A 28-year-old man with a history of common variable immunodeficiency (CVID) and panhypogammaglobulinemia was found to have liver lesions and adenopathy near the aortic arch. A liver biopsy revealed T-cell lymphoma, and he was subsequently treated with four cycles of CHOP chemotherapy (cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisone) and two cycles of DHAP chemotherapy (dexamethasone, high dose cytarabine and cisplatin). Chemotherapy had no significant effect on T-cell lymphoma (Non-Hodgkin's lymphoma, NHL) progression, and therefore, the patient underwent bone marrow transplant.
The patient began an immunosuppressive conditioning regimen of cyclophosphamide and total body irradiation (TBI) prior to an allogenic HLA-matched related bone marrow transplant from his sister and engrafted by day 20. Post-transplant, he received monthly intravenous immunoglobulin (IVIG) infusions and 550 mg of cyclosporine daily. The patient developed graft-versus-host disease (GvHD) of the liver, and the patient was started on prednisone and continued cyclosporine. While tapering prednisone, the patient was hospitalized for herpes simplex I of the mouth and nose and bacterial sinusitis, treated successfully with acyclovir and cefepime, respectively : both suspected to have occurred due to a weakened immune system from prednisone and cyclosporine.
Days after his hospitalization for herpes simplex and sinusitis, at 7.5 months' post-transplant, the patient was readmitted due to cyclosporine toxicity with a blood level of 1467 ng/ml (therapeutic range: 100-200 ng/ml). He experienced cortical blindness and a single focal impaired awareness seizure and MRI showed increased occipital/parietal signal intensity consistent with posterior reversible encephalopathy syndrome (PRES). There was no evidence of any pre-existing epileptogenic lesions on MRI. Symptoms improved upon immediate replacement of cyclosporine with tacrolimus and administration of phenytoin. Besides cyclosporine neurotoxicity, he did not have any preexisting risk factors for epilepsy development such as febrile seizures, family history of seizures/epilepsy or childhood seizures/epilepsy.
The next two years following cyclosporine toxicity, the patient was seizure-free although this was complicated with acute GvHD of the liver and chronic GvHD of the skin. At 33 months' post-transplant, he experienced a generalized tonic-clonic (GTC) seizure and remained in non-convulsive status epilepticus until treated with phenytoin. MRI at the time of seizure recurrence (Fig. 1) showed a subtle signal intensity increase in the right insular cortex and hippocampus and atrophy in the right parietal lobe. An EEG was abnormal with frequent spike-wave discharges with occasional delta slow waves in the right temporal region. His medical history, EEG and neuroimaging were consistent of a focal seizure tendency. Lumbar puncture was clear and negative for adenovirus, herpes and varicella making an encephalitis etiology unlikely. PCR confirmed the negative herpes culture.
The patient continued to have drug-resistant seizures. His seizures were mostly focal with impaired awareness and progressively increased in frequency to 4-5 times per week. Antiseizure drug trials of lamotrigine, levetiracetam, phenytoin and oxcarbazepine were largely unsuccessful in controlling his seizures. No autoantibody titers were tested to rule in an autoimmune etiology. MRI (Fig. 1) and PET imaging at 2 years' post-seizure recurrence revealed right mesial temporal sclerosis (MTS) and right temporal hypometabolism, respectively. Seizure semiology consisted of focal aware seizures of odd smell and taste, most consistent with medial temporal localization. Ictal EEG localized to the right anterior temporal lobe and interictal EEG showed right temporal slowing with occasional right anterior temporal sharp waves. Wada testing of visual and verbal memory and language all lateralized to the left hemisphere. A neuropsychological cognitive assessment revealed bilateral mesial temporal dysfunction and moderate anterograde memory deficits. Presurgical workup (Table 1) and discussion at our multidisciplinary epilepsy conference indicated the patient for a right anterior temporal lobectomy and amygdalohippocampectomy without intracranial electrode monitoring at eight years' post-transplant. Pathology showed subpial gliosis in the right anterior temporal lobe with dentate cell dispersion and right hippocampal sclerosis. The surgery was uncomplicated, and the patient developed no cognitive deficits. A 3-month postoperative neuropsychological cognitive assessment indicated stable or improved functioning in most cognitive domains with a less severe anterograde memory deficit compared to the preoperative assessment. At the eight-year follow-up, with the exception of two episodes concerning for focal aware seizures at the two-year follow-up, the patient was seizure free since surgery (Engel Score Class Ib) and remains in NHL remission 16 years' post-transplant.