatric presentation, recurrent status epilepticus, respiratory failure, uncontrollable choreoathetoid movements, difficulty swallowing, and cognitive impairment. However, with prolonged intensive care and rehabilitation he made an almost complete recovery. We demonstrate here the importance of early recognition and diagnose of anti- NMDAR encephalitis and its potential for recovery after prolonged intensive care and rehabilitation. Anti N-methyl-D-aspartate receptor encephalitis: A Severe and Complex Autoimmune Disease Anitha Ezekiel, M.D. and Ching H. Wang, M.D., Ph.D. PGY2, Driscoll Children’s Hospital Recovery Remainder of patient’s stay focused on improvement in oral intake and speech, physical, and occupational therapy. Patient was able to take pureed foods by mouth, stand and take some steps with assistance, and sit without support by the time of discharge. He was still without expressive language at time of discharge and mostly would make humming noises. MRI prior to discharge showed almost total recovery from his previous lesions and EEG with some background slowing but no epileptiform discharges. Patient discharged to Ronald McDonald House to continue intensive outpatient rehab at our facility. He was last seen in follow up clinic 1 yr after onset of symptoms at which time he was noted to be doing well, he was back in school and about 1-2 years behind academically but is able to converse and ask and answer questions appropriately. He has normal mood and affect however he continues to be more emotional than his baseline prior to illness and has no memory of his illness. He has had no seizures since his was transferred out of ICU. He continues to have some myoclonic jerks during sleep but no other movement diosrder. Introduction Anti-NMDAR encephalitis is an autoimmune disease associated with antibodies against NMDA receptor, resulting in characteristic neuropsychiatric symptoms. It affects a wide range of ages (8 mo-76 yrs), with 25-40% of patients younger than 18 y. o. and median age of onset of 23 y. o. (4, 9). In several large studies comparing adults to adolescents and children, it has been suggested that in children, the first symptom may be more neurologic (including unilateral dystonia, progressive language disintegration, or status epileptics) vs more psychiatric in adults (including anxiety, agitation, bizarre behavior, delusional or paranoid thoughts, and auditory or visual hallucinations) (1, 5). In younger children, the behavioral change may be more difficult to detect with increased temper tantrums, hyperactivity, or irritability as opposed to frank psychosis. The purpose of presenting this case is to draw out the unique and often severe course of this disease and various aggressive therapies that may need to be employed in order to abate symptoms. It also emphasizes the importance of including this disease as a differential diagnosis in children with unexplained encephalopathies, regardless of age, and the benefit of early and aggressive treatment. We hope by sharing this case, the clinician will be able to better identify anti-NMDAR encephalitis and be more prepared in treating and counseling families on the often distressing symptoms. Case Report A 9 y.o. male with no significant PMH, presents with worsening confusion and seizure episodes for 2 weeks. Patient’s first seizure was at school after complaining of headache and dizziness. Patient did not recognize his mother and was speaking gibberish. After 2 short admissions to an outside hospital ICU and a diagnosis of migraine headaches with subsequent treatment with Topamax, patient continued to have these seizure episodes marked by staring and gibberish talking mimicking psychosis. Due to persistence of his symptoms he was transferred to Driscoll Children’s Hospital ICU for further management. Upon further questioning, there was a pertinent recent history of forgetfulness and not behaving like himself. Also, patient had been complaining of being tired and more sleepy than usual. No history of fever, trauma, drug abuse, recent illness, tick bite, or recent travel. Working diagnosis of encephalitis was considered, though the etiology was unknown. Patient was started on Keppra and acyclovir. Significant Initial Diagnostic Workup: •CSF: 82 wbc (83% lymphocyte), 7 RBC, glucose 72, protein 34 •Arboviral and West Nile virus serology : negative •EEG HD 1: background slowing with focal spike and wave changes in the left temporal area •CSF studies: enterovirus PCR, HSV PCR, acid fast smear, india ink: negative •PPD: negative •Rheumatoid Factor: <10 •Anti dsDNA: negative •ESR: 42 •CSF anti NMDAR antibody test: pending • Lyme antibodies: negative •Multiple Sclerosis panel: 6 oligoclonal band found in CSF Discussion References 1. Armangue, T., Titulaer, M. J., Málaga, I., Bataller, L., Gabilondo, I., Graus, F., et al. (2013). Pediatric Anti-N- methyl-D-Aspartate Receptor Encephalitis—Clinical Analysis and Novel Findings in a Series of 20 Patients. The Journal of Pediatrics, 162(4), 850-856.e2. 2. Breese, E., Dalmau, J., Lennon, V., Apiwattanakul, M., & Sokol, D. (2010). Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Early Treatment is Beneficial. Pediatric Journal of Neurology, 42, 213-214. 3. Bseikri, M. R., Barton, J. R., Kulhanjian, J. A., Dalmau, J., Cohen, R. A., Glaser, C. A., et al. (2012). Anti-N- methyl D-Aspartate Receptor Encephalitis Mimics Viral Encephalitis. The Pediatric Infectious Disease Journal, 31(2), 202- 204. 4. CantarÃn-Extremera, V., Duat-RodrÃguez, A., González- Gutiérrez-Solana, L., López-MarÃn, L., & Armangue, T. (2013). Clinical Case of Anti-N-methyl-d-aspartate Receptor Encephalitis in an 8-Month-Old Patient With Hyperkinetic Movement Disorder. Pediatric Neurology, 48(5), 400-402. 5. Florance-Ryan, N., & Dalmau, J. (2010). Update on anti-N- methyl-D-aspartate receptor encephalitis in children and adolescents. Current Opinion in Pediatrics, 22(6), 739-744. 6. Goldberg, E., Taub, K., Kessler, S., & Abend, N. (2011). Anti-NMDA Receptor Encephalitis Presenting with Focal Non- Convulsive Status Epilepticus in a Child. Neuropediatrics, 42(05), 188-190. 7. Iadisernia, E., Battaglia, F., Vanadia, E., Trapolino, E., Vincent, A., & Biancheri, R. (2012). Anti-N-Methyl-D- Aspartate-receptor encephalitis: cognitive profile in two children. Journal of the European Paediatric Neurology Society, 16, 79- 82. 8. Poloni, C., Korff, C., Ricotti, V., King, M., Perez, E., Mayor-Dubois, C., et al. (2010). Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbance: evidence for anti-N-methyl-D-aspartate receptor encephalitis. Developmental Medicine and Child Neurology, 52, 78-82. 9. Riet, E. H., Esseveld, M. M., Cuypers, L., & Schieveld, J. N. (2013). Anti-NMDAR encephalitis: a new, severe and challenging enduring entity. European Child & Adolescent Psychiatry, 22(5), 319-323. 10.Titulaer, M. J., Graus, F., Kawachi, I., Benseler, S. M., Honig, L. S., Iizuka, T., et al. (2013). Treatment and prognostic factors for long-term outcome in patients with Texas Pediatric Society Electronic Poster Contest Psycho-emotional changes and cognitive impairments: On initial exam, patient was alert, awake and interactive. He was confused but was able to converse. Cognitive function was impaired, he did not have insight and was not able to spell simple words such as "bus" or "boy". He did some simple one digit addition correctly but could not do any multiplication which he was able to before. He answered many simple questions with "I don't remember". Later he was noted to be more emotional, becoming easily upset and crying often. He was giggly, constantly laughing at TV shows inappropriately. On hospital day (HD) 5 he became intermittently irritable and agitated, exhibiting some signs of visual hallucination with staring off, pointing, and screaming. He appeared to be more confused and would not answer any questions. Insomnia and Movement Disorder: Patient developed insomnia 1 week into hospitalization, and was also noted to be increasingly encephalopathic, exhibiting combativeness, kicking staff, urinating on the floor, and thrashing in bed for several days with only 1-2 hours of sleep in between. Several medications employed to calm patient down including benadryl, Ativan, Haldol, Risperdal and Klonopin, all without sustained success. Patient continued to show agitation and worsening choreoathetoic movements. Tetrabenazine was later added which showed some effects in controlling his movements. Seizures: On HD 25, patient had an episode of bradycardia and respiratory distress so was transferred back to the ICU. EEG showed frequent bursts of spike and wave activities. The patient was given 20mg/kg Valproic Acid (VPA) and was then set up for continuous EEG monitoring which revealed near continuous spike and wave activity. Patient was intubated and placed on Pentobarbital coma. He was initially extubated after two days but then continued to have periods of status epilepticus and was again placed on ventilator and propofol drips for control of his seizures. At this time we decided to treat him with 6 cycles of plasmapheresis. He required a extremely high dose of VPA at 25 mg/kg/dose q 4 hours (150 mg/kg/day, 5 times the normal therapeutic dose) in therapeutic levels between 80-120. He was eventually weaned off ventilator on HD 50 and transferred to the floor on HD 53 with no further seizure activity. Interval Studies: HD 13, anti NMDA receptor antibody test came back positive. Repeat MRI after initiation of treatment showed improved temporal lobe lesion but with several new areas of T2 flare hyperintensity on bilateral cerebellum. Tumor surveillance was done including Chest CT and abdominal ultrasound which were read as normal. Pharmacologic Treatment: 1. Seizures 2. Insomnia 3. Movement disorder 4. Immunotherapy Max dose : VPA 25 mg/kg/dose q 4 IV (to keep the level at 70-100) Klonopin 2mg q6 po Tetrabenazine 25 mg bid po IVIG 2g/kg over 5 days ( x 2) on HD 7 & 19 Keppra 900 mg q6 IV (144mg/kg/day) Clonidine 0.1mg qhs po 750 mg methlypredniso ne x 7 days on HD 14 Propofol 200mcg/kg/min IV 6 cycles Plasmapheresis Hospital Course Figure 1: Examination of the diffusion-weighted images of MRI w/ and w/o contrast demonstrate evidence of restricted diffusion in the posteromedial inferior left temporal lobe. This suggests the presence of ischemia/infarction.
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Transcript of Early Identification and Treatment: Our patient began immunotherapy on HD7 at our facility; however...
Early Identification and Treatment: Our patient began immunotherapy on HD7 at our facility; however he had been seen several times in another hospital 2 weeks prior to his transfer. It is possible that if recognition of the symptoms and test for anti-NMDA antibody had been sent in the other hospital the patient might have been able to receive his immunotherapy earlier. We decided to commence the immunotherapy prior to the confirmatory report of positive anti-NMDA receptor antibody, purely based on his clinical presentation. Even so, the patient still suffered a prolonged and complicated hospital course. Previous studies indicated that the average time from the start of immunotherapy until the first sign of improvement is about 11.5 days if therapy was initiated early (within 3-4 days of symptom onset). The variation in clinical outcome observed in previously published cases appears to correspond to the rapidity of commencing treatment (2). The difficulty again with early initiation is recognition of subtle symptoms as autoimmune encephalitis rather than viral origins or overt psychosis.
Associated Tumors: Identification of NMDAR antibodies confirms the diagnosis of the disorder and should lead to the search for a tumor which, if present, is almost always an ovarian teratoma that contains nervous tissue and expresses NMDAR (10). As noted in previous series and case reports, most children with anti NMDAR encephalitis do not have an underlying tumor (only 31% of children < 18 and 9% in children < 14 have an ovarian teratoma). The frequency and duration of tumor surveillance in children is a question that needs to be answered in the future, but in general both age and sex should be taken into consideration. In female patients 12 years or older, a screening approach similar to that of paraneoplastic syndromes is appropriate (ex: MRI of the abdomen and pelvis q6 months x 4 years) but in children <12 and male, the need for repeat screening is unclear (10).
Prognosis: When teratoma resection and first line immunotherapy (steroids, IVIG, plasma exchange) fail, second line immunotherapy including rituximab and cyclophosphamide is usually effective. Despite the severity of the disease, patients often improve after intensive care support, immunotherapy, and lengthy hospital stays with multidisciplinary care. Findings have shown that immunotherapy and tumor removal, if applicable, result in substantial neurological improvement in 81% of patients after a median follow up of 24 months. Despite the severity of symptoms and aggressive therapy, frequently positive outcomes are seen. Residual symptoms usually reflect frontolimbic dysfunction, including poor attention and planning, impulsivity, and behavioral disinhibition. However, long term follow up shows that in many patients these symptoms continue to improve, with behavioral problems, decrease of verbal output, and social interactions being the last to recover (5).
Psychometric evaluation: As it was with the case described above, many of the symptoms of anti NMDAR encephalitis can be disturbing to parents, nurses, and even novel physicians. Having a standard method by which symptoms are graded and followed over the course of the disease may help both parents and caretakers focus on the subtle improvements and provide a clear overview of recovery. Some psychometric scales used in previous studies are the pediatric cerebral performance category (PCPC) scale, GCS, pediatric anesthesia emergence delirium (PAED) scale, MMSE, and Pediatric Acute Neruopsychiartric Symptom (PANS) scale . Because of the sometimes waxing and waning nature of the disease, patients, parents, and physicians may all benefit from a more structured approach when it comes to evaluating patients’ symptoms
Learning points:•Anti-NMDAR encephalitis is a rapidly progressive disease that may initially mimic viral etiology and the subtle neuropsychiatric symptoms may be difficult to discern in children.
•Recognition of this disease is important because of its potentially reversible nature, and it is often confused with viral etiology, when in reality, its frequency surpasses that of any specific viral cause of encephalitis in young individuals.
•Early and aggressive initiation of immunosuppressive therapy based on symptomatology may provide for a less complicated and severe disease course, sparing the patient a prolonged hospital stay.
•Even with very serious disease and complicated hospital courses, when treated aggressively some patients with this condition may still experience near complete recovery like our patient.
•Although there are more recent cases described in children with and without tumors, tumor surveillance remains an important part of workup and appropriate follow up surveillance for children needs to be established.
•Patients and physicians may benefit from an objective grading of symptoms as they often wax and wane and it may be difficult to assess the progress otherwise.
Abstract
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune disease that mimics viral encephalitis in its initial presentation but carries a much higher mortality rate. Here we present a 9 year old boy with anti-NMDA encephalitis who suffered a complicated hospital course including neuropsychiatric presentation, recurrent status epilepticus, respiratory failure, uncontrollable choreoathetoid movements, difficulty swallowing, and cognitive impairment. However, with prolonged intensive care and rehabilitation he made an almost complete recovery. We demonstrate here the importance of early recognition and diagnose of anti-NMDAR encephalitis and its potential for recovery after prolonged intensive care and rehabilitation.
Anti N-methyl-D-aspartate receptor encephalitis: A Severe and Complex Autoimmune Disease
Anitha Ezekiel, M.D. and Ching H. Wang, M.D., Ph.D.PGY2, Driscoll Children’s Hospital
RecoveryRemainder of patient’s stay focused on improvement in oral intake and speech, physical, and occupational therapy. Patient was able to take pureed foods by mouth, stand and take some steps with assistance, and sit without support by the time of discharge. He was still without expressive language at time of discharge and mostly would make humming noises. MRI prior to discharge showed almost total recovery from his previous lesions and EEG with some background slowing but no epileptiform discharges. Patient discharged to Ronald McDonald House to continue intensive outpatient rehab at our facility. He was last seen in follow up clinic 1 yr after onset of symptoms at which time he was noted to be doing well, he was back in school and about 1-2 years behind academically but is able to converse and ask and answer questions appropriately. He has normal mood and affect however he continues to be more emotional than his baseline prior to illness and has no memory of his illness. He has had no seizures since his was transferred out of ICU. He continues to have some myoclonic jerks during sleep but no other movement diosrder.
IntroductionAnti-NMDAR encephalitis is an autoimmune disease associated with antibodies against NMDA receptor, resulting in characteristic neuropsychiatric symptoms. It affects a wide range of ages (8 mo-76 yrs), with 25-40% of patients younger than 18 y. o. and median age of onset of 23 y. o. (4, 9). In several large studies comparing adults to adolescents and children, it has been suggested that in children, the first symptom may be more neurologic (including unilateral dystonia, progressive language disintegration, or status epileptics) vs more psychiatric in adults (including anxiety, agitation, bizarre behavior, delusional or paranoid thoughts, and auditory or visual hallucinations) (1, 5). In younger children, the behavioral change may be more difficult to detect with increased temper tantrums, hyperactivity, or irritability as opposed to frank psychosis. The purpose of presenting this case is to draw out the unique and often severe course of this disease and various aggressive therapies that may need to be employed in order to abate symptoms. It also emphasizes the importance of including this disease as a differential diagnosis in children with unexplained encephalopathies, regardless of age, and the benefit of early and aggressive treatment. We hope by sharing this case, the clinician will be able to better identify anti-NMDAR encephalitis and be more prepared in treating and counseling families on the often distressing symptoms.
Case Report
A 9 y.o. male with no significant PMH, presents with worsening confusion and seizure episodes for 2 weeks. Patient’s first seizure was at school after complaining of headache and dizziness. Patient did not recognize his mother and was speaking gibberish. After 2 short admissions to an outside hospital ICU and a diagnosis of migraine headaches with subsequent treatment with Topamax, patient continued to have these seizure episodes marked by staring and gibberish talking mimicking psychosis. Due to persistence of his symptoms he was transferred to Driscoll Children’s Hospital ICU for further management. Upon further questioning, there was a pertinent recent history of forgetfulness and not behaving like himself. Also, patient had been complaining of being tired and more sleepy than usual. No history of fever, trauma, drug abuse, recent illness, tick bite, or recent travel. Working diagnosis of encephalitis was considered, though the etiology was unknown. Patient was started on Keppra and acyclovir.
Significant Initial Diagnostic Workup: •CSF: 82 wbc (83% lymphocyte), 7 RBC, glucose 72, protein 34
•Arboviral and West Nile virus serology : negative
•EEG HD 1: background slowing with focal spike and wave changes in the left temporal area
•CSF studies: enterovirus PCR, HSV PCR, acid fast smear, india ink: negative
•PPD: negative
•Rheumatoid Factor: <10
•Anti dsDNA: negative
•ESR: 42
•CSF anti NMDAR antibody test: pending
• Lyme antibodies: negative
•Multiple Sclerosis panel: 6 oligoclonal band found in CSF
Discussion
References1. Armangue, T., Titulaer, M. J., Málaga, I., Bataller, L., Gabilondo, I., Graus, F., et al.
(2013). Pediatric Anti-N-methyl-D-Aspartate Receptor Encephalitis—Clinical Analysis and Novel Findings in a Series of 20 Patients. The Journal of Pediatrics, 162(4), 850-856.e2.
2. Breese, E., Dalmau, J., Lennon, V., Apiwattanakul, M., & Sokol, D. (2010). Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Early Treatment is Beneficial. Pediatric Journal of Neurology, 42, 213-214.
3. Bseikri, M. R., Barton, J. R., Kulhanjian, J. A., Dalmau, J., Cohen, R. A., Glaser, C. A., et al. (2012). Anti-N-methyl D-Aspartate Receptor Encephalitis Mimics Viral Encephalitis. The Pediatric Infectious Disease Journal, 31(2), 202-204.
4. Cantarà n-Extremera, V., Duat-Rodrà guez, A., González-Gutiérrez-Solana, L., López-Marà n, L., & Armangue, T. (2013). Clinical Case of Anti-N-methyl-d-aspartate Receptor Encephalitis in an 8-Month-Old Patient With Hyperkinetic Movement Disorder. Pediatric Neurology, 48(5), 400-402.
5. Florance-Ryan, N., & Dalmau, J. (2010). Update on anti-N-methyl-D-aspartate receptor encephalitis in children and adolescents. Current Opinion in Pediatrics, 22(6), 739-744.
6. Goldberg, E., Taub, K., Kessler, S., & Abend, N. (2011). Anti-NMDA Receptor Encephalitis Presenting with Focal Non-Convulsive Status Epilepticus in a Child. Neuropediatrics, 42(05), 188-190.
7. Iadisernia, E., Battaglia, F., Vanadia, E., Trapolino, E., Vincent, A., & Biancheri, R. (2012). Anti-N-Methyl-D-Aspartate-receptor encephalitis: cognitive profile in two children. Journal of the European Paediatric Neurology Society, 16, 79-82.
8. Poloni, C., Korff, C., Ricotti, V., King, M., Perez, E., Mayor-Dubois, C., et al. (2010). Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbance: evidence for anti-N-methyl-D-aspartate receptor encephalitis. Developmental Medicine and Child Neurology, 52, 78-82.
9. Riet, E. H., Esseveld, M. M., Cuypers, L., & Schieveld, J. N. (2013). Anti-NMDAR encephalitis: a new, severe and challenging enduring entity. European Child & Adolescent Psychiatry, 22(5), 319-323.
10. Titulaer, M. J., Graus, F., Kawachi, I., Benseler, S. M., Honig, L. S., Iizuka, T., et al. (2013). Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology, 12(2), 157-165.
11. Wong-Kisiel, L. C., Ji, T., Renaud, D. L., Kotagal, S., Patterson, M. C., Dalmau, J., et al. (2010). Response To Immunotherapy In A 20-Month-Old Boy With Anti-Nmda Receptor Encephalitis. Neurology, 74(19), 1550-1551.
12. Special Thanks to Dr. Ching Wang, Pediatric Neurologist at Driscoll Children’s Hospital for all his help and guidance
Texas Pediatric Society Electronic Poster Contest
Psycho-emotional changes and cognitive impairments: On initial exam, patient was alert, awake and interactive. He was confused but was able to converse. Cognitive function was impaired, he did not have insight and was not able to spell simple words such as "bus" or "boy". He did some simple one digit addition correctly but could not do any multiplication which he was able to before. He answered many simple questions with "I don't remember". Later he was noted to be more emotional, becoming easily upset and crying often. He was giggly, constantly laughing at TV shows inappropriately. On hospital day (HD) 5 he became intermittently irritable and agitated, exhibiting some signs of visual hallucination with staring off, pointing, and screaming. He appeared to be more confused and would not answer any questions.
Insomnia and Movement Disorder: Patient developed insomnia 1 week into hospitalization, and was also noted to be increasingly encephalopathic, exhibiting combativeness, kicking staff, urinating on the floor, and thrashing in bed for several days with only 1-2 hours of sleep in between. Several medications employed to calm patient down including benadryl, Ativan, Haldol, Risperdal and Klonopin, all without sustained success. Patient continued to show agitation and worsening choreoathetoic movements. Tetrabenazine was later added which showed some effects in controlling his movements.
Seizures: On HD 25, patient had an episode of bradycardia and respiratory distress so was transferred back to the ICU. EEG showed frequent bursts of spike and wave activities. The patient was given 20mg/kg Valproic Acid (VPA) and was then set up for continuous EEG monitoring which revealed near continuous spike and wave activity. Patient was intubated and placed on Pentobarbital coma. He was initially extubated after two days but then continued to have periods of status epilepticus and was again placed on ventilator and propofol drips for control of his seizures. At this time we decided to treat him with 6 cycles of plasmapheresis. He required a extremely high dose of VPA at 25 mg/kg/dose q 4 hours (150 mg/kg/day, 5 times the normal therapeutic dose) to keep his VPA in therapeutic levels between 80-120. He was eventually weaned off ventilator on HD 50 and transferred to the floor on HD 53 with no further seizure activity.
Interval Studies: HD 13, anti NMDA receptor antibody test came back positive. Repeat MRI after initiation of treatment showed improved temporal lobe lesion but with several new areas of T2 flare hyperintensity on bilateral cerebellum. Tumor surveillance was done including Chest CT and abdominal ultrasound which were read as normal.
Pharmacologic Treatment:
1. Seizures 2. Insomnia 3. Movement disorder
4. Immunotherapy
Max dose:
VPA 25 mg/kg/dose q 4 IV (to keep the
level at 70-100)
Klonopin 2mg q6 po
Tetrabenazine 25 mg bid po
IVIG 2g/kg over 5 days ( x 2) on HD 7
& 19 Keppra 900 mg q6
IV (144mg/kg/day)Clonidine 0.1mg
qhs po 750 mg
methlyprednisone x 7 days on HD 14
Propofol 200mcg/kg/min IV
6 cycles Plasmapheresis
Hospital Course
Figure 1: Examination of the diffusion-weighted images of MRI w/ and w/o contrast demonstrate evidence of restricted diffusion in the posteromedial inferior left temporal lobe. This suggests the presence of ischemia/infarction.
