Partially empty sella with generalized epileptiform discharges presented as manic episode in an elderly female

Sir, Epidemiological studies have shown that the first episode of mania is rare among the elderly.[12] There is no consensus guideline for older age bipolar disorder (OABD), but organic causes should be ruled out in all OABDs.[3] Pituitary lesions and seizure disorders have been reported to be associated with OABD. However, empty sella without endocrine abnormality or generalized epileptiform discharge without any seizure episode has never been reported to be associated with OABD. Hereby, we present a case of elderly onset mania with electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities. CASE DESCRIPTION A 63-year-old female presented with a history of sudden-onset behavioral changes after a febrile episode. The patient had symptoms of irritability, decreased need for sleep, increased activity, and authoritativeness. She would claim to be goddess “Manasa Mata” and would threaten to curse her family members if questioned her power. On many occasions, the patient would be partially dressed while meeting male family members and relatives. There were several incidents when the patient would fight with family members, alleging them poisoning her food. The patient had a history of fever (up to 100°F) a couple of weeks before the onset of psychiatric symptoms. There was no history of seizure, head trauma, substance use, prior forgetfulness, or repeated mistakes in daily routine activities. There was no past or family history of any psychiatric illness. On mental state examination, the patient was oriented to time, place, and person with increased speech and psychomotor activity. Her affect was exalted with prolixity in the tempo of thought and grandiose and secondary persecutory delusions in thought content. General physical examination was normal with body mass index of 20 kg/m2and blood pressure of 122/78 mmHg. Detailed neurological examination and lobar function test did not reveal any abnormality. The Young Mania Rating Scale (YMRS)[4] score at the time of hospitalization was 28 and the Montreal Cognitive Assessment[5] score was 27. All routine blood investigations were normal [Table 1]. Non-contrast computed tomography head revealed age-related cortical atrophy, whereas MRI brain revealed partially empty sella [Figure 1]. Her EEG revealed generalized epileptiform discharges [Figure 2]. She was already on tablet olanzapine 5 mg daily which was subsequently increased to 10 mg daily. Within the next 7 days, her symptoms improved markedly, and her YMRS score became 6. She was discharged on the same treatment as family members were not willing to stay beyond 10 days. After 3 months, in her routine hospital visits, she was continued to be euthymic on the same treatment.Table 1: Blood investigationsFigure 1: T2-weighted magnetic resonance imaging brain (sagittal section) revealing cerebrospinal fluid-filled sella (orange arrow) with compressed pituitary at the bottom (white arrowhead) suggestive of partially empty sellaFigure 2: Electroencephalography with 10–20 international electrode placement system with monopolar/bipolar referential-generalized epileptiform discharge with a frequency of 8–10 Hz and 40–50 V (similar finding was obtained on repeat electroencephalography)DISCUSSION Primary empty sella syndrome (ESS) happens when defect above the pituitary gland results in an increase in pressure, causing the gland to flatten out. It is commonly associated with obesity and high blood pressure in women.[67] Secondary ESS is due to injury, surgery, or radiation therapy of the pituitary gland. ESS can present with various neuropsychiatric symptoms, secondary to endocrine abnormalities or electrolyte imbalance.[78] Yang et al. reported a case of late-onset mania in a 69-year-old female with ESS, where they found syndrome of inappropriate antidiuretic hormone (SIADH) and symptoms resolved after correction of plasma sodium level.[8] In this case, however, there was no evidence of obesity, hypertension, or overt brain pathology. All efforts were made to search for any possible pituitary dysfunction. All hormone assays were normal except for marginally raised prolactin (can be explained by antipsychotic treatment). A possibility of SIADH was also ruled out given normal serum osmolality [Table 1]. Generalized periodic epileptiform discharges (GPEDs) are rare EEG patterns. Common etiologies include metabolic disorders and infectious disease.[9] In this case, despite a recent history of fever, all biochemical parameters came normal including blood culture, C-reactive protein, and erythrocyte sedimentation rate. However, GPEDs can cause kindling of neuronal pathways, leading to psychiatric manifestations such as mania. Lateral hypothalamic kindling has shown to induce manic-like behavior in a rat model.[10] Current literature is also not clear if GPED with or without psychiatric symptoms (such as late-onset mania) to be treated with antiepileptics or not.[9] Another sizable factor was Vitamin B12 deficiency in this patient, which has been reported to be associated with a manic episode.[11] This patient also received parenteral B12 during ward stay, but the clinical response was apparent even before B12 supplementation was started. A general rule of thumb in medicine is if a patient has multiple symptoms and signs, clinicians should try to explain them by one illness rather than different diagnoses for each one. The current case hinted at the possibility of an organic cause of manic episode (late age of onset, preceding febrile episode, vitamin deficiency, EEG and MRI abnormalities, and rapid response to treatment), but we failed to establish the plausible mechanism for the same. This left us in the dilemma if these associations were merely coincidental or had any causal link! Further studies are needed to explore late-onset mania and its neurobiology, to give us a better insight about the illness and its management. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgments We are grateful to Dr. Divyani Garg, MD, DM (Neurology) – Assistant professor of Neurology, LHMC and SSKH, for her expert inputs. Dr. Siddharth Sarkar, Associate professor, National drug dependence treatment centre, AIIMS, New Delhi for his inputs to improve the manuscript.

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