Secondary Schizophrenia (109 page)

unequivocal disorder of the central nervous system

The main weakness of this study was an offshoot of
(CNS); the presence at some stage of shallow, incon-its greatest strength. The large sample size precluded
gruous affect, thought disorder, hallucinations, and
detailed psychiatric data being collected, so the ICD-9-delusions; and the absence, when psychotic, of fea-CM categories provide only bare bones phenomenol-

274

tures suggesting a delirium, dementia, dysmnesic syn-ogy. Nevertheless, under the very broad descriptive
Chapter 21 – Demyelinating disease and psychosis

rubric of psychosis, an unequivocal picture emerged
with a persecutory content, predominated. The find-of elevated rates of psychosis, in the order of 2% to 3%,
ings lend support to the ICD-10 notion of the psy-occurring in patients with MS. This study provides the
chosis being more akin to an “organic delusional disor-most compelling evidence to date that psychosis in MS

der,” with perceptual disturbances less noticeable and
occurs more frequently than chance dictates.

of secondary import.

Another frequently cited clinical observation in the
Distinguishing characteristics

literature of secondary psychosis, namely, the preservation of affective responses, also received empiri-

Temporal association

cal support
[6].
Thus, it would appear that when
Davison and Bagley’s MS review
[4]
revealed that in
patients with MS become psychotic, the predomi-36% of cases, the neurological and psychiatric symp-nant presentation is one of “positive” psychotic symptoms appeared at approximately the same time. Fur-toms (delusions, less often hallucinations) with rela-thermore, in 61.5% of cases, the psychosis appeared
tive preservation of affective responses. The “negative”

either 2 years before the onset of neurological symp-or “defect” state associated with schizophrenia, that
toms or after the onset. This temporal association in
is, apathy, impoverished speech and thought, together
approximately two-thirds of cases led the authors to
with blunted affect, is seldom seen. Notwithstanding
conclude that although psychosis secondary to MS was
this well-documented group profile that demarcates
rare, when it did occur, demyelination was most likely
the clinical picture of MS psychosis from schizophre-implicated in the pathogenesis. This result was not,
nia, it needs to be emphasized that on an individual
however, replicated by Feinstein and colleagues
[6]
in
level, it is frequently difficult to tell the conditions apart
a case control study of 10 psychotic MS patients. The
[8, 9].

mean duration of neurological symptoms before the
onset of psychosis was 8.5 years (range 0–19 years). In
Age of presentation

only one case was the diagnosis of MS made at the time
The mean age of first presentation of psychosis in
of psychosis onset.

schizophrenic patients is 23 years
[10],
which is considerably younger than that reported in two stud-

Clinical features

ies of MS patients with psychosis. Thus, Davison and
Feinstein and colleagues
[6]
examined the case notes
Bagley’s review
[4]
noted a mean age of onset of psy-of 10 psychotic MS patients treated at a tertiary referral
chosis a decade older and in Feinstein and colleagues’

center. Mental state was assessed retrospectively using
study
[6],
the average age was 36.6 years. A similar
the symptom checklist (SCL) derived from the Present
picture emerges from studies of other CNS disorders
State Examination (PSE)
[7].
From the SCL, half the
[11, 12, 13]
and the relatively later age of presentation
subjects were given a diagnosis of schizophrenia and
is therefore further evidence that sets psychosis sec-the other half an affective psychosis. Lack of insight
ondary to MS apart from schizophrenia.

characterized all the patients’ presentations. Persecu-The Alberta population-based study
[5]
does not
tory delusions occurred in more than two-thirds of
specifically address the age of onset of psychosis. But
cases and was the commonest psychotic feature. Non-the prevalence figures stratified by age are nevertheless
specific evidence of psychosis (which included height-informative. For example, the prevalence of “organic”

ened or changed perception, “minor” hallucinations,
psychosis was found to increase with age with peak
viz.
music, noises) was recorded in 60% of patients.

prevalence in the 65 years and over group. But the
Delusions of control (passivity) and delusions with
strongest relative effect (i.e., highest odds ratio) was
a sexual or fantastic content were present in a third
found in the 15-to 24-year age group. Although this
of patients, and delusions of reference noted in 1

observation can be explained by the fact that “organic”

in 5 patients. The symptom profile was notable for
psychosis is extremely rare in young patients without
the relative infrequency of well-formed hallucinations.

MS, it cannot obscure the fact that even young MS

Second-person auditory hallucinations were present in
patients still have a heightened risk of psychosis.

20% of patients as were visual hallucinations. Third-person auditory hallucinations (two or more voices
Gender ratio

commenting on the person) were found in only one
It is unclear whether the gender ratio noted in psy-

275

case. Thus, delusions in various forms, but particularly
chotic MS patients differs from that found in either MS

Organic Syndromes of Schizophrenia – Section 3

or late-onset schizophrenia. For example, Davison and
Subjects and controls underwent contiguous, mul-Bagley
[4]
reported 21 of 39 cases were male, which
tislice axial MRI of the brain. All scanning protocols
is at odds with the 1.5:1 female to male ratio in MS

included T2 weighted images that optimized lesion
and the equal gender ratio in schizophrenia (see Lewis,
detection.

1992
[14]
for a dissenting view). On the other hand,
Subjects were compared with controls with respect
the Alberta study did not find that gender modified the
to site and extent of lesions. MRI analysis was under-association between psychosis and MS
[5].

taken by a neuroradiologist blind to psychiatric diagnosis. The psychotic patients had a greater total
Etiology

lesion and periventricular lesion score, but these
were not statistically significant. Trends emerged for
Genetic links

a higher lesion score in the psychotic group for
If the psychosis associated with MS were simply
areas surrounding the temporal horns bilaterally. A
the chance co-occurrence of schizophrenia, then one
similar result was also obtained in the left trigone.

would expect to find increased evidence of schizophre-Combining the left temporal horn and adjacent left
nia in the relatives of the affected proband. Evidence is
trigone area scores produced a statistically signifi-scanty on this point, but does not support a familial
cant difference between the psychotic and control
link
[4].

groups.

A clearer picture of the difference in the distribu-

Viral hypothesis

tion of lesion scores between the psychotic and control MS patients was demonstrated by observing what
It has been postulated that similarities in disease
percentage of the total lesion score was present in
course, age of onset, geographical distribution, and
each particular area. In the controls, the total lesion
immunological response of patients with schizophre-score was distributed equally between periventricu-nia and MS imply some overlap with respect to patho-lar and other brain areas whereas in the psychotic
genesis
[15].
In particular, exposure to a virus at a cru-patients the periventricular lesion score contributed
cial developmental stage (in utero, childbirth, child-more than 60% of the total lesion score. This differ-hood) may be the common thread linking what are
ence was not, however, statistically significant. The
clinically two very different conditions. This viewpoint
most marked differences were present around the tem-fits well with theories of schizophrenia as a neurode-poral horns where the “percentage score” in the psy-velopmental disorder triggered by insult to the fetal
chotic patients was almost double that of the control
brain
[16]
. It has also been reported that infection
group. Thus, not only did the psychotic patients have a
during childhood with the herpes virus may leave
greater lesion score, but also lesions were differentially
some patients prone to develop MS in later life. Migra-distributed in periventricular areas and in particular
tion studies have shown that for those who emigrate
around the temporal horns of the lateral ventricles.

after adolescence, the risk of developing MS does not
A closer look at the individual patient data demon-change from that of their country of origin
[17].

strated that in all but one case control pair, the psy-Although theorizing offers intriguing possibili-chotic patient had a greater temporal horn lesion score
ties, the marked differences in clinical presentations
than the matched control.

between the two disorders outweigh any similarities,
Although the MRI data fit with findings from the
making a shared pathogen unlikely.

primary
[18, 19]
and secondary
[4, 11]
psychosis literature, it could not answer why only certain patients
MRI brain changes

with temporal lobe involvement became psychotic.

Compelling evidence linking brain changes in MS to
Whereas the study suggested a “threshold” lesion vol-psychosis comes from a case-control MRI study of 10

ume had to be exceeded before psychosis ensued, this
MS patients with psychosis and 10 without psychosis
did not invariably apply, as some patients with a large
[6],
who were matched for age, sex, duration of illness,
temporal lesion score did not become delusional. One
and physical disability. The following PSE
[7]
diag-can therefore posit that the presence of brain plaques in
noses were assigned: schizophrenia (2), schizoaffective
the temporal lobes is unlikely to fully explain the devel-psychosis (2), paranoid disorder (1), psychotic depres-opment of psychosis in all cases. Rather, brain lesions
276

sion (1), and mania with psychotic features (4).

superimposed on a premorbid vulnerability (genetic,
Chapter 21 – Demyelinating disease and psychosis

developmental, premorbid psychiatric history) seems
effects with both olanzapine and quetiapine have been
a more plausible explanation.

reported in one psychotic MS patient whereas ziprasi-done (a member of the benzothiazolylpiperazine class
Treatment

of antipsychotics) was well tolerated and effective
[21].

There are no empirically based treatment studies of
Should behavioral control still be required despite
psychosis associated with MS. Early reports found
adequate antipsychotic dosage, benzodiazepines may
electroconvulsive treatment
[8]
and insulin coma
[9]

be added. Lorazepam has the advantage of being given
to be ineffective in individual cases. The mainstay of
either via the oral or intramuscular route. Oral dosages
present treatment is antipsychotic medication
[6]
and,
rarely exceed 8 mg per day and the clinician should
given the often severe nature of the behavioral distur-bear in mind that the intramuscular dose is equivalent
bance, psychiatric hospitalization is often required in
to 2 to 21/

the acute stages.

2 times the oral dose, because it avoids the
first-pass metabolism.

In an analogous situation to that encountered with
the floridly manic patient, treatment can present a
considerable therapeutic challenge. Experience has
Outcome

taught that MS patients are frequently sensitive to
Earlier literature, much of it predating the appear-the side effects of antipsychotic medication. Thus,
ance of antipsychotic medication in the early 1950s,
high-potency drugs such as the butyrophenones (e.g.

reported that psychotic MS patients either recovered
haloperidol), which are associated with extrapyra-spontaneously, progressed from psychosis to demen-midal side effects (EPS), may further compromise
tia, or ran a relapsing-remitting course with respect to
patients’ mobility and balance, resulting in falls that
psychosis and MS that ultimately went on to demen-prove distressing to patients, family, and nursing staff.