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Hashimoto's encephalopathy: a case report with neuropsychological testing
General Hospital Psychiatry 29 (2007) 267 – 269
Case Reports
Hashimoto’s encephalopathy: a case report with neuropsychological testing Ronnie R. Cummings, M.D., Steven C. Bagley, M.S., M.D.4, Saba Syed, M.D., Natalie Dong, Ph.D., Alex Lin, M.D. Department of Psychiatry, 6D-129, Olive View — UCLA Medical Center, Sylmar, CA 91342, USA Received 22 September 2006; accepted 2 January 2007
Abstract We report a case of Hashimoto’s encephalopathy with detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the deficits and their response to treatment. It highlights that behavioral and psychotic symptoms remit before cognitive deficits and suggests that the latter may be more appropriate for guiding the duration of steroid treatment. D 2007 Elsevier Inc. All rights reserved. Keywords: Hashimoto’s encephalopathy; Steroid responsive psychosis; Neuropsychological testing
1. Introduction Hashimoto’s encephalopathy is a rare syndrome characterized by altered mental status, positive antithyroid antibodies and clinical response to glucocorticoid therapy [1]. The first recognized case appeared in a 1966 report by Brain, Jellinek and Ball, who described a patient with seizures, disorientation, stroke-like episodes and fluctuating hemiparesis, along with increased cerebrospinal fluid (CSF) protein, transient electroencephalogram (EEG) abnormalities, clinical hypothyroidism and positive antithyroid antibodies [2]. There is still controversy over the association with thyroid dysfunction and the role of autoimmune antibodies, although it is generally believed to be responsive to steroid therapy [3]. The associated neuropsychiatric symptoms are diverse and can include focal neurologic deficits, seizures, confusion, disorientation and psychosis; however, the varied nature and wide spectrum of these symptoms, which overlap considerably with other psychiatric and neurologic disorders, complicates the proper diagnosis. We report here a case in which we were fortunate to acquire detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the
4 Corresponding author. Tel.: +1 818 364 4778; fax: +1 818 364 3554. E-mail address: [email protected] (S.C. Bagley). 0163-8343/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2007.01.003
deficits and their response to treatment. This case also highlights the difficulties in establishing the diagnosis.
2. Case presentation A 19-year-old Hispanic male with no prior neuropsychiatric history presented to a community hospital with confusion, disorientation, agitation and blank staring spells lasting for several minutes that had begun approximately 1 month earlier. During that brief hospitalization, he was diagnosed with absence seizures and aseptic meningitis (despite normal lumbar puncture results) and discharged on a course of phenytoin, depakote and acyclovir. Two weeks later, his family took him to a different community hospital with agitated and combative behavior; he was admitted to the psychiatric unit, treated with an unknown bsedatingQ medication and later signed out by his family against medical advice. After discharge, the patient continued on phenytoin and depakote. Three weeks later, his family brought him to our facility; the patient was still experiencing the staring spells, confusion, disorientation to place and date and agitation leading to physical conflicts with family members. The family reported that the patient had a normal developmental history. Prior to the onset of symptoms, he had been enrolled in community college and was running a small business on the Internet. There was no known prior treatment for any psychiatric disorder, recent head trauma,
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R.R. Cummings et al. / General Hospital Psychiatry 29 (2007) 267 – 269
substance abuse, foreign travel, or infection. A distant cousin had schizophrenia. There were no abnormalities on physical examination. The neurologic exam revealed hyperreflexia in the lower extremities with myoclonus, slowed rapid alternating movements and mildly ataxic gait. The Folstein Mini-Mental State Exam score was 23 out of 30; he was oriented to person and part of the location (the state) but could not name the city, county, date, day of week, month, or year. He could not answer direct questions about mood; his affect fluctuated, and his thought process was notable for disorganization and perseveration on the name of his Internet business. The complete blood count showed mild anemia (hemoglobin = 12 g/dl). The TSH was normal (1.85 AIU/ml). Initial basic chemistry, Rapid Plasma Reagin (RPR), B12, coagulation studies, serum heavy metals (mercury, arsenic, lead), HIV, ammonia level, Antinuclear Antibodies (ANA) titer, lumbar puncture and deep punch biopsy for Lafora’s disease were all within normal limits. An ophthalmologic exam showed no Keyser–Fleischer rings. Head computed tomography and magnetic resonance imaging were also normal. EEG was performed and showed no epileptiform changes, although the patient had one observed episode of staring and drooling and, later, a tonic–clonic seizure, treated first with divalproex, changed to zonisamide because of rising serum transaminase levels. The patient expressed delusional beliefs, thinking that he was God and controlled everything, and was agitated, with flailing and yelling, requiring the use of physical restraints and haloperidol. By the end of the hospitalization, the patient’s agitation had decreased, and he was discharged to home with a prescription for zonisamide. Neuropsychological testing obtained during this hospitalization will be discussed below.
Five days later, the patient’s family brought him back to our facility because he had attacked his mother. Antimicrosomal thyroid antibodies had been sent during the previous hospitalization; those results were noted to be positive at 17.0 U/ml (reference range: b 0.5 U/ml), although the antithyroglobulin antibody test was normal. The patient was diagnosed with Hashimoto’s encephalopathy and treated with iv solumedrol 500 mg daily (later changed to oral prednisone) and olanzapine up to 5 mg twice daily for agitation. The patient’s cognition and behavior improved, and by discharge, he was able to participate in normal, spontaneous conversation; he had not needed medication for agitation during the previous 3 days, and he was discharged to the care of his family. An outpatient EEG shortly after discharge showed moderate 4–6 Hz diffuse slowing and intermittent 1–2 Hz slowing in the bilateral frontotemporal areas. At discharge, the patient was taking prednisone 60 mg/ day and zonisamide 300 mg at night. The prednisone was tapered to 40 mg at 3 weeks, at which point, his behavior was stable; he was grossly oriented, but not back in school, nor had his behavior returned to baseline. At 6 weeks, his prednisone was at 20 mg per day; he was noted to be oriented, his behavior stable, and his conversation was bcoherent and substantial.Q Five months and 3 weeks after discharge, he was again seen. He had been off prednisone for 2 weeks; he was bback to baseline in behavior and intellectQ according to his family and was again running his Internet business; the zonegran dose was lowered to 200 mg at night. He did not return later phone calls to schedule further testing. We were able to perform neuropsychological testing during the first hospitalization before the diagnosis of
Table 1 Summary of neuropsychological test results for patient with Hashimoto’s encephalopathy Test
Date of testing October 4, 2005 Raw score
CASI-S (mental status) Trails A (simple visuomotor attention) Trails B (divided/alternating attention) Matrix Reasoning (nonverbal reasoning) RBANS (cognition) List learning Story learning Figure copy Line orientation Picture naming Semantic fluency Digit span Coding List recall List recognition Story recall Figure recall PPVT-III
18/33 104U Unable 3 13 6 19 8 4 6 2 30 1 16 0 6 Not tested
Percentile b 1st b 1st b 1st b 1st 47th 1st b 1st b 1st 1st 1st b 1st b 1st b 1st b 1st
October 24, 2005
March 23, 2006
Raw score
Percentile
Raw score
Percentile
Range
29/33 66U 377U 7
b 1st b 1st b 1st
33/33 41U 120U 12
1st b 1st b 1st
WNL Impaired Impaired Impaired
18 9 15 14 7 7 5 35 4 18 5 10 140
1st b 1st b 1st 18th b 1st b 1st 1st 1st 3rd 1st 1st 2nd 9th
28 11 18 20 6 16 8 51 7 20 5 19 149
26th 1st 20th 85th b 1st 7th 7th 26th 39th 61st 1st 84th 14th
Average Impaired Low Average Low Average Impaired Borderline Borderline Average Average Average Impaired High Average Low Average
RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; WNL, Within Normal Limits; PPVT-III, Peabody Picture Vocabulary Test, Third Version.
R.R. Cummings et al. / General Hospital Psychiatry 29 (2007) 267 – 269
Hashimoto’s encephalopathy had been established, during the second hospitalization after treatment with steroids and 4 months after the initial hospitalization when steroid treatment had been tapered. The first testing revealed global cognitive impairment with deficits including overall mental status; simple and complex attention; nonverbal reasoning; line orientation and list, story and figure learning and recall (see Table 1). During the second hospitalization, the patient showed improvements in mental status [29/33 compared to 18/33 using Cognitive Abilities Screening Instrument, Short Version (CASI-S)], line orientation (from 1st to 18th percentile) and list recall (from b 1st to 3rd percentile). In testing at 4-month follow-up, the patient showed further improvement in mental status (33/33 compared to 18/33 using CASI-S), line orientation (from 1st to 85th percentile), list recall (from 1st to 39th percentile) and also began to show improvements in list learning (from 1st to 26th percentile), coding (from 1st to 26th percentile), list recognition (from 1st to 61st percentile) and figure recall (from 1st to 84th percentile). 3. Discussion Hashimoto’s encephalopathy is a rare neuropsychiatric syndrome, the precise diagnostic and pathophysiologic characterization of which remains elusive [1,3], although it appears to involve impaired consciousness, lack of CSF evidence of bacterial or viral infection and a high serum concentration of antithyroid antibodies. As this case demonstrates, there are both neurologic and psychiatric symptoms along with considerable overlap with other disorders. In addition to diagnostic difficulties, questions
269
about treatment, including how long to treat with iv steroids, when to switch to oral steroids, how long the entire course of treatment should last and how gradual the taper should be, remain largely unanswered. Treatment is often guided by clinical status, such as nursing reports of agitation, frequency of use of bas-neededQ emergency medications and decrease in reports of hallucinations; however, as this case illustrates, behavior and psychosis may remit while cognitive deficits remain. A case by Jacob and Rajabally [4] showed that the patient’s gross clinical improvement failed to be a reliable marker of when and how to taper or discontinue the steroid course. In our case, despite the clinical improvement of the patient, there were objective cognitive deficits identified by neuropsychological testing that signaled the need for continued steroid treatment. We propose use of this testing to guide diagnosis and decisions of management. It is also possible that wider neuropsychological testing in these cases will illuminate a consistent pattern of deficits specifically enough that they may be added to diagnostic criteria.
References [1] Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth? Arch Neurol 2003;60:164 – 71. [2] Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet 1966;2:512 – 4. [3] Fatourechi V. Hashimoto’s encephalopathy: myth or reality? An endocrinologist’s perspective. Best Pract Res Clin Endocrinol Metab 2005;19:53 – 66. [4] Jacob S, Rajabally YA. Hashimoto’s encephalopathy: steroid resistance and response to intravenous immunoglobulins. J Neurol Neurosurg Psychiatry 2005;76:455 – 6.
Case Reports
Hashimoto’s encephalopathy: a case report with neuropsychological testing Ronnie R. Cummings, M.D., Steven C. Bagley, M.S., M.D.4, Saba Syed, M.D., Natalie Dong, Ph.D., Alex Lin, M.D. Department of Psychiatry, 6D-129, Olive View — UCLA Medical Center, Sylmar, CA 91342, USA Received 22 September 2006; accepted 2 January 2007
Abstract We report a case of Hashimoto’s encephalopathy with detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the deficits and their response to treatment. It highlights that behavioral and psychotic symptoms remit before cognitive deficits and suggests that the latter may be more appropriate for guiding the duration of steroid treatment. D 2007 Elsevier Inc. All rights reserved. Keywords: Hashimoto’s encephalopathy; Steroid responsive psychosis; Neuropsychological testing
1. Introduction Hashimoto’s encephalopathy is a rare syndrome characterized by altered mental status, positive antithyroid antibodies and clinical response to glucocorticoid therapy [1]. The first recognized case appeared in a 1966 report by Brain, Jellinek and Ball, who described a patient with seizures, disorientation, stroke-like episodes and fluctuating hemiparesis, along with increased cerebrospinal fluid (CSF) protein, transient electroencephalogram (EEG) abnormalities, clinical hypothyroidism and positive antithyroid antibodies [2]. There is still controversy over the association with thyroid dysfunction and the role of autoimmune antibodies, although it is generally believed to be responsive to steroid therapy [3]. The associated neuropsychiatric symptoms are diverse and can include focal neurologic deficits, seizures, confusion, disorientation and psychosis; however, the varied nature and wide spectrum of these symptoms, which overlap considerably with other psychiatric and neurologic disorders, complicates the proper diagnosis. We report here a case in which we were fortunate to acquire detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the
4 Corresponding author. Tel.: +1 818 364 4778; fax: +1 818 364 3554. E-mail address: [email protected] (S.C. Bagley). 0163-8343/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2007.01.003
deficits and their response to treatment. This case also highlights the difficulties in establishing the diagnosis.
2. Case presentation A 19-year-old Hispanic male with no prior neuropsychiatric history presented to a community hospital with confusion, disorientation, agitation and blank staring spells lasting for several minutes that had begun approximately 1 month earlier. During that brief hospitalization, he was diagnosed with absence seizures and aseptic meningitis (despite normal lumbar puncture results) and discharged on a course of phenytoin, depakote and acyclovir. Two weeks later, his family took him to a different community hospital with agitated and combative behavior; he was admitted to the psychiatric unit, treated with an unknown bsedatingQ medication and later signed out by his family against medical advice. After discharge, the patient continued on phenytoin and depakote. Three weeks later, his family brought him to our facility; the patient was still experiencing the staring spells, confusion, disorientation to place and date and agitation leading to physical conflicts with family members. The family reported that the patient had a normal developmental history. Prior to the onset of symptoms, he had been enrolled in community college and was running a small business on the Internet. There was no known prior treatment for any psychiatric disorder, recent head trauma,
268
R.R. Cummings et al. / General Hospital Psychiatry 29 (2007) 267 – 269
substance abuse, foreign travel, or infection. A distant cousin had schizophrenia. There were no abnormalities on physical examination. The neurologic exam revealed hyperreflexia in the lower extremities with myoclonus, slowed rapid alternating movements and mildly ataxic gait. The Folstein Mini-Mental State Exam score was 23 out of 30; he was oriented to person and part of the location (the state) but could not name the city, county, date, day of week, month, or year. He could not answer direct questions about mood; his affect fluctuated, and his thought process was notable for disorganization and perseveration on the name of his Internet business. The complete blood count showed mild anemia (hemoglobin = 12 g/dl). The TSH was normal (1.85 AIU/ml). Initial basic chemistry, Rapid Plasma Reagin (RPR), B12, coagulation studies, serum heavy metals (mercury, arsenic, lead), HIV, ammonia level, Antinuclear Antibodies (ANA) titer, lumbar puncture and deep punch biopsy for Lafora’s disease were all within normal limits. An ophthalmologic exam showed no Keyser–Fleischer rings. Head computed tomography and magnetic resonance imaging were also normal. EEG was performed and showed no epileptiform changes, although the patient had one observed episode of staring and drooling and, later, a tonic–clonic seizure, treated first with divalproex, changed to zonisamide because of rising serum transaminase levels. The patient expressed delusional beliefs, thinking that he was God and controlled everything, and was agitated, with flailing and yelling, requiring the use of physical restraints and haloperidol. By the end of the hospitalization, the patient’s agitation had decreased, and he was discharged to home with a prescription for zonisamide. Neuropsychological testing obtained during this hospitalization will be discussed below.
Five days later, the patient’s family brought him back to our facility because he had attacked his mother. Antimicrosomal thyroid antibodies had been sent during the previous hospitalization; those results were noted to be positive at 17.0 U/ml (reference range: b 0.5 U/ml), although the antithyroglobulin antibody test was normal. The patient was diagnosed with Hashimoto’s encephalopathy and treated with iv solumedrol 500 mg daily (later changed to oral prednisone) and olanzapine up to 5 mg twice daily for agitation. The patient’s cognition and behavior improved, and by discharge, he was able to participate in normal, spontaneous conversation; he had not needed medication for agitation during the previous 3 days, and he was discharged to the care of his family. An outpatient EEG shortly after discharge showed moderate 4–6 Hz diffuse slowing and intermittent 1–2 Hz slowing in the bilateral frontotemporal areas. At discharge, the patient was taking prednisone 60 mg/ day and zonisamide 300 mg at night. The prednisone was tapered to 40 mg at 3 weeks, at which point, his behavior was stable; he was grossly oriented, but not back in school, nor had his behavior returned to baseline. At 6 weeks, his prednisone was at 20 mg per day; he was noted to be oriented, his behavior stable, and his conversation was bcoherent and substantial.Q Five months and 3 weeks after discharge, he was again seen. He had been off prednisone for 2 weeks; he was bback to baseline in behavior and intellectQ according to his family and was again running his Internet business; the zonegran dose was lowered to 200 mg at night. He did not return later phone calls to schedule further testing. We were able to perform neuropsychological testing during the first hospitalization before the diagnosis of
Table 1 Summary of neuropsychological test results for patient with Hashimoto’s encephalopathy Test
Date of testing October 4, 2005 Raw score
CASI-S (mental status) Trails A (simple visuomotor attention) Trails B (divided/alternating attention) Matrix Reasoning (nonverbal reasoning) RBANS (cognition) List learning Story learning Figure copy Line orientation Picture naming Semantic fluency Digit span Coding List recall List recognition Story recall Figure recall PPVT-III
18/33 104U Unable 3 13 6 19 8 4 6 2 30 1 16 0 6 Not tested
Percentile b 1st b 1st b 1st b 1st 47th 1st b 1st b 1st 1st 1st b 1st b 1st b 1st b 1st
October 24, 2005
March 23, 2006
Raw score
Percentile
Raw score
Percentile
Range
29/33 66U 377U 7
b 1st b 1st b 1st
33/33 41U 120U 12
1st b 1st b 1st
WNL Impaired Impaired Impaired
18 9 15 14 7 7 5 35 4 18 5 10 140
1st b 1st b 1st 18th b 1st b 1st 1st 1st 3rd 1st 1st 2nd 9th
28 11 18 20 6 16 8 51 7 20 5 19 149
26th 1st 20th 85th b 1st 7th 7th 26th 39th 61st 1st 84th 14th
Average Impaired Low Average Low Average Impaired Borderline Borderline Average Average Average Impaired High Average Low Average
RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; WNL, Within Normal Limits; PPVT-III, Peabody Picture Vocabulary Test, Third Version.
R.R. Cummings et al. / General Hospital Psychiatry 29 (2007) 267 – 269
Hashimoto’s encephalopathy had been established, during the second hospitalization after treatment with steroids and 4 months after the initial hospitalization when steroid treatment had been tapered. The first testing revealed global cognitive impairment with deficits including overall mental status; simple and complex attention; nonverbal reasoning; line orientation and list, story and figure learning and recall (see Table 1). During the second hospitalization, the patient showed improvements in mental status [29/33 compared to 18/33 using Cognitive Abilities Screening Instrument, Short Version (CASI-S)], line orientation (from 1st to 18th percentile) and list recall (from b 1st to 3rd percentile). In testing at 4-month follow-up, the patient showed further improvement in mental status (33/33 compared to 18/33 using CASI-S), line orientation (from 1st to 85th percentile), list recall (from 1st to 39th percentile) and also began to show improvements in list learning (from 1st to 26th percentile), coding (from 1st to 26th percentile), list recognition (from 1st to 61st percentile) and figure recall (from 1st to 84th percentile). 3. Discussion Hashimoto’s encephalopathy is a rare neuropsychiatric syndrome, the precise diagnostic and pathophysiologic characterization of which remains elusive [1,3], although it appears to involve impaired consciousness, lack of CSF evidence of bacterial or viral infection and a high serum concentration of antithyroid antibodies. As this case demonstrates, there are both neurologic and psychiatric symptoms along with considerable overlap with other disorders. In addition to diagnostic difficulties, questions
269
about treatment, including how long to treat with iv steroids, when to switch to oral steroids, how long the entire course of treatment should last and how gradual the taper should be, remain largely unanswered. Treatment is often guided by clinical status, such as nursing reports of agitation, frequency of use of bas-neededQ emergency medications and decrease in reports of hallucinations; however, as this case illustrates, behavior and psychosis may remit while cognitive deficits remain. A case by Jacob and Rajabally [4] showed that the patient’s gross clinical improvement failed to be a reliable marker of when and how to taper or discontinue the steroid course. In our case, despite the clinical improvement of the patient, there were objective cognitive deficits identified by neuropsychological testing that signaled the need for continued steroid treatment. We propose use of this testing to guide diagnosis and decisions of management. It is also possible that wider neuropsychological testing in these cases will illuminate a consistent pattern of deficits specifically enough that they may be added to diagnostic criteria.
References [1] Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth? Arch Neurol 2003;60:164 – 71. [2] Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet 1966;2:512 – 4. [3] Fatourechi V. Hashimoto’s encephalopathy: myth or reality? An endocrinologist’s perspective. Best Pract Res Clin Endocrinol Metab 2005;19:53 – 66. [4] Jacob S, Rajabally YA. Hashimoto’s encephalopathy: steroid resistance and response to intravenous immunoglobulins. J Neurol Neurosurg Psychiatry 2005;76:455 – 6.