|Year : 2020 | Volume
| Issue : 1 | Page : 22-27
A combined behavioral and pharmacological approach in nonparaneoplastic-related anti-N-methyl-D-aspartate receptor encephalitis: A case report with positive outcome in a male patient
Matthew Rong Jie Tay, Karen Sui Geok Chua
Department of Rehabilitation Medicine, Tan Tock Seng Hospital, Singapore
|Date of Submission||02-Sep-2019|
|Date of Decision||21-Jan-2020|
|Date of Acceptance||10-Feb-2020|
|Date of Web Publication||31-Mar-2020|
Dr. Matthew Rong Jie Tay
Tan Tock Seng Hospital Rehabilitation Center, 17 Ang Mo Kio Ave. 9, 569766
Source of Support: None, Conflict of Interest: None
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare but potentially life-threatening and disabling autoimmune encephalitis mainly affecting young women. We report the case of a male in his early thirties who developed behavioral and neurocognitive manifestations of anti-NMDAR encephalitis. This case highlights the unique behavioral challenges in a male patient during the course of rehabilitation, including impulsivity, inappropriate sexual behavior, and hyperphagia, which has not been well-described in the literature. This presented complex problems for the rehabilitation team and amelioration of these clinical issues required a multidisciplinary approach. The behavioral and pharmacological strategies employed, which had a pronounced positive contribution in this patient, are described. A brief review of the epidemiology, course, and common complications of anti-NMDAR encephalitis is also presented.
Keywords: Anti-N-methyl-D-aspartate receptor encephalitis, cognitive disorders, neuropsychology, sexuality
|How to cite this article:|
Tay MR, Chua KS. A combined behavioral and pharmacological approach in nonparaneoplastic-related anti-N-methyl-D-aspartate receptor encephalitis: A case report with positive outcome in a male patient. J Int Soc Phys Rehabil Med 2020;3:22-7
|How to cite this URL:|
Tay MR, Chua KS. A combined behavioral and pharmacological approach in nonparaneoplastic-related anti-N-methyl-D-aspartate receptor encephalitis: A case report with positive outcome in a male patient. J Int Soc Phys Rehabil Med [serial online] 2020 [cited 2022 Aug 10];3:22-7. Available from: https://www.jisprm.org/text.asp?2020/3/1/22/281632
| Introduction|| |
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune encephalitisfirst described in 2007, with a reported prevalence of 1.5/million population/year. Approximately 80% of patients with anti-NMDAR encephalitis are women, with the frequency of an underlying teratoma infemale patients older than 12 years old being more than 50%. In cases where a teratoma is identified, tumor removal can be curative, along with adjunctive immunotherapy. However, as only 5% of male patients have an underlying tumor, treatment is usually through nonsurgical means, including early immunosuppressive therapy.
The clinical course often starts with a transient prodromal viral phase. Subsequently, the patient enters a psychotic phase in the early weeks of the disorder, characterized by delusions, agitation, and confusion, which can often be mistaken as a primary psychotic disorder. This is followed by neurological complications, including seizures, movement abnormalities, hypoventilation, and significant autonomic instability, which often necessitates intensive care. With early and aggressive therapies, most patients recover, although cognitive and behavioral deficits may persist for several months or even years.
A large case series wasfirst described in 2008 by Dalmau et al., who characterized the clinical course as above. Subsequent case reports have focused on the medical challenges of such patients, including the need for early recognition of the disorder, nursing care in the intensive care setting, coordination of care between the psychiatry, neurology, and internal medicine services in managing the psychiatric and neurologic complications of this disorder, and the management of female patients with teratomas., Fewer case reports have focused on the behavioral and cognitive challenges, rehabilitation strategies, and functional outcomes in patients with anti-NMDAR encephalitis.,,, Most of these studies mention the use of psychotropic medications to treat neuropsychiatric symptoms., Many patients in these case studies also receive cognitive rehabilitation, although cognitive function may require months to years to recover., Case reports have also described hypersexuality in female patients,, although discussion of this complication in male patients is limited in the literature. In addition, predicting functional outcomes can be difficult, although it has recently been shown that prerehabilitation prognostic factors can portend poor functional status at 1 year. This case study illustrates the unique rehabilitation challenges of this illness in the postacute phase of a male patient, including inappropriate sexual behavior (ISB) and impulsivity, and the positive functional outcomes achieved through a combination of behavioral and pharmacological interventions in nonparaneoplastic anti-NMDAR encephalitis.
| Case Report|| |
A middle-aged previously healthy male in his thirties with no recent travel historyfirst presented to a specialized neurological unit with fever, confusion, and myoclonic jerks. His condition rapidly deteriorated as he developed progressive encephalopathy, multiple seizures, and respiratory failure from central hypoventilation. This required a transfer to the intensive care unit. Magnetic resonance imaging (MRI) of the brain revealed fluid-attenuated inversion recovery signal abnormalities and parenchymal contrast enhancement in the right temporal region; electroencephalogram (EEG) demonstrated continuous slow activity suggestive of severe diffuse encephalopathy; and cerebrospinal fluid (CSF) revealed an elevated protein level of 91 mg/dL without pleocytosis Based on the clinical presentation and EEG findings, a probable diagnosis of anti-NMDAR encephalitis was made, which was subsequently confirmed based on positive serum and CSF anti-NMDAR antibodies. A workup for malignancy was negative. He was treated with intravenous immunoglobulin 2 g/kg, followed by oral prednisolone 1 mg/kg q.d. He had a 1-month stay in intensive care due to a protracted recovery course and prolonged intubation requiring tracheostomy creation. Multiple antiepileptics (phenytoin, gabapentin, levetiracetam, and lorazepam) were needed for intractable seizures and myoclonus control.
He was then transferred to a general ward for another 2 months after ventilator weaning was achieved. Physiotherapy and occupational therapy were then initiated with regular chest physiotherapy, and decannulation was successful. He was initially severely deconditioned (global power of 3 in all extremities), requiring maximal assistance in bed mobility and all his basic activities of daily living (ADLs). Upon discharge from the general ward, his function had gradually improved such that he was independent in bed mobility and required only standby assistance in his basic ADLs. No behavioral abnormalities were reported during acute hospitalization. He was then transferred to an inpatient neurological rehabilitation unit. He did not have any focal motor neurological deficits with intact visual fields and pupillary reflexes. He had severe deconditioning with a weight loss of 13.8 kg compared to premorbid weight and a body mass index of 14.9.
Mild cognitive deficits (Montreal Cognitive Assessment [MOCA] score 25/30) were noted, with impairments in the domains of visuospatial (3/5), language (2/3), orientation (5/6), and memory function (4/5). Behavioral abnormalities such as impulsivity, social inappropriateness, ISB (e.g., suggestive language and hugging female health-care workers), rudeness, and verbal abusiveness (e.g., using vulgarities, provoking other patients verbally, and lack of table manners) were noted during admission for inpatient rehabilitation, which were not present during his initial acute hospitalization stay. Hyperphagia, impaired sleep initiation, and anxiety were also observed. The general principles of acquired brain injury cognitive rehabilitation were employed, using individualized behavioral analyses and modification along with patient-centric goals. His inpatient rehabilitation management is summarized in [Table 1].
Given his mild cognitive deficits, cognitive-behavioral techniques were deemed appropriate to address the patient's ISB and impulsivity. These focused on reeducation of social norms and exploration of the intentions behind each behavior to address cognitive distortions. The rehabilitation psychologist worked with the patient to explicitly highlight abnormal thoughts and behaviors (e.g., grabbing health-care workers' lanyards to view their photos, hugging the occupational therapist during dressing training, and commenting on the physical appearance of health-care workers), reflect on the inappropriateness of such behavior (e.g., causing distress to others and possibility of inappropriately touching the body parts), and in problem-solving (e.g., asking for the names of health-care workers, asking permission before holding onto someone for support, making general pleasantries instead of comments of a sexualized nature). The occupational therapist required a high degree of physical contact for ADL training in the initial phases, and hence, a male occupational therapist was reassigned to the patient for safety reasons. As the patient's ISB was inadequately controlled with behavior management strategies within the 1st week, pharmacological therapy was deemed necessary. Extrapolating from existing ISB treatment guidelines for patients with dementia, cimetidine 200 mg b.i.d. and finasteride 1 mg q.d. were trialed with success. These agents were chosen as the patient was already on escitalopram 20 mg q.d. for anxiety. A reduced incidence of ISB was reported by his family and the rehabilitation team within 2 weeks. As his ISB improved, a sexual counselor also advised on appropriate levels of intimacy in public (e.g., touching hands, elbows, and shoulders and kissing on cheeks only) and to seek his wife's consent before displaying such behaviors. His wife was also counseled to set appropriate boundaries to avoid unnecessary distress on her part.
The patient also exhibited periods of impulsivity, such as yelling multiple times at a therapist when he was frustrated. These episodes often resolved with nonconfrontational language and verbal de-escalation techniques, although more serious physical or verbal aggression necessitated a time-out intervention. These episodes were then used by rehabilitation therapists to discuss the consequences of such actions with the patient (e.g., missing therapy sessions which resulted in a delayed discharge) and to draft a written contract stating socially appropriate or inappropriate behavior and the associated repercussions. Specific verbal praises were used to reinforce appropriate behaviors. The speech therapist reviewed him daily for one-on-one simulated conversations, and he was able to progress to a group therapy format with other patients, and eventually to a supervised real-world community outing where he had opportunities to interact with strangers.
Hyperphagia was noted as the patient would snack frequently in between meals and over-order food at the hospital cafeteria. This was complicated by the fact that the patient had severe wasting after a prolonged hospitalization stay. A workup for organic causes was negative, and the patient was not receiving any appetite stimulants such as prednisolone. A nutritionist reviewed his dietary intake and estimated energy expenditure weekly. Although his dietary requirements allowed for a net positive weight gain, the dietary review showed that he was taking 20% above his estimated energy requirements. The nutritionist recommended an appropriate food menu with nutritional supplements in lieu of snacks. Mindful eating techniques were utilized in consultation with the psychologist (e.g., consuming small portions, eating slowly, chewing thoroughly, and stopping when full). Negotiation techniques were taught to his family members, such as reaching an agreement with the patient to order only 1 main course and 1 drinkfirst before ordering more food. To avoid stimulus-bound behavior, food items were removed from his hospital cubicle, and his family members avoided bringing him near the cafeteria. The use of escitalopram in the patient may have indirectly contributed to a better appetite (through the treatment of anxiety), although a medical decision was made to continue with the drug. These strategies enabled a safe weight gain of 3.8 kg upon discharge from rehabilitation.
The patient demonstrated anxiety, especially when confronted with unfamiliar environments or people, and was highly reliant on his wife's presence to overcome his fear of unfamiliarity. In addition to the use of escitalopram, a graded behavioral exposure strategy was employed, with the patient progressing from one-on-one therapy in his hospital cubicle, to one-on-on therapy in rehabilitation gym, to group therapy as tolerated, and his wife was concurrently instructed to gradually reduce the amount of time spent with him. Familiar items such as photos and books were placed in the patient's room, and relaxing events of the patient's choice (e.g., watching comedy) were scheduled along with fixed therapy timings. The patient was taught to use deep breathing techniques by the psychologist when he was confronted with stressful situations. Staff members and especially those new to the patient were instructed to introduce themselves, explain the purpose of their interaction and ask for permission from the patient before performing any procedures or action.
To enhance attention training, it was essential to use techniques such as task redirection, repetition, visual cueing, and maintaining a quiet, clutter-free area for task-specific training. Compensatory memory strategies were used. For example, an orientation book was provided with his medical details, therapists, daily schedule, and calendar to address memory deficits and provide temporal orientation. Topographic orientation was reinforced to the patient during transfer to and from the rehabilitation gym. These allowed the patient to tolerate a higher intensity of engagement and participation. These techniques were also incorporated into functional skill training with daily physiotherapy, occupational, and speech therapy sessions. Balance exercises progressed from heel-to-toe walking to wobble board training, and treadmill walking was utilized to improved walking endurance.
Weekly interdisciplinary team meetings were held to ensure intra-team consistency with behavior management strategies and to review his rehabilitation progress. When required, daily team huddles were organized to highlight incidents by members of the rehabilitation team (nurses, therapists, physicians, medical social workers, and psychologists). This enabled daily rehabilitation progress or deterioration to be ascertained when required, and allowed strategies to be discussed and enforced at a team level. The patient's family members were also taught the same strategies as the rehabilitation team to ensure consistency and were also given self-care advice. Progress was determined during team meetings based on qualitative feedback from the team and the family members, achievement of weekly goals (e.g., progressing from one-on-one therapy to group therapy), and the use of functional measures (e.g., MOCA, Berg Balance Scale, and Functional Independence Measure [FIM] scores).
The patient was discharged home after 1 month of inpatient rehabilitation. He was able to perform most basic ADLs with complete independence and was able to interact appropriately more than 50% of the time. This was in contrast to his initial rehabilitation assessment where he required supervision for most ADLs and was either withdrawn or verbally inappropriately most of the time. This was reflected in an improvement in FIM score from 80 (motor scores 73, cognitive score 7) to 93 (motor score 76, cognitive score 17). Finasteride and cimetidine were discontinued
3 months postdischarge, and escitalopram was weaned off. There was no further ISB. His wife gauged that the overall level of social inappropriateness had improved significantly such that she no longer required to use previously taught techniques (e.g., verbal de-escalation and time-out intervention). A repeat MOCA at 4 months postonset improved to 28/30, with deficits in attention (5/6) and language (2/3). Antiepileptics were tailed off at 1 year, and there was no seizure recurrence after antiepileptic drugs were weaned off. A neuropsychiatric assessment performed at 1 year postillness revealed intact working memory, visuospatial construction skills, language ability, and learning. However, there were significant deficits in information processing speed and executive function [Table 2], which were consistent with the disease course.,, The quality of life scores with the Depression Anxiety Stress Scale-21 showed no depression or stress, although there was a moderate level of anxiety. He was able to return to his previous occupation at 2 years postillness and was coping well at the last review 3 years postillness.
| Discussion|| |
Behavioral complications were absent during the patient's acute hospitalization stay, which was probably because the patient was too cognitively and neurologically impaired during that period and was also receiving multiple potentially sedating antiepileptics. After the patient recovered both physically and cognitively, behavioral complications then manifested in the subacute rehabilitation setting, reinforcing the need for rehabilitation providers to be vigilant for such complications.
Many patients with anti-N-methyl-D-aspartate (NMDA) encephalitis often experience neuropsychiatric deficits after acute illness, which are predominantly that of attention, episodic memory, and executive control. A baseline cognitive screen such as MOCA can prove useful in delineating the affected domains, planning cognitive rehabilitation, and monitoring cognitive recovery. As our patient had only mild memory deficits, he benefited from self-monitoring and memory aids. In terms of behavioral problems, self-management and cognitive-behavioral techniques were effective. The positive response to behavior management strategies was also likely contributed by the relative preservation of his memory, as he was able to learn procedurally and had good support from his wife. Conversely, rehabilitation of a severely amnesic or highly aggressive patient may require a different approach, such as implicit learning for knowledge transmission and antecedent environmental factor manipulation together with an operant neurobehavioral approach for behavioral management. The 10 points gain in cognitive FIM compared to the modest 3-point motor FIM gain highlights the tangible benefits of behavior management strategies, which often require the presence of a behavioral psychologist and interdisciplinary teamwork in the rehabilitation milieu. Cognitive and behavior management strategies can be tailored accordingly as the patient improves. With cognitive recovery, lengthier and formal neuropsychological assessments can be performed in the subacute or chronic setting to identify and address subtle cognitive deficits for the purposes of community reintegration or vocational rehabilitation.,
This case also highlights the manifestations of ISB and its management in a rehabilitation context, which has not been well described in male patients with anti-NMDA encephalitis. Much of the evidence is based on the case reports or small case series in elderly patients with dementia. The management of ISB in a male patient starts with behavior management strategies, and pharmacological measures to reduce libido can be considered if these measures fail. Selective serotonin reuptake inhibitors are often recommended asfirst-line agents in ISB due to their good safety profile. In addition, the antiandrogens finasteride and cimetidine have been used for hypersexual behavior in elderly men with dementia, and were utilized successfully in this patient as he was already on escitalopram.
Several negative prognostic factors were identified before inpatient rehabilitation, including intensive care unit admission, lack of initial clinical improvement, presence of a movement disorder, central hypoventilation, abnormal MRI findings, and an elevated CSF protein level. Despite the presence of these factors, Balu et al. showed that 32% of such patients achieve good functional recovery at 1 year. In addition, in our patient, his young age, the relatively preserved cognition at the start of inpatient rehabilitation, an interdisciplinary team approach, pharmacotherapy (escitalopram, cimetidine, and finasteride) for neuropsychiatric complications coupled with behavioral remediation, individualized behavioral analyses and modification, early and strong family involvement, and functional progress were likely contributors to his positive outcome of family and work integration within 4 and 24 months of illness, respectively.
Despite an initially severe clinical presentation, patients with anti-NMDAR encephalitis can continue to achieve functional recovery even after 1-year postsymptom onset, and such patients may benefit from continued integrated and multidisciplinary rehabilitation. Neuropsychiatric manifestations such as ISB may pose unique challenges in a male patient and should be addressed appropriately. As long-term behavioral and cognitive sequelae may persist, continued outpatient monitoring for the emergence of new psychosocial issues, rehabilitative services, and psychosocial support for patients and their family are often warranted in the chronic phase. Therefore, such patients are likely best managed in specialized rehabilitation settings able to provide the breadth and depth of services required as well as the long-term follow-up for work reintegration.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]