Saturday, October 31, 2015

Super-refractory status epilepticus

A 13-year-old girl was admitted to the pediatric ICU at Cleveland Clinic in November 2013. At the time of her transfer from another institution, she was in an induced coma for status epilepticus. She had been evaluated here 2 years earlier as a possible candidate for epilepsy surgery; at that time, she was having five to eight seizures per day. However, her EEG and MRI results at the time had indicated bilateral brain abnormalities, so epilepsy surgery had not been an option.


This patient's neurologic symptoms dated back to age 5 years, when her parents say she began experiencing memory problems and became shy and withdrawn. At age 7 years, she began to experience episodes of nausea and abdominal pain, sometimes accompanied by visual hallucinations described as "flashes of light." These episodes were later confirmed to be seizures.

Her first grand mal seizure occurred at age 8 years, and her seizures increased in frequency as she grew older. She also had progressive unsteady gait and slurred speech due to progressive cerebellar atrophy. Through the years, she underwent extensive metabolic and genetic testing as well as brain MRI studies. The latter showed atrophy of the cerebellum and abnormal signal changes in both temporal lobes and the left occipital lobe. A small tumor was found on her adrenal gland in 2010. Because no excess hormones were detected, it was thought to be a nonfunctioning adenoma.


When the patient first arrived in the pediatric ICU, her seizures were stopped by induced coma, but the seizures returned when we attempted to wean her from the drugs.

We revisited the primary etiology of her illness. The cerebrospinal fluid (CSF) showed nonspecific signs of inflammation (raised oligoclonal bands and neopterins). The size of the adrenal tumor (1.5 cm × 2.5 cm) was unchanged since its discovery 3 years earlier. The commercially available panel of testing for autoantibodies in CSF was negative. However, the laboratory at her prior institution had noted the presence of anti-Purkinje cell-like antibody in her serum and CSF. This antibody is novel and not yet further characterized. We came to suspect the tumor as the source of both her neurologic and gastrointestinal symptoms.

Our first attempt to remove the tumor was unsuccessful, as she was unstable. But a second attempt succeeded 6 weeks after her admission to the hospital. We started her on multiple types of immunotherapy, including plasmapheresis, methylprednisolone, intravenous immunoglobulin, rituximab, and cyclophosphamide.


Two weeks after removal of the tumor, we slowly brought the patient out of her induced coma. She became increasingly awake, and the frequency of her seizures began to drop. In early February 2014, she was transferred back to an ICU near her home in Wisconsin, where she later underwent rehabilitation therapy. She wrote in May 2014 to tell us that her last major seizure had occurred in April, and she has continued to be free of seizures since then. We remain in contact with her local neurology and rheumatology teams to assist in her follow-up care.

Discussion: Remain Open to All Possibilities

The tumor was found to be a ganglioneuroma, a rare tumor that contains neuronal tissue. In the course of attacking the tumor cells, the patient's immune system also attacked healthy brain cells and caused her epilepsy and ataxia, a process known as neurologic paraneoplastic syndrome. If the tumor had been a type that is typically linked to neurologic symptoms, such as an ovarian tumor, it would likely have been removed immediately. However, the adrenal location of a tumor in this age group is not commonly associated with these kinds of symptoms.

This case underscores the importance of keeping our minds open to all possibilities. Even when a patient has had symptoms for many years and has undergone extensive workup, we should persist in looking for the primary etiology. In this case, taking another close look at old tests solved the mystery.

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