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Understanding Psychosis in a Veteran with a History of Combat and Multiple Sclerosis Angela Lee, AB; and Kalpana I

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Understanding Psychosis in a Veteran with a History of Combat and Multiple Sclerosis Angela Lee, AB; and Kalpana I CASE IN POINT Understanding Psychosis in a Veteran With a History of Combat and Multiple Sclerosis Angela Lee, AB; and Kalpana I. Nathan, MD A patient with significant combat history and previous diagnoses of multiple sclerosis and unspecified schizophrenia spectrum and other psychotic disorder was admitted with acute psychosis inconsistent with expected clinical presentations. Angela Lee is a Medical ultiple sclerosis (MS) is an immune- present with distinct magnetic resonance imag- Student, and Kalpana mediated neurodegenerative disease ing (MRI) findings, such as diffuse periventric- Nathan is a Clinical 8 Associate Professor Mthat affects > 700,000 people in the ular lesions. Still, no conclusive criteria have (Affiliated) in the US.1 The hallmarks of MS pathology are axonal been developed to distinguish MS presenting Department of Psychiatry or neuronal loss, demyelination, and astrocytic as psychosis from a primary psychiatric illness, and Behavioral Sciences, both at Stanford gliosis. Of these, axonal or neuronal loss is the such as schizophrenia. University School of main underlying mechanism of permanent clini- In patients with combat history, it is possi- Medicine in California. cal disability. ble that both neurodegenerative and psychotic Kalpana Nathan also is MS also has been associated with an in- symptoms can be explained by autoantibody an Attending Psychiatrist in the Veterans Affairs creased prevalence of psychiatric illnesses, formation in response to toxin exposure. When Palo Alto Health Care with mood disorders affecting up to 40% to soldiers were deployed to Iraq and Afghanistan, System in California. 60% of the population, and psychosis being they may have been exposed to multiple tox- Correspondence: 2 The link Angela Lee reported in 2% to 4% of patients. icities, including depleted uranium, dust and 9 ([email protected]) between MS and mood disorders, including fumes, and numerous infectious diseases. Gulf bipolar disorder and depression, was docu- War illness (GWI) or chronic multisymptom illness mented as early as 1926, with mood disorders (CMI) encompass a cluster of symptoms, such hypothesized to be manifestations of central as chronic pain, chronic fatigue, irritable bowel nervous system (CNS) inflammation.3 More re- syndrome, dermatitis, and seizures, as well as cently, inflammation-driven microglia have been mental health issues such as depression and hypothesized to impair hippocampal connec- anxiety experienced following exposure to these tivity and activate glucocorticoid-insensitive in- combat environments.10,11 flammatory cells that then overstimulate the In light of this diagnostic uncertainty, the au- hypothalamic-pituitary-adrenal axis.4,5 thors detail a case of a patient with significant Although the prevalence of psychosis in combat history previously diagnosed with MS patients with MS is significantly rarer, averag- and unspecified schizophrenia spectrum and ing between 2% and 4%.6 A Canadian study other psychotic disorder (USS & OPD) presenting by Patten and colleagues reviewed data from with acute psychosis. 2.45 million residents of Alberta and found that those who identified as having MS had a 2% CASE PRESENTATION to 3% prevalence of psychosis compared with A 35-year-old male veteran, with a history of 0.5% to 1% in the general population.7 The MS, USS & OPD, posttraumatic stress disor- connection between psychosis and MS, sim- der, and traumatic brain injuries (TBIs) was ad- ilar to that between mood disorders and MS, mitted to the psychiatric unit after being found has been described as a common regional by the police lying in the middle of a busy inter- demyelination process. Supporting this, MS section, internally preoccupied. On admission, manifesting as psychosis has been found to he reported a week of auditory hallucinations S32 • FEDERAL PRACTITIONER SPECIAL ISSUE • JUNE 2019 from birds with whom he had been communi- at age 18 years to serve in the Marine Corps cating telepathically, and a recurrent visual hallu- (2001-2006). His service included deployment cination of a tall man in white and purple robes. to Afghanistan, where he received a purple He had discontinued his antipsychotic medica- heart. Upon his return, he received BA and MS tion, aripiprazole 10 mg, a few weeks prior for degrees. He married and had 2 daughters but unknown reasons. He was brought to the hos- became estranged from his wife. By his most pital by ambulance, where he presented with recent admission, he was unemployed and living disorganized thinking, tangential thought pro- with his half-sister. cess, and active auditory and visual hallucina- On the first day of this most recent psychi- tions. The differential diagnoses included USS & atric hospitalization, he was restarted on aripip- OPD, schizophrenia, schizoaffective disorder and razole 10 mg daily, and a medicine consult was ruled out substance-induced psychotic disorder, sought to evaluate the progression of his MS. No and psychosis as a manifestation of MS. new onset neurologic symptoms were noted, but The patient had 2 psychotic episodes prior he had possible residual lower extremity hyper- to this presentation. He was hospitalized for his reflexia and tandem gait incoordination. The ep- first psychotic break in 2015 at age 32, when he isodes of psychotic and neurologic symptoms had tailed another car “to come back to reality” appeared independent, given that his psychiatric and ended up in a motor vehicle accident. Dur- history preceded the onset of his MS. ing that admission, he reported weeks of thought The patient reported no visual hallucinations broadcasting, conspiratorial delusions, and rac- starting day 2, and he no longer endorsed audi- ing thoughts. Two years later, he was admitted tory hallucinations by day 3. However, he con- to a psychiatric intensive care unit for his second tinued to appear internally preoccupied and was episode of severe psychosis. After several trials noticed to be pacing around the unit. On day 4 of different antipsychotic medications, his most he presented with newly pressured speech and recent pharmacologic regimen was aripiprazole flights of ideas, while his affect remained euthy- 10 mg once daily. mic and his sleep stayed consistent. In combi- His medical history was complicated by nation with his ongoing pacing, his newfound 2 TBIs, in November 2014 and January 2015, symptoms were hypothesized to be possibly with normal computed tomography (CT) scans. akathisia, an adverse effect (AE) of aripiprazole. He was diagnosed with MS in December 2017, As such, on day 5 his dose was lowered to 5 mg when he presented with intractable emesis, left daily. He continued to report no hallucinations facial numbness, right upper extremity ataxia, and demonstrated progressively increased emo- nystagmus, and imbalance. An MRI scan re- tional range. A MRI scan was done on day 6 in vealed multifocal bilateral hypodensities in his case a new lesion could be identified, suggesting periventricular, subcortical, and brain stem a primary MS flare-up; however, the scan identi- white matter. Multiple areas of hyperintensity fied no enhancing lesions, indicating no ongoing were visualized, including in the right periatrial demyelination. After a neurology consult corrob- region and left brachium pontis. More than orated this conclusion, he was discharged in sta- 5 oligoclonal bands on lumbar puncture con- ble condition on day 7. firmed the diagnosis. As is the case with the majority of patients He was treated with IV methylprednisolone with MS-induced psychosis, he continued to followed by a 2-week prednisone taper. Within have relapsing psychiatric disease even after MS 1 week, he returned to the psychiatric unit with treatment had been started. Unfortunately, be- worsening symptoms and received a second cause this patient had stopped taking his atypi- dose of IV steroids and plasma exchange treat- cal antipsychotic medication several weeks prior ment. In the following months, he completed a to his hospitalization, we cannot clarify whether course of rituximab infusions and physical ther- his psychosis stems from a primary psychiatric apy for his dysarthria, gait abnormality, and vi- vs MS process. sion impairment. His social history was notable for multi- DISCUSSION ple first-degree relatives with schizophrenia. He Presently, treatment preferences for MS- reported a history of sexual and verbal abuse related psychosis are divided between atypi- and attempted suicide once at age 13 years by cal antipsychotics and glucocorticoids. Some hanging himself with a bathrobe. He left home suggest that the treatment remains similar JUNE 2019 • FEDERAL PRACTITIONER SPECIAL ISSUE • S33 Psychosis in Patient with MS between MS-related psychosis and primary of MRI imaging done at his initial psychotic epi- psychotic disorders in that atypical antipsy- sodes cannot exclude a primary MS diagnosis. chotics are the standard of care.12 A variety of Still, his lack of MRI findings at his most recent atypical antipsychotics have been used suc- hospitalization, negative symptomatology, and cessfully in case reports, including zipradisone, strong history of schizophrenia make a primary risperidone, olanzapine, quetiapine, and ar- psychotic disorder likely. ipiprazole.13,14 First-generation antipsychotics Following his future clinical course will be and other psychotropic drugs that can pre- necessary to determine the etiology of his psy- cipitate extra-pyramidal AEs are not recom- chotic episodes. Future episodes of psycho- mended given
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