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Psychotic Depression

An Atypical Initial Presentation of Multiple Sclerosis

Received January 22, 1996; revised June 21, 1996; accepted August 16, 1996. From the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. Address reprint requests to Dr. Clarke, Dalhousie University, Department of Psychiatry, QEII Health Sciences Centre, Victoria General Hospital, 8 South Mental Health Unit, 1278 Tower Road, Halifax, Nova Scotia, Canada B3H 2Y9.

Key Words: Psychosis • Depression • Multiple Sclerosis • Demyelinating Disease • Case Report

Multiple sclerosis (MS) is the most common of the demyelinating disorders. Mood symptoms in multiple sclerosis have been recorded in the literature for many years. Contradictory views on the relationship between these mood changes and the disease have been reported; it is likely that altered mood represents a complex interaction between personal vulnerability to mood disorder, lesions of cerebral demyelination, and disability.¹ Psychosis in MS is a far more rare occurrence.^2–4 It has been debated whether psychiatric abnormalities have ever truly been the first presentation of MS.⁵

We report a case of MS that was heralded by severe psychotic depression, in which initial physical evidence of neurological involvement was equivocal. The literature relevant to this phenomenon is reviewed.

Case Report

Mr. A., a 43-year-old manual worker, lived with his wife and teenage son. He was involuntarily hospitalized on a psychiatric unit after he stabbed himself in the epigastric area (abdomen). His problems had begun 3 weeks before the incident, when he woke up feeling "too depressed and tired to go to work." He had been "perfectly normal," according to his family, up until the day before. He had no history of psychiatric illness or any neurological complaints. His family history was also negative.

His mood rapidly deteriorated over the ensuing days. He fervently expressed the belief that he was a sexual deviant, a thief, and an alcoholic, and he insisted that he should be in jail. He believed that he was being monitored by the police and other unknown persons, and he disconnected his telephone lines. He claimed that he had spent all of his money on sex toys and pornographic materials and that he had performed sexual acts with a dead frog.

After 2 weeks of this morbid self-recrimination and persecutory delusions, he began to feel intensely suicidal. His suicide attempt brought him to psychiatric attention.

Mental status examination revealed a physically healthy-looking man who was overwrought and totally preoccupied with his alleged "sins." His thought form was well organized, but the content was replete with mood-congruent and mood-incongruent firmly held delusions. He was alert and oriented on admission, with a Folstein score of 28/30. Physical examination was normal, except for a right-positive Babinski reflex and slight nystagmus on left-lateral gaze.

Collateral history was that he was "sexually normal" and did not abuse alcohol or street drugs. He was described premorbidly as a responsible, cheerful, and outgoing man.

He was started on fluvoxamine maleate and perphenazine. He required constant 24-hour observation because of the intensity of his suicidal drive. He was referred for asssessment by the neurology service. Detailed examination by the neurologist revealed no further abnormality; notably, the cranial nerve, optic fundus, gait, and sensory examinations were normal. His Expanded Disability Status Scale was 2.0.⁶ Laboratory investigations, including computed tomography head scan, VDRL (syphilis test), electroencephalogram, and collagen vascular disease workup, were negative.

Mr. A.'s dose of fluvoxamine maleate was increased to 200 mg daily, and the perphenazine was upped to 16 mg daily. There was no improvement in his symptoms; lorazepam (4 mg/day) was added to the regimen to decrease agitation. He believed himself to be "a stalked and hunted man, who would never live to see the spring." Preparatory workup for a course of electroconvulsive therapy was initiated.

Cerebrospinal fluid from lumbar puncture revealed a high protein count and mild lymphocytosis; later analysis was positive for oligoclonal banding. Magnetic resonance imaging (MRI) of the brain demonstrated periventricular and deep white-matter changes consistent with demyelination. Mr. A. was booked for visual evoked-potential testing. This test revealed significant implicit time prolongation, with interocular differences consistent with demyelinating disease affecting the optic nerve. A working diagnosis of MS was made.

Mr. A. was started on a course of intravenous (iv) methylprednisolone (500 mg/day) for 5 days, followed by a tapering dosage of oral steroids. His psychiatric medication was continued. His delusions rapidly cleared over the 5 days of iv steroid use, and his mood state improved markedly. On Day 6, he was transferred to the psychiatry unit. Antidepresant therapy was continued, and he became euthymic by about Day 11. The antipsychotic medication was gradually tapered over a 2-week period. Follow-up over the subsequent 3 months revealed no new mood or neurologic symptoms.

Mr. A. acknowledged concealing recent alcohol use from his family. He had used alcohol at least once a week to the point of intoxication but had suffered no previous psychiatric or withdrawal phenomenon as a result. In addition, he had gained insight into the morbid nature of his previously held self-recriminatory sexual and persecutory delusions. He was also able to report an episode of transient paraesthesia in his hands, which had occurred several months before and had lasted for a few days.

Discussion

Since the days of Charcot, mood symptoms have been noted to occur in MS;⁷ the nature of the relationship is complex and incompletely understood.^8,9 Early reports of mood changes in MS stressed mood lability and euphoria as the more common symptoms.^10,11 Surridge stressed the importance of depressive symptoms, which he found in 27% of patients, and Surridge considered this to be "predominantly psychogenic and reactive in nature."¹²

This theory has not been supported by controlled studies. Dalos et al., in a sample of MS clinic patients, found that the prevalence of emotional distress was 39% in MS patients, compared with 12% of spinal-cord–injured patients, even though the control group had a significantly greater degree of functional impairment.¹³ In an outpatient sample of MS patients, Joffe et al. found the prevalence of major depression to be 14%, with a lifetime prevalence of 47%.¹⁴ The diagnosis of depression did not correlate with the degree of functional impairment. An epidemiological study of MS patients revealed that psychiatric contact for mood disturbance was significantly more common than in the control groups with temporal lobe epilepsy (TLE) and amyotrophic lateral sclerosis (ALS).¹⁵ These findings do not support the theory of depression occurring as a response to disability, uncertainty, or gravity of prognosis, given the vicissitudes of TLE and the ominous prognosis of ALS. Such theories do not explain the psychiatric morbidity in the case we presented.

It has been stated that MS presenting as psychiatric disturbance has received more attention than the empirical evidence supports.¹⁶ This contention is borne out by previously reported cases. These patient reports are noteworthy for clear clinical pictures of gross neurological deficit, acute confusional states, and/or long prior histories of unexplained neurological symptoms.^17,18 These cases are in sharp contrast to our patient, who never demonstrated any symptoms indicative of encephalopathy, although Mr. A. did not have formal neuropsychological testing. He was initially rejected by the neurology service because of the lack of clinical findings suggesting neurological disease. His transient prior history of paraesthesia was likely part of his MS process, but the condition preceded his florid psychiatric symptoms by only a few months.

Most previously reported cases and studies have found that neurological symptoms predate psychiatric ones by several months to years. There are very few reports ¹⁷, ^19–21 in which the psychiatric symptoms either are the presenting signs of MS or present simultaneously with the neurologic presentation. Nevertheless, the association of MS and major depression has been usually found to exist only after the diagnosis of MS has been made; the prevalence of depression is not different from the control subjects studied.²² Similarly, bipolar illness tends to occur, on average, 1 year after a definitive diagnosis of MS.²³ There are reports of depression (psychotic and nonpsychotic) in MS; unlike our patient, most of these cases had an established neurological diagnosis of MS for many years, as well as personal and family histories of mood disorder.¹, ²⁴ The association of MS with psychosis has appeared in the literature,²⁵, ²⁶ but this assertion has been rarely made.^2,3 In a series of 10 such psychotic MS patients at a major tertiary referral center, the phenomenology found was equally split between affective and schizophrenia-like presentations. The mean duration of psychosis was 5 weeks; diagnosed MS preceded the development of psychotic symptoms by an average of 8.5 years.⁴

Specific cerebral localization of lesions leading to neuropsychiatric presentations has been described for some diseases, for example, cerebrovascular accident and epilepsy. It is clear that cerebral MS cases are more likely to have psychiatric morbidity than noncerebral MS cases,¹², ¹⁴, ²⁷ although no consistent picture with MS plaque localization has been demonstrated. Laterality of lesions has not been found to be a significant factor, but there is some evidence that MS patients with psychiatric symptoms have a tendency to have a differential lesion distribution; the periventricular region is most often involved, at times in association with the temporal and frontal areas.⁴, ²⁸, ²⁹

Mr. A.'s history makes a compelling case for viewing certain psychiatric phenomena as arising directly from the demyelination process. The significance of this case is that it aptly demonstrates that neuropsychiatric presentations may be a more sensitive indicator of demyelination than physical symptoms³⁰ and may be the defining presentation of MS. This factor is an important clinical point for physicians working with these patients; psychiatric symptoms should not be assumed to be reactive in nature. It might be hypothesized that subcortical white-matter lesions lead to a depressive syndrome, as is commonly seen in subcortical dementia, and that lesions in limbic areas are more likely to lead to psychiatric rather than neurologic symptoms.

However, hypotheses about mechanisms of symptom production secondary to MS lesions are preliminary, as no direct relationship among lesion size, site, or number has been demonstrated for neurological or psychiatric features.³¹ The basis for these hypotheses may be related to the nature of demyelination itself or to the limitations of the tools used to localize the lesions. High-resolution MRI scans may address this need in part, but functional studies such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are usually more helpful. Such imaging may demonstrate areas of altered brain function—which may be remote from MS plaques—and could be the key to identifying disturbed functional networks and, therefore, the neuropathogenesis of symptoms. However, even PET and SPECT are still limited because of the heterogeneity of lesions in MS, and pathological changes may be still present in normal-appearing white matter.

Further study should also involve a more homogeneous group of subjects manifesting early onset of severe depression and/or psychosis, similar to our patient, because the etiology of symptoms is less likely to be significantly influenced by psychosocial factors. However, such a study would be difficult given that psychiatric symptoms as the first presenting signs of MS are not common. Investigation of these cases will be more likely to delineate the mechanisms by which the MS process leads to psychiatric symptoms.

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