Catatonic Disorder Due to a General Medical or Psychiatric Condition

With Mayo Clinic Institutional Review Board (IRB) approval, the Mayo Medical Index Registry was searched between the dates January 1, 1990 and December 31, 2010 for all patient charts linked to the search term “catatonia.” Our inclusion criteria were age ≥18 years at the time of diagnosis of catatonia, and fulfillment of DSM-IV-TR criteria for “catatonic disorder due to a general medical condition” (CD-GMC), “catatonic type, schizophrenia”, or “mood disorder with catatonic features.”⁷ Exclusion criteria included the presence of confounding diagnoses: Parkinson’s disease, neuroleptic malignant syndrome, serotonin syndrome, delirium, selective mutism, and akinetic mutism. Patients meeting the above inclusion and exclusion criteria were further divided into catatonic subtypes within the limits of the DSM-IV-TR criteria. The only modification to these criteria was for the allowance of patients meeting DSM-IV-TR criteria for schizoaffective disorder and catatonia to be included under the realm of the criteria outlined for “catatonic type, schizophrenia.” Neurologic causality was not assumed in the diagnosis of CD-GMC, and patients were classified within a psychiatric category if the catatonia was “better accounted for by another mental disorder,” and there was not evidence of a “direct physiological” relationship to the underlying secondary condition.⁷ Categorization required agreement of all the authors.

The historic medical records of all patients were exhaustively reviewed. Predetermined study variables (N=36) were recorded, including demographic, past medical, family, and social information. Treatment responses of catatonia to benzodiazepines and/or electroconvulsive therapy (ECT) were recorded in a binary fashion. Vital signs during the hospitalization were recorded as maximum values observed for heart rate, blood pressure, and core body temperature. Paraclinical variables that were recorded included the maximum creatine kinase (CK) value measured during a catatonic episode, in addition to routine indices taken from the complete blood count and basic metabolic profile at the time of presentation. Features of neurodiagnostic testing (electroencephalography [EEG]), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis) were also recorded.

EEG and MRI findings were analyzed in a dichotomous fashion, and classified as “abnormal” or “normal.” Only EEG abnormalities referable to cerebral dysfunction were classified as “abnormal” for the purpose of this study. Patients with benign EEG variants (i.e., wicket waves, small sharp spikes, and alpha variants), in addition to extracerebral artifacts (i.e., scalp muscle artifact) were considered to be “normal” for the purpose of our study. Radiographic abnormalities generally regarded as incidental were considered “normal,” including small-vessel ischemic white-matter changes, asymptomatic meningiomas, asymptomatic pituitary microadenomas, and asymptomatic chronic lacunar infarcts.

As part of a secondary analysis, patients were selected who had undergone both an ictal EEG, in addition to either a baseline pre-catatonic or a follow-up EEG after resolution of symptoms. Patients were excluded from this secondary observational analysis if they were treated with non-benzodiazepine antiepileptic medications or if there was not sufficient clinical documentation to determine that catatonia was absent during the pre- or post-EEG recording.

All analyses were carried out using the JMP Statistical Software Package (Version 8, SAS Institute Inc., Cary, NC). Descriptive statistics were used to describe the cohort and subgroups. Continuous variables were described as means with standard deviations (SD), or median and interquartile range (IQR) for non-normal variables. Nominal variables were described as counts and percentages. The primary objective of our study was to identify variables associated with an increased risk of an underlying diagnosis of CD-GMC relative to psychiatric catatonia. Univariate logistic-regression modeling was used to test for associations. Because of the low number of CD-GMC subjects, multivariate modeling was not performed.

A Bonferroni-adjusted alpha value was chosen in order to correct for multiple comparisons (N=36). Individual results were therefore considered to be statistically significant at p ≤0.001. For exploratory purposes, unadjusted p values are reported in the Results section.

A group of 236 unique patient charts were reviewed to accrue a final cohort with a total of 95 individuals, all meeting study inclusion and no exclusion criteria (Figure 1). DSM-IV-TR criteria were applied to these 95 patients, as described in the Methods section. The most common etiologic category was affective disorders (N=53; 55.8%), with psychotic disorders (N=22; 23.1%) and CD-GMC (N=20; 21%) representing comparable frequencies within the cohort. Major depressive disorder (MDD) was the single most frequently-occurring specific diagnosis (N=32; 33.7%).

The clinical and paraclinical features of our cohort are summarized in Table 1. The total cohort comprised 95 patients; 40% were male; with a mean age of 51.9 years (SD: 20.9) at the time of presentation. Among the patients presenting with CD-GMC, 9/20 (45%) had a history of psychiatric disease. Depression (N=7) was most commonly reported, with 4 patients having mild depressive symptoms, 2 having had a single major depressive episode, and 1 carrying a diagnosis of major depressive disorder (MDD). One additional patient was thought to have possible bipolar disorder, with insufficient chart documentation to confirm the diagnosis, and the final patient had a history of polysubstance abuse, but had been sober for at least 2 years. A history of a central neurologic problem was seen in 27/75 patients with psychiatric catatonia (36%). The most commonly reported neurologic problems were seizure (N=10), cognitive-domain difficulties (N=7), and traumatic brain injury (N=6). Patients with a history of cognitive problems could be classified as having mental retardation (N=3), probable Alzheimer’s disease (N=2), vascular dementia (N=1), and amnestic mild cognitive impairment (N=1). Less frequently reported neurologic histories included viral encephalitis (N=1), relapsing–remitting multiple sclerosis (N=1), normal-pressure hydrocephalus (N=1), bilateral, chronic subdural hematomas (N=1), and stroke (N=2).

In an attempt to protect against the identification of false-positive results, given multiple comparisons, a Bonferonni-adjusted significance level of p≤0.001 was utilized. A history of psychiatric disease (OR: 0.09; 95% CI: 0.02–0.31) was associated with a decreased odds ratio for a diagnosis of CD-GMC. A history of a clinical seizure (OR: 4.66; 95% CI: 1.46–14.39) was associated with an increased odds ratio for a diagnosis of CD-GMC, a result of only borderline statistical significance (p=0.008), given the conservative adjustment.

Additional clinical and paraclinical variables were assessed in the univariate logistic-regression model, which yielded a p value ≥0.5. Specifically, these included benzodiazepine use at presentation; histories of venous thrombosis, mental retardation, or head trauma; alcohol or tobacco use at presentation; and maximum heart rate, blood pressure, and temperature recorded during the episode. Additional paraclinical variables included laboratory indices at the time of presentation, and other descriptors of neurodiagnostic evaluation (e.g., “diffuse MRI abnormality,” “focal frontal EEG slowing”).

The etiologies underlying our 20 cases of CD-GMC (see Table 2) included encephalopathies (N=9), dementia (N=4), developmental (N=3), and other (N=4). The specific diagnoses were the following: acute encephalitis (N=4), paraneoplastic limbic encephalitis (N=1), chronic lymphocytic encephalomyelitis of unknown etiology (N=1), Hashimoto’s encephalopathy (N=1), corticosteroid-responsive autoimmune encephalopathy (N=1), relapsing encephalopathy of unknown etiology, suspect metabolic (N=1), probable behavioral-variant frontotemporal dementia (N=3), Lewy-body dementia (N=1), pervasive developmental disorder (N=1), Asperger’s syndrome (N=1), 22q13.3 microdeletion syndrome (periodic catatonia) (N=1), central nervous system lung cancer metastases (N=1), postictal psychosis with catatonia (N=2; one case, with simultaneous cannabinoid intoxication); and treatment-refractory epilepsy (N=1).

In all, 31 patients underwent MRI imaging of the head, which most commonly demonstrated diffuse findings (N=18) of mild-to-moderate generalized atrophy. More focal atrophy was seen in 4 patients, bifrontal in 2, and cerebellar in another 2. Focal encephalomalacia (N=7) was also seen, most frequently in patients with a history of head trauma or stroke. These latter changes were seen in the frontal (N=2), temporal (N=3), and parietal (N=2) cortical distributions. Finally, multifocal changes (N=3) were seen, in 1 patient with non-enhancing multiple sclerosis lesions, in typical periventricular and subcortical locations, without cortical atrophy; in another patient with CNS metastases involving the left parietal lobe and right cerebellum; and, finally, in an individual with chronic encephalomyelitis involving mainly the anterior left parietal lobe, brainstem, and right cerebellum.

Features of 70 independent EEG recordings from 53 patients during clinical catatonia are summarized in Table 3. The most common abnormality seen was generalized, symmetric slowing, most often in the theta frequency, but not uncommonly involving mixed theta/delta slowing. Superimposed focal slowing was not uncommon, and involved the temporal lobes more commonly than the frontal lobes. Generalized triphasic waves were more rarely seen. Asymmetry was seen in 9 recordings, most often involving left greater than right slowing. Finally, epileptiform abnormalities were seen in 6 patients, 2 of whom developed status epilepticus after ECT, and the remainder in patients with a history of a clinical seizure disorder.

Nine patients were identified who had undergone an ictal EEG recording, in addition to having had either a baseline or follow-up EEG study. Baseline EEGs had been documented in only 3 patients at a mean time lapse of 3.3 years preceding the catatonia (range: 1 month to 82 months). At baseline, 1 patient had diffuse mixed theta/delta slowing; 1 had focal bi-temporal slowing; and 1 had a normal EEG. Follow-up EEGs were obtained in 6 patients at a mean time of 5.2 months after the ictal catatonic EEG recording (range: 5 days to 16 months). Overall, with the clinical development of catatonia, either worsening (N=2), or persistent (N=1) changes were seen. An improved EEG pattern was not seen in any of the 3 patients. With the clinical resolution of catatonia, all 6 patients showed improvement in at least 1 EEG abnormality, most commonly generalized slowing, but also resolution of frontal intermittent rhythmic delta activity (FIRDA) in 1 patient. However, complete improvement was not the rule, and persistent bi-temporal slowing was seen in 1 patient, and generalized slowing was seen in another.