P3.G141: Status Epilepticus Secondary to Intracranial Tuberculomas in a Child with Relapsed Familial HLH and Griscelli Syndrome

Introduction: Griscelli syndrome type 2 is a rare, autosomal recessive disorder characterized by hypopigmentation and immune dysregulation which can lead to the life-threatening development of familial hemophagocytic lymphohistiocytosis (HLH) and associated neurologic sequelae.

Case Description: A 5-year-old boy born into a second-degree consanguineous marriage in Karnataka, India with past medical history of familial HLH secondary to Griscelli syndrome (never having been transplanted) presented one year after treatment of relapsed HLH in status epilepticus.

The patient arrived to the hospital with altered sensorium and had two episodes of generalized tonic clonic seizures, with the first remitting spontaneously after 10 minutes and the second episode lasting 30 minutes. The seizure semiology consisted of unconsciousness, rhythmic limb movements, left gaze deviation and nystagmus, prominent oral automatisms, and urinary incontinence. The heart rate was 88 beats per minute, respiratory rate was 38 breaths per minute, blood pressure was 90/56 mmHg, and capillary oxygen saturation was 99% on ambient air. His seizure was successfully aborted with intravenous levetiracetam.

Prior to arrival, the patient was fully immunized per World Health Organization guidelines and adherent to chronic suppressive cyclosporine as well as prophylactic fluconazole and trimethoprim-sulfamethoxazole daily. No regression of developmental milestones was reported. He ate a strictly vegetarian diet and denied pork consumption. His chest x-ray was normal and PPD test was negative. MRI imaging of the brain revealed multiple ring-enhancing lesions with central diffusion restriction and a prominent lipid peak on MR spectroscopy, consistent with tuberculomas. CSF studies revealed elevated protein and ADA levels, though AFB stain and GeneXpert were negative. The patient improved and was discharged on antiepileptics and antitubercular therapy.

Discussion: Primary immunodeficiencies, also known as inborn errors of immunity, are associated with familial HLH. Whether or not allogenic stem cell transplant is possible based upon available resources, children in recovery from HLH require chronic immunosuppressive therapy which further heightens their risk of developing infections. In such cases, the diagnostic yield of certain infection screening tools may be low, as with tuberculin skin testing. The least invasive methods of testing are preferred to prevent complications. Extrapulmonary tuberculosis should be evaluated in endemic regions.

Conclusion: Infections of the central nervous system are the leading cause of acquired epilepsy in the developing world. Although relapsing HLH can cause neurologic manifestations, new or persistent seizures despite a positive response to immunochemotherapy warrant additional investigation.