Psychosis: Is it a medical problem?
Ms. B hears voices and is paranoid but has no other symptoms of a psychotic disorder. The challenge: narrow the differential diagnosis and determine what’s causing her hallucinations.
Within 4 days of starting risperidone, Ms. B’s auditory hallucinations and paranoia have lessened and her insight is improved. We recommend increasing the dosage to 2 mg/d because we feel that 1 mg/d will not sufficiently control her symptoms. She remains paranoid but is reluctant to increase the dosage for fear of adverse effects, though she has reported none so far.
Brain MRI taken the night Ms. B was admitted shows:
- multiple focal, well-defined hyperintense periventricular lesions on fluid-attenuated inversion recovery (FLAIR)- and T2-weighted images (Figure 2). Some lesions are flame-shaped.
- a 1.5-cm lesion adjacent to the right frontal horn showing a hyperintense signal on T2-weighted images and a hypointense signal on T1-weighted images without contrast enhancement. White-matter edema surrounds this lesion.
- no gadolinium-enhancing lesions.
Two radiologists confirm possible demyelination, suggesting multiple sclerosis (MS). Final report of initial brain CT shows lowdensity, periventricular white matter changes consistent with the MRI findings.
Results of subsequent laboratory tests are normal. Erythrocyte sedimentation rate is slightly elevated at 35 mm/hr, suggesting a possible autoimmune disorder. ECG shows sinus bradycardia, and chest x-ray and MR angiogram are unremarkable, as are EEG and visual evoked potential results.
Lumbar puncture and CSF studies show increased immunoglobulin G to albumin ratio. CSF fluid is clear, blood counts and protein are normal, Gram’s stain and culture are negative, and cytologic findings show a marked increase in mature lymphocytes. These results suggest inflammation, but follow-up neurologic exam is unremarkable.
Figure 2 FLAIR-weighted image after Ms. B’s brain MRI
Right 1.5-cm lesion adjacent to right frontal horn and multiple left hyperintense lesions on fluid-attenuated inversion recovery (FLAIR)-weighted image.
The authors’ observations
Determining disease dissemination in time and space is key to diagnosing MS. Clinical presentation or MRI can determine both criteria (Table 1). Ms. B’s lesions and CSF results suggest that MS has disseminated throughout her body, but neurologic examination shows no objective clinical evidence of lesions.
Neuropsychological testing might help evaluate Ms. B’s cognition and executive functioning, but these deficits do not specifically suggest MS. The cortex, particularly the prefrontal cortex, is believed to coordinate organization, planning, and socially appropriate behavior. MS typically involves white matter rather than the cortex, but researchers have suggested that MS-related demyelination might disrupt the axonal circuits that connect the cortex to other brain areas.18
Increased lesion load has been correlated with decreased cognitive function. Neuropsychological testing could indirectly point to a lesion load increase by recording decreased cognitive function, but this decline cannot be attributed to MS without an MRI.
Ms. B’s psychotic symptoms could be clinical evidence of MS, but we cannot solidify the diagnosis until we establish dissemination in time. To do that, we need a second MRI 3 months after the first one. Concurrent late-onset paraphrenia and MS is possible but rare.
Table 1
Findings needed to determine MS diagnosis based on clinical presentation
| Clinical presentation | Findings needed for MS diagnosis |
|---|---|
| >2 clinical attacks* Objective clinical evidence of >2 lesions | None |
| >2 clinical attacks Objective clinical evidence of 1 lesion | Dissemination in space by MRI |
| or | |
| >2 MRI-detected lesions consistent with MS plus positive CSF | |
| or | |
| Await further attack implicating a different site | |
| 1 clinical attack >2 objective clinical lesions | Dissemination in time by MRI |
| or | |
| Second clinical attack | |
| 1 clinical attack 1 objective clinical lesion | Dissemination in space by MRI |
| or | |
| >2 MRI-detected lesions consistent with MS plus positive CSF | |
| and | |
| Dissemination in time by MRI | |
| or | |
| Second clinical attack | |
| * Clinical attack: neurologic disturbance defined by subjective report or objective observation lasting at least 24 hours. | |
| Source: Reference 5 | |
Follow-up: where is she?
Ms. B is discharged after 10 days. She denies hallucinations, and staff notices decreased paranoia, brighter affect, and improved insight. We tell her to continue taking risperidone, 1 mg/d.
Three weeks later, Ms. B sees an outpatient psychiatrist. She is paranoid, guarded, and has not been taking risperidone.
Because Ms. B’s previous MRI results are suspect, we ask the hospital’s neurology service to examine her. Findings are unremarkable, but the neurologist recommends a followup brain MRI in 3 months or sooner if symptoms emerge. More than 2 years later, she has not completed a second MRI or contacted her psychiatrist or neurologist.
The authors’ observations
Ms. B’s case highlights the importance of:
- recognizing an atypical presentation of a primary psychotic disorder
- checking for a medical cause of psychosis (Table 2)
- knowing which psychiatric symptoms are common in MS.
Despite absence of neurologic symptoms, Ms. B’s psychosis could have been the initial presentation of MS, which is more prevalent among psychiatric inpatients than in the general population.6,7 In a prospective study,8 95% of patients with MS had neuropsychiatric symptoms, and 79% had depressive symptoms. Hallucinations and delusions were reported in 10% and 7% of MS patients, respectively. These findings suggest that mood disturbances are considerably more common than psychosis among patients with MS.
