British Journal of Psychiatry (1992), 161, 680—685
Psychotic Illness in Multiple Sclerosis A Clinical and Magnetic ResonanceImaging Study ANTHONY FEINSTEIN, GEORGE du BOULAY and MARIA A. RON
Ten patientswith multiplesclerosis(MS) andpsychosiswere assessedusingthe PresentState Examination,andmatchedretrospectivelywith respectto age,disability,durationof symptoms, and diseasetype wIth 10 MS patientswithoutpsychosis.BothgroupsunderwentMRI of the brain. Therewas a trendfor the psychoticgroupto havea highertotal lesionscore,particularlyaround the periventricularareas.Thisreachedstatisticalsignificanceinthe areasaroundthe temporal horn.In allcases,neurologicalsymptomsprecededthe onsetof psychosis.The psychoticgroup alsohada laterageof onsetof psychosisthan psychoticpatientswithout braindisease.These resultspointtoanaetiologicalassociationbetweenthepathologicalprocessof MS andpsychosis.
The presence of psychiatric symptoms as part of the
that
clinical picture of multiple sclerosis (MS) has long
1986; Joffe
been recognised. The commonest symptoms reported
often psychotic symptoms are an integral part of
are those of depressive mood states with psychotic disorders featuring far less frequently. However, the possibility that psychoses occurring in the presence
this picture.
of demonstrable brain disease may throw light on the causation of schizophrenia and manic-depressive
logical illness. The aim of the report is firstly, to analyse the presentation, course and symptoms of these patients and secondly, to attempt a clinico pathological correlation by studying the size and
in the general
population
et al, 1987). However,
(Schiffer it is unclear
et al, how
We report here a group of MS patients who experienced psychotic symptoms during their neuro
disease makes this association particularly interesting (Feinstein & Ron, 1990).
location of brain lesionsdetected by magnetic resonance
Syndromes resembling schizophrenia in association appear to be rare (Davison & Bagley, 1969; Mathews,
imaging (MRI)incomparison with amatched group of non-psychotic MS patients. it is thereby hoped to darify
1979;
the association between MS and psychotic disorders.
with MS have been reported Awad,
1983).
in the literature,
A similar
conclusion
but
can be
drawn from Johnstone et al's (1987) study of 268 consecutive,
first-admission
schizophrenic
patients
Method
investigated for physical disease, none of whom had MS. However,
similarities
between
the course of the
A total of 10patients with definite MS who had experienced
two conditions and certain common epidemiological
psychotic symptoms and had MRI scans had been referred
features such as age of onset, unimodal age distri bution and geographical clustering led Stevens (1988) to postulate that the two may share an infectious or immunological cause. In a series of 39 published cases collected by Davison & Bagley (1969) both conditions had started simultaneously in a third of cases, while
to the psychiatricdepartmentof the National Hospital for Neurologyand Neurosurgeryoverthe past sixyears; these constituted the study group. The criteria of Poser et a!
in a further
25°lothe psychosis
began within two
years either side of the onset of the neurological
that psychotic symptoms may have been associated lobe pathology.
Major depression is, by contrast, common in MS, being reported
in a quarter
to a half of patients
(Minden & Schiffer, 1990), and the frequency of bipolar affective disorder appears to be greater than
psychosis
implied
the presence
of delusions
and/or
hallucinations in the absence of dementia or delirium. This allowed the inclusion of patients with both schizophrenia and affective psychosis. Levels of physical disability were rated from case notes using the Expanded
symptoms and this temporal link was interpreted as signalling an aetiological connection. More recent studies of psychiatric morbidity in MS (Ron & Logsdail, 1989), while reporting that onset of neuro logical symptoms came first in most cases, suggested with the presence of temporal
(1983) were used to defme clinically definite MS, while the term
Disability Status
Scale (EDSS; Kurtzke, 1983). Nine of these patients had
beenencounteredin the courseof two other studieslooking at psychiatricmorbidityin MS(Ron &Logsdail,1989)and psychosis in patients with demonstrable brain disease (Feinstein & Ron, 1990),and a further patient not previously reported has also been included. A control group of MS patients who had not experienced a psychotic illness was used for comparison. Attempts were
made to match each subject individually with a control in terms of age (±5 years), sex, EDSS (±1.0)and duration of MS (±3years). In one case the age matching was seven years apart and in another the difference in duration of
680
PSYCHOSISAND MS illness was six years. Controls were drawn from a large group
of patients taking part in a study of MRI abnormalities in
681
Data were analysed using the Statistical Package for the Social Sciences (SPSS;
Norusis,
1989). Non-parametric
MS at the same hospital. Although cognitiveassessment statistics were used because of the ordinal system of rating was not part of this study, no gross cognitive impairment the MR images.Comparisonsbetweenpatient and control had been clinicallyobservedin any ofthe psychoticgroup, groups with respect to total lesion score were undertaken and it had been noted in only one of the control subjects. using f-tests. In the psychotic group, mental state was assessed retrospectivelyusing a symptom check-list(SCL)derived Results
from the Present State Examination (Wing et a!, 1974).
From the SCL computerisedCATEGO, subclasses,classes, Despite the demographic differences between two of the and diagnoses were generated. Of these, the subclasses patients and their controls, the overall group matching was were preferred as they give the most information con veryclose(Table1).Thepsychoticgroupwasequallydivided cerning the phenomenology of the disorder, e.g. ‘¿nuclear schizophrenia' implying the presence ofSchneiderian first rank symptoms. Subjects and controls underwent contiguous, multislice axial MRI of the brain (Picker superconducting
system)
usinga groupstandardtransverseimagingplane(MacManus et a!, 1989). All scanning protocols included T2 weighted
images that optimised lesion detection. Thus a spin echo (SE)@,@
was used with a field of view of 30 cm. The
number of excitations was 2, the matrix 128x 256 pixels and the phase-encoding gradient horizontal. Patients and controls had been scanned over a period of six years, during which time changes to the MRI scanner and software upgrades ensured that better images were obtained. Thus, soon after installation the strength of the magnet was increased from 0.25 to 0.5 tesla, and slice thickness reduced
into either relapsing-remitting (RR) or chronic-progressive (CP) MS while the control groups had 6 CP and 4 RR
patients. Eight patients from each group had been treated with steroids since the onset of MS. but in only a single subject had steroids been given before the onset of psychosis. Table 1 Demographic characteristics of MS patients with and
without psychosis (mean (s.d.) where applicable) Psychotic group
Control group
(n=10)
(n=10)
Age: (8.9)Sex5M:5F5M:5FDuration: years39.6
(10.8)37.9 (7.1)10.6 (2.3)4.6(2.1)
(4.2)EDSS4.9 years10.0
from 10mm to 5 mm. Despitethese changes,the imaging protocols and slicethickness were the same in all patient and control groups. It was not, however, possiblein one case to match the images for strength of magnetic field.
The EDSSand MRIwereperformedwhenthe patientswere psychoticin eight cases. In the remainingtwo cases, MRI was undertaken one and three years after the psychotic episode
with a normal
mental state at the time.
Subjects were compared with controls with respect to site
Psychiatric features
The mean age of onset of psychosiswas 36.6years (range 26-52). Using the SCL four subjects obtained a CATEGO subclass of mania, two of nuclear schizophrenia, two of
schizoaffective psychoses and one each ofparanoid disorder
and psychotic depression. The schizoaffective and paranoid and extentof lesions. MRI analysis was undertakenby a neuroradiologist (0 du B) blindto psychiatric diagnosis. patients were incorporated into the schizophrenic rubric
In assessingthe MRI, a systemused in previousstudiesat
which assumes primacy in a hierarchical classification
the National Hospital (Ormerod eta!, 1987)was followed.
system. Thus two broad categories
The size and presence of lesions were recorded in the
affective psychosis each with five subjects were obtained.
following
There were no differences between the schizophrenic and affective subgroups with respect to any demographic variables, duration of MS symptoms or age of onset of the
periventricular
areas:
body of the ventricles;
frontal, temporal and occipital horns; trigone; and third and fourth
ventricle.
Tbese seven areas provided
a penventricular
of schizophrenia
and
score. A further eight areas of brain parenchyma were also examined, namely internal capsule; basal ganglia; frontal, parietal, temporal and occipital lobes; brain stem; and
psychosis. They did however differ in physical disability —¿
cerebellum. The lobes of the cerebrum were defined as including not only cortex, but also underlying white matter. Planes separating lobes are projected from their cortical
The meanduration of neurologicalsymptomsbeforethe
boundaries to the foramen of Munro or the lateral ventricular trigone, as appropriate. The largest lesion in each particular area was scored using a four-point scale (0-3)
according to the greatest diameter measured (0=1 mm, 1=2-5mm, 2=6—10mm, 3=>l0mm). A total lesion
the affective subgroup had a significantlyhigher EDSS (means 6.4 v. 3.5, Z=2.l,
P