Clinical Reasoning: A 59-Year-Old Man With Thymoma and Constitutional Symptoms, Seizures, and Multifocal CNS Lesions.

A 59-year-old man first presented for an episode of left arm numbness. During workup, a thymoma was incidentally discovered and resected. The symptoms in his left arm were attributed to a cardiac pathology. One month later, he began to experience fatigue, weight loss, and anorexia, followed by one generalized tonic-clonic seizure. Workup including toxic and metabolic screening and MRI Brain were unremarkable. He was started on an anti-seizure medication and did well for two years, when his symptoms recurred. Repeat MRI Brain showed multiple cortical T2/FLAIR hyperintense lesions without enhancement or diffusion restriction. Further workup included spinal MRI, CT chest/abdomen/pelvis, CSF studies, autoimmune/paraneoplastic panels in CSF and serum, all of which were unremarkable. Serum testing was positive for striational antibodies, acetylcholine receptor (AChR) binding antibodies, and AChR modulating antibodies. He received high dose steroids and plasma exchange with resolution of his symptoms, and has since been stable on mycophenolate mofetil. This presentation highlights the rare association between thymoma and encephalitis. Prompt identification and treatment is critical. This article discusses the diagnostic approach to this rare presentation including essential features of the clinical presentation, appropriate workup, pertinent differential diagnoses, and key points for the treatment of these patients.

Refractory Anti-NMDA Receptor Encephalitis in Early Pregnancy: A Case Report of Treatment Course and Pregnancy Outcomes.

BACKGROUND AND OBJECTIVES: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis classically affects women of childbearing age, producing a disproportionate number of pregnant women with anti-NMDAR encephalitis. The typical presentation includes progressive neuropsychiatric symptoms, seizures, and alterations in consciousness, all of which present potential risks to the fetus. First-line and second-line treatments similarly pose teratogenic potential; therefore, randomized studies with supportive data on pregnancy and fetal outcomes are lacking. METHODS: We present a case of refractory anti-NMDAR encephalitis during the first and second trimesters of pregnancy with the successful use of rituximab and cyclophosphamide and resultant healthy pregnancy. RESULTS: The patient was treated with an escalating immunotherapy regimen from 11 to 15 weeks of gestation, including steroids, plasma exchange, IV immunoglobulins, and rituximab, with no clinical response. At 16 weeks of gestation, she received cyclophosphamide with clinical improvement after 4 weeks. She subsequently gave birth to a healthy, term baby boy, who continued to do well at the follow-up. DISCUSSION: This case illustrates the effective use of cyclophosphamide in the second trimester of pregnancy for anti-NMDAR encephalitis. The use of second-line therapies remains an individualized decision because the relative risk-to-benefit ratio in pregnant women is incompletely understood.

Antibody Testing for Neurological Autoimmune Disorders: Evaluation of Best Practices at a Tertiary Referral Center.

Background: Autoimmune neurology is a rapidly evolving field of study, where best practices for neurological antibody testing have yet to be determined. The growing number of options for antibody panel testing can create confusion amongst ordering clinicians and lead to ordering several concurrent panels (i.e., overlapping evaluations) or repeat panel evaluations. This study determined the frequency of these evaluations for autoimmune and paraneoplastic disorders and investigated how these practices informed clinical decision making and management. Methods: This was a retrospective observational study of adult patients presenting to University of Texas Southwestern (UTSW) in 2017 with requests for antibody panels for autoimmune encephalitis and paraneoplastic disorders. Individuals with more than one panel requested were defined as either an overlapping evaluation (more than one panel requested within 14 days) or repeat evaluation (more than one panel requested 14 or more days apart). For those individuals with repeat panel testing, the proportion of panels with a change in antibody status or subsequent changes in clinical diagnosis and decision making were recorded. Results: There was a total of 813 panels sent on 626 individuals. Twenty percent (126 individuals) had more than one panel requested. Only 10% of individuals had a matched serum and CSF evaluation. Forty-seven overlapping evaluations were performed in 46 (7.3%) of the individuals studied. Fifty-four (8.6%) individuals underwent 70 repeat evaluations encompassing 79 panels (9.7% of total panels ordered). Ten repeat evaluations showed a change in antibody status, of which only two were clinically significant. There was a single case where clinical management was affected by repeat autoantibody evaluation. Conclusions: Ordering practices for suspected autoimmune encephalitis and paraneoplastic disorders are suboptimal with frequent overlapping antibody panel evaluations and non-paired serum/CSF samples at our center. Repeat autoantibody testing is a commonplace practice yet yielded novel information in only a minority of cases. These new results were, as a rule, clinically irrelevant and changed clinical decision making in <1% of cases. There is limited utility in these practice patterns. Future efforts should be directed at the development and standardization of neurological autoimmune and paraneoplastic autoantibody testing practice standards.

Cathodal and anodal left prefrontal tDCS and the perception of control over pain.

OBJECTIVES: The prefrontal cortex may be a promising target for the use of transcranial direct current stimulation (tDCS) in the management of pain symptoms. The present study explored the effects of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex on the effects of perceived pain controllability. MATERIALS AND METHODS: Forty-one participants received continuous anodal or cathodal tDCS and underwent a laboratory pain task designed to manipulate the perception of pain control. Participants were told that they would be completing a reaction-time task (press keyboard button of corresponding arrow shown on computer screen with either green or red background). A thermal pain stimulus was delivered following each trial by a thermode placed on the participant's left forearm. Although pain stimuli were pseudorandomally ordered and matched for total duration between control (green) and noncontrol (red) trials, participants were told that if they responded correctly and more quickly on green trials than their average reaction times, the thermal pain stimulus duration would be decreased (ie, perceived control). Participants were told they had no control of pain stimulus duration over trials presented with the red background. RESULTS: There was a significant main effect for tDCS condition (anode vs. cathode) on pain unpleasantness ratings (P<0.04). Specifically, individuals receiving cathodal tDCS reported higher pain unpleasantness ratings (least squares mean=69.40, SE=3.72), whereas those receiving anodal tDCS reported lower pain unpleasantness ratings (least squares mean=58.05, SE=3.81). Exploratory analysis revealed a simple main effect for tDCS group at the level of perceived controllability (P<0.02). In addition, participants receiving cathodal tDCS subjectively reported feeling less control of the painful stimuli than those receiving anodal tDCS. DISCUSSION: Left dorsolateral prefrontal cortex tDCS may play a role in modulating the neurocircuitry involved with the perception of control over pain.

Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).

BACKGROUND: Although pain is often a symptom that precedes total knee arthroplasty (TKA), the procedure itself is associated with considerable postoperative pain lasting days to weeks. Postoperative pain control is an important factor in determining recovery time, hospital length of stay, and rehabilitation success. Several brain stimulation technologies including transcranial direct current stimulation (tDCS) have demonstrated promise as treatments for a variety of pain conditions. The present study examined the effects of 4 sessions of tDCS on post-TKA pain and opioid consumption. MATERIALS AND METHODS: Forty patients undergoing unilateral TKA were randomly assigned to receive a total of 80 minutes of real (n=20) or sham tDCS (n=20) with the anode over the knee representation of the motor strip (C1h or C2h corresponding to the target knee) and cathode over the right dorsolateral prefrontal cortex (F3; located by the EEG 10-20 System). Patient-controlled analgesia ( hydromorphone) use was tracked during the ∼48 hours postsurgery. RESULTS: Patients in the real tDCS group used an average of 6.6 mg (SD=5.3) of patient-controlled analgesia hydromorphone, whereas those in the sham group used 12.3 mg (SD=6.6; t37=2.93, P=0.006). Despite using less opioid medication, participants in the real tDCS group reported no pain exacerbation or worse mood with respect to those in the sham tDCS group. CONCLUSIONS: Results from this pilot feasibility study suggest that tDCS may be able to reduce post-TKA opioid requirements. Although these results are preliminary, the data support further research in the area of adjunctive cortical stimulation in the management of postsurgical pain.