A 26-year-old female patient was brought to the emergency department by her mother with reported "multiple seizures" on 9/11/2021. The mother reported that the patient was down visiting from Connecticut, where she had gone to a party alone 5 days prior, and her twin sister had felt she was acting abnormal and confused after returning from the party. The patient had gone to the ER in Connecticut and been prescribed olanzapine. The mother brought the olanzapine bottle and there were only 16 pills left when there should have been about 25, although the mother reported that a few pills had been wasted when the mother tried to give them to the patient and she spit them out. The patient had a witnessed, generalized tonic-clonic seizure in the Florida ED, and remained post-ictal the entire time in that department. She also had a very prolonged QTC on EKG. All toxicology tests were negative, but it was felt that she might be reacting to an OD of olanzapine. She was given Keppra and Ativan, and a battery of tests were run. The ED doctor's note says "LP had clear fluid was uncomplicated she did react to the pain of the LP but did not fully wake up." There is no other evidence in the records that a lumbar puncture was done on 9/11, other than an addendum from days later saying that housekeeping threw out the specimen. The patient was admitted early in the morning of 9/12, and a routine neurology consult was requested. The admitting doctor also ordered a brain MRI and vEEG, which showed a "markedly abnormal stupor/asleep state" as well as several confirmed generalized tonic-clonic seizures and postictal sharp waves in the left front-central region "with some reflection over the right side as well." The neurologist saw the patient later in the evening of 9/12, and noted that the CSF results and MRI brain were still pending, and the patient was still on empiric IV antibiotics and acyclovir. On 9/13, the patient was intubated to protect her airway. Also on 9/13, the infectious disease consulting doctor put in a new order for a lumbar puncture, but it was not completed until the following day, 9/14. The initial results from the LP were: glucose 59, protein 28, colorless, clear fluid, RBCs 565, WBCs 26, and lymphocytes 96. The MRI brain was also done 9/14 and showed no acute findings. On 9/16/2021, a critical care doctor ordered NMDA receptor autoantibody testing to be added on to the CSF that was already in the lab. Those results apparently did not come back until 9/27, and they were positive. Also, on 9/27, IV Solu-Medrol was ordered and given for the first time, and plasmapheresis was started. On 10/1, a transvaginal ultrasound was attempted to look for ovarian teratoma, but it could not be done. Only the right ovary was able to be visualized on pelvic ultrasound, and it was described as having a "dominant follicular cyst... measuring 1.8 cm in size." The patient was also given dexamethasone starting on 10/3, but no IVIG infusion or second-line therapies were given. On 10/8, the patient was transferred to a different hospital "to taper her off sedation to see if she still has seizure like activity under continuous EEG monitor before starting rituximab." At the second hospital, the patient was diagnosed with a right ovarian teratoma, 2.3 cm in size, and underwent an oophorectomy on 10/12. She had a long, complicated hospital course which included treatment with IVIG, rituximab, tenofovir (for positive Hep B antibodies), and eventually multiple courses of ECT for catatonia. In June of 2022, she was finally able to be discharged home with her mother.
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Do you believe there might have been medical error?
This patient seems to likely have met criteria for probable anti-NMDA receptor encephalitis as proposed by Graus et al. in Lancet Neurology in 2016 and should have been treated accordingly. A lumbar puncture was performed on 9/11 per some documentation but the test results were not run as they were apparently thrown out. This should never happen as it required the patient to undergo a second lumbar puncture, which was then delayed all the way until 9/14. After initial clinical and EEG results showed several generalized seizures, the patient should have been transferred to a facility that had continuous EEG capabilities in order to adequately manage this patient. In the absence of that, it is possible that the patient continued to have nonconvulsive seizure activity that went unrecognized for many days after the initial testing, which can lead to further brain injury. This patient may have met criteria for NORSE (new onset refractory status epilepticus) which warrants more aggressive treatment initially. With ongoing seizures and altered mental status and spinal fluid showing no evidence of CNS infection, the diagnosis should have been presumed autoimmune encephalitis and she should have been started on treatment as soon as CSF showed no evidence of infection, likely on 9/16. Instead, any immunosuppressive therapy was delayed more than 10 days until 9/27. A transvaginal ultrasound or other imaging could have been done to look for malignancy much earlier than 10/1, 4 days after the NMDA-receptor antibody came back. In fact, many clinicians with experience in managing such cases would have looked for malignancy prior to the NMDA-receptor antibody returning positive, and best practice recommendations note this strategy. Then, when the ultrasound could not visualize the ovaries well enough, an MRI of the pelvis could have been done instead but was not. It is not clear to me why she was given dexamethasone on 10/3 as she should already have been receiving high dose solumedrol, and if she hadn't responded to steroids at that point then treatment with IVIG or plasmapheresis would have been appropriate. They eventually transferred her to a hospital with continuous EEG on 10/8, nearly a month after initial presentation. Within days of arrival they had removed her ovarian teratoma, the main important treatment for NMDA-receptor antibody encephalitis in patients in whom a teratoma is found.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
The lack of continuous EEG monitoring at the initial hospital makes it highly likely that she continued to have nonconvulsive seizures there and that they went untreated, leading to further brain injury. She should have been transferred to a center with continuous EEG capabilities much earlier. The very long delay in treatment of autoimmune encephalitis due to waiting until the test result came back positive led to the brain inflammation having more time to cause brain injury. The long delay in diagnosing an ovarian teratoma also caused more time for the inflammation to cause brain injury. Ultimately the treatment provided with only steroids was insufficient. Studies suggest that early and aggressive immunotherapy is associated with improved outcomes in autoimmune encephalitis.
What makes you a good expert for this case?
I am board-certified neurologist and neurointensivist with 10+ years of experience in both academic and community medical centers. I have extensive experience in acute diagnosis and management of NMDA-receptor antibody encephalitis as well as other autoimmune encephalitides and new-onset refractory status epilepticus in general.
How often do you encounter cases similar to this one in your practice?
Although these are rare cases, I have managed similar cases of new-onset refractory status epilepticus 3-4 times per year for the past 10+ years.
Do you believe there might have been medical error?
Based on the information provided, I am uncertain. Typically patients with NMDA encephalitis have psychiatric manifestations, though this patient had a prior psych history making that difficulty to interpret; they also present with seizures, decreased level of consciousness, and movement disorder. Often the diagnosis takes time yet there are clues that make the diagnosis more likely such as the EEG and MRI.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
Again, there is too little information to provide an opinion at this time; however, earlier treatment typically improves the outcome.
What makes you a good expert for this case?
I am a board certified neurologist and neurocritical care physician at an academic medical center. I have taken care of 10s of patients with NDMA encephalitis and many more with other forms of autoimmune encephalitis. I have authored over 100 peer reviewed articles on neurological diseases. I have served as an expert on several prior cases and have provided live trial/deposition testimony for both the defense and plaintiff. Please see my CV for further information.
How often do you encounter cases similar to this one in your practice?
I have taken care of 10s of patients with NDMA encephalitis and many more with other forms of autoimmune encephalitis.
Do you believe there might have been medical error?
There are a few issues surrounding this case based on the presentation: 1. It says that house-keeping threw away the sample. There is no mention that the ED physician looked for the sample or performed it again due to a hospital error. The sample was lost and could've provided initial clues to inflammation. 2. The second LP was done done until 3 days later. This should've been prioritized. Since anti-NMDA antibody tests have a longer than usual turn around time, this led to delay in diagnosis and treatment. 3. The ultrasound was not completed and should've been repeated since a diagnosis of a paraneoplastic process could've been expedited.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
It does not appear that a medical treatment or test directly led to an injury. There were delays in management and a chart review may be needed to assess causation.
What makes you a good expert for this case?
I have several years of experience in reviewing medico-legal cases, especially those related to acute care neurology. I have reviewed thousands of pages of medical records and am comfortable combing through all types of documentation including nursing, physician and pharmacy notes.
How often do you encounter cases similar to this one in your practice?
My primary work place is in a busy neuro-critical care unit and I have taken care of hundreds of patients with seizures and status epilepticus (as described in this case). Although rare, I am trained to send for anti-NMDA testing in a patient with seizures, especially if the case is similar to the one presented above. I have taken care of several patient's with anti-NMDA encephalitis.
Do you believe there might have been medical error?
The patient had multiple confounders and potential reasons to present with status. The fact that the utox was negative does not indicate much since olanzapine would not have been detected on utox. The delay in treatment with steroids is due to the fact that the NMDAR Abs would easily take 7-10 days to result. It seems they did suspect it hence it was sent. It is not unreasonable to start with dexamethasone and to see if she responds before she is started on a second-line agent that tends to be more invasive.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
Sadly samples can be lost occasionally. It is especially frustrating when we are dealing with precious samples like CSF. There is no reason to assume the MD incorrectly documented an LP procedure in a young patient where an LP is definitely indicated. It is unclear from this summary if the patient as on continuous video EEG? How was the status managed?
What makes you a good expert for this case?
I treat autoimmune encephalitides routinely. As a neurointensivist practicing in a Quaternary care center, I would have at least 1-2 patients with NMDA receptor encephalitis or other encephalitides a month.
How often do you encounter cases similar to this one in your practice?
I treat autoimmune encephalitides routinely. As a neurointensivist practicing in a Quaternary care center, I would have at least 1-2 patients with NMDA receptor encephalitis or other encephalitides a month.
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