Clinical Neuroimaging Findings in Catatonia: Neuroradiological Reports of MRI Scans of Psychiatric Inpatients With and Without Catatonia

This study was a case-control study comparing neuroradiological abnormalities in clinical reports of MRI brain scans of patients with catatonia with those of psychiatric patients without catatonia. Anonymized electronic health care records from patients seen in the South London and Maudsley National Health Service Foundation Trust (SLaM), London, were accessed through the Clinical Records Interactive Search (CRIS). The CRIS system has previously been described (16) and is approved by the Oxfordshire C Research Ethics Committee (ref. 18/SC/0372). This specific study was approved by the CRIS Oversight Committee (ref. 17–102).

Data are owned by a third party, Maudsley Biomedical Research Centre Clinical Records Interactive Search (CRIS) tool, which provides access to anonymized data derived from SLaM electronic medical records. These data can be accessed only by permitted individuals from within a secure firewall (i.e., the data cannot be sent elsewhere). (For more information, contact [email protected].)

Cases of catatonia were defined as having a clinician diagnosis of catatonia and at least two features on the Bush-Francis Catatonia Screening Instrument, a reliable and validated instrument for the detection of catatonia (7, 17, 18), as described in previous work by this group (19). Because this was a heterogeneous population with a range of diagnoses, the comparison group comprised all patients admitted to psychiatric wards in the Trust who had never had a catatonia diagnosis. All patients with catatonia had also been psychiatric inpatients.

The exposure was an abnormal MRI scan, as judged by the reporting neuroradiologist. The clinical scanner was a 1.5 Tesla GE HDx, with scans collected for clinical reporting, including high-resolution T1-weighted, T2-weighted, and FLAIR sequences without contrast. The electronic health care records and MRI clinical radiological reports were extracted, where available, from the electronic records for all patients admitted to a hospital ward who met the selection criteria described above. The following data were extracted from structured fields in the records: age at index date, sex, race-ethnicity, involuntary detention within 2 weeks following the index date, and primary ICD-10 diagnosis. The index date for patients with catatonia was the date of the first identified catatonic episode; for the comparison group, the date of hospital admission was used as the index date. When a diagnosis had been made prior to the index date, the most recent diagnosis prior to the index date was used; when this was not available, the earliest diagnosis up to 6 months after the index date was used. MRI scans were reported by consultant neuroradiologists, of whom there are currently eight. Scans that occurred at any time before the index date or within 90 days after the index date were included. Scans obtained more than 90 days after the index date were excluded on pragmatic grounds, because there was a higher risk that they included abnormalities that had developed after the index illness. Where there were multiple scans available for one patient, the scan that was nearest to the index date was used. The procedure is illustrated in Figure 1.

All available MRI reports from 2008 to 2018 were compiled in a spreadsheet. The reports were categorized and numerically coded for the presence of abnormalities by their anatomical location, pathological description, and lateralization. In scans with multiple abnormalities, each abnormality was coded separately by these criteria to minimize loss of data. Extracranial abnormalities were excluded. All reports were evaluated independently by two investigators (R.J. and R.T.), who were blinded to the diagnostic groups and each other’s assessments. Where there was disagreement, a third investigator (J.P.R.) arbitrated. The study size was determined pragmatically based on the number of available cases.

Following data collection, small cell sizes were merged based on a priori relationships between categories blind to group membership. The anatomical areas were merged based on embryological brain structure, and the pathologies were merged according to the main underlying mechanism.

The potential confounders considered were age on date of scan, sex (male or female), Black race-ethnicity, and diagnostic group. We chose to adjust for these potential confounders because they have previously been associated with differences in brain MRI findings (20–24) and have been associated with risk of catatonia in prior studies (25–28). Ethnicity categories were grouped according to the preferred categories of the United Kingdom Office for National Statistics (29). Mixed or multiple ethnic groups were combined with “other” ethnic group to avoid small cell sizes. Primary diagnoses were grouped as organic and neurodevelopmental disorders (ICD-10 codes F00–F09, F70–89, F90, F95, and non-F codes), schizophrenia and related disorders (F20–F29), mood disorders (F30–F39), neurotic disorders (F40–F59), personality and behavioral disorders (F50–F69, F91–F94, and F98), and substance use disorders (F10–F19).

We investigated whether having an abnormal MRI scan was associated with greater odds of reporting catatonia; we used univariable and multivariable logistic regression models adjusted for age, sex, and race-ethnicity.

Given the differing proportions of organic or neurodevelopmental diagnoses across the groups, we conducted a sensitivity analysis in which we excluded these diagnoses. As a secondary analysis, among the abnormal scans, we conducted a logistic regression for catatonia based on the number of abnormalities per scan, adjusted for age, sex, Black race-ethnicity, and diagnostic group.

We analyzed lateralization, anatomical location, and pathology by the number of scans that had at least one abnormality in the specified category. This was done to avoid scans with many abnormalities excessively weighting the analyses. To calculate the differences between proportions having different categories of abnormalities, we used Fisher’s exact test, because there were numerous small cell sizes.

Missing data were assumed to be missing at random. Therefore, to explore the impact of missing data on our estimates, as a sensitivity analysis, we imputed missing exposure data for participants with complete outcome data by using multiple imputation by chained equations. We imputed 20 data sets using all variables included in the models, as well as a number of auxiliary variables that were associated either with one of the variables of interest or with missingness of one of the variables of interest. The variables included in the final imputation model were abnormal scan, catatonia, age at scan, sex, Black race-ethnicity, diagnostic group, electroconvulsive therapy use within 2 weeks after index, age at index (either onset of catatonia or hospital admission), date of birth, date of scan, diastolic blood pressure, systolic blood pressure, date of death, time from referral to index date, time from index date to documentation, end date of catatonic episode, Health of the Nation Outcome Scale (HoNOS) score, HoNOS date, index date, duration of admission, Mini-Mental State Exam score, episode order, death within follow-up, involuntary detention, and validity of MRI report. (The observed and imputed data are compared in Table S1 in the online supplement to this article.) The analysis used Stata MP, version 15.1.

This article was written according to the STROBE guidelines (30). (The STROBE checklist is available in Table S2 in the online supplement.)

Of 1,456 patients with catatonia and 24,956 patients in the comparison group, complete MRI scan reports were extracted for 790 subjects, who had a total of 816 scans. After extraction of one scan per patient, there were 79 scans in the catatonia group (5.4% of all patients with catatonia) and 711 scans in the comparison group (2.8% of all patients in the comparison group), as illustrated in Figure 1. A total of 188 included scans were conducted prior to the index date, and 602 were conducted on or after the index date. The median time from index date to scan was 27 days (interquartile range [IQR]=5 to 48), and the range was –2,679 to 90 days. Sixty-nine scans were conducted within 2 weeks of the index date.

A scan result was missing for 25,622 (97.0%) participants, age at index for 1,904 (7.2%), sex for four (0.0%), and race-ethnicity for 393 (1.5%). Patients of Black race-ethnicity appeared more likely to have an MRI scan, but the groups were similar in terms of age and sex (see Table S3 in online supplement).

Table 1 summarizes the demographic and disease-related data of the participants in this study. Mean age at the time of the scan was 36.4 years (SD=17.3; range, 10–78) for the catatonia group and 44.5 years (SD=19.9; range, 7–93) for the comparison group. Handedness of subjects is not available in this data set.

In total, 365 of 790 scans (46.2%) were reported as abnormal. As shown in Table 2, 34.2% of the catatonia group had an abnormal scan, compared with 47.5% of the comparison group. In the unadjusted complete-case analysis, having an abnormal MRI scan was associated with lower odds of a diagnosis of catatonia (odds ratio [OR]=0.57, 95% confidence interval [CI]=0.35, 0.93, p=0.03). After adjustment for confounders (age, sex, Black race-ethnicity, and diagnostic group), there was no longer evidence of an association (OR=1.11. 95% CI=0.58, 2.14, p=0.75). In sensitivity analyses run on imputed data sets, the results were consistent with those of complete case analyses (OR=0.92, 95% CI=0.48, 1.74; adjusted OR=1.30, 95% CI=0.53, 3.20). (Abnormalities by diagnostic group are reported in Table S4 in the online supplement.)

Among the scans reported as abnormal, there were between one and 10 abnormalities. In the patients with catatonia, the median number of abnormalities was two (IQR=1–3). In the comparison group, the median number of abnormalities was two (IQR=1–4). The unadjusted OR for catatonia diagnosis as predicted by the number of abnormalities was 0.84 (95% CI=0.65, 1.08, p=0.17). After adjustment for age, sex, Black race-ethnicity, and diagnostic group, the OR was 0.96 (95% CI=0.75, 1.23, p=0.74).

Table 3 shows that most abnormal scans had at least one bilateral abnormality in both the catatonia and the comparison groups. We found no evidence of difference in lateralization of abnormalities between the groups (p=0.98).

Abnormalities were reported across various brain regions, as shown in Table 3. Most abnormalities were in the forebrain in both groups. We found no evidence of differences in anatomical location of abnormalities between the groups (p=0.73). In the catatonia group, among 25 scans with forebrain abnormalities, the specific location of the abnormalities was diffuse cerebral (N=18), frontal (N=7), parietal (N=4), temporal (N=3), occipital (N=1), basal ganglia (N=1), thalamus (N=1), pituitary gland (N=1), and optic nerve (N=1). (Some scans had more than one abnormality.) In terms of the nine scans with hindbrain abnormalities in the catatonia group, the specific locations were the cerebellum (N=6) and pons (N=3).

The numbers of scans reporting different categories of pathology are reported in Table 3. The most common pathologies in both groups were brain atrophy and small vessel disease. Additionally, the scans of the catatonia group showed similar frequencies of white matter lesions and small vessel disease. There was no evidence of a difference in pathology of abnormalities between the groups (p=0.75).