Andrew Francis

Catatonia. I. Rating scale and standardized examination

To facilitate the systematic description of catatonic signs, we developed a catatonia rating examination, rating scale and screening instrument. We constructed a 23‐item rating scale and a truncated 14‐item screening instrument using operationalized definitions of signs ascribed to catatonia in published sources. Inter‐rater reliability was tested in 44 simultaneous ratings of 28 cases defined by the presence of ≥2 signs on the 14‐item screen. Inter‐rater reliability for total score on the rating scale was 0.93, and mean agreement of items was 88.2% (SD 9.9). Inter‐rater reliability for total score on the screening instrument was 0.95, and mean agreement of items was 92.7% (SD 4.9). Diagnostic agreement was high based on criteria for catatonia put forth by other authors. Seven per cent (15/215) of consecutively admitted patients to an academic psychiatric in‐patient facility met criteria for catatonia. It is concluded that catatonia is a distinct, moderately prevalent neuropsychiatric syndrome. The rating scale and screening instrument are reliable and valid. Their use facilitates diagnosis, treatment protocols, and cross‐study comparisons.

Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.

Case material and retrospective studies support the use of both lorazepam and ECT in treating catatonia, but few prospective investigations exist and none employ quantitative monitoring of response. In this study we test their efficacy in an open, prospective protocol, and define a‘lorazepam test’ with predictive value for treatment. Twenty‐eight patients with catatonia were treated systematically with parenteral and/or oral lorazepam for up to 5 days, and with ECT if lorazepam failed. Outcome was monitored quantitatively during the treatment phase with the Bush‐Francis Catatonia Rating Scale (BFCRS). In 16 of 21 patients (76%) who received a complete trial of lorazepam (11 with initial intravenous challenge), catatonic signs resolved. A positive response to an initial parenteral challenge predicted final lorazepam response, as did length of catatonic symptoms prior to treatment. Neither demographic variables nor severity of catatonia predicted response to lorazepam. Four patients failing lorazepam responded promptly to ECT. It is concluded that lorazepam and ECT are effective treatments for catatonia. The rating scale has predictive value and displays sensitivity to change in clinical status.

An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method.

OBJECTIVE The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications. The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel. PARTICIPANTS Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure. EVIDENCE A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process. CONSENSUS PROCESS After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009. RESULTS Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4°F or > 38.0°C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, ≥ 25% above baseline; blood pressure fluctuation, ≥ 20 mm Hg (diastolic) or ≥ 25 mm Hg (systolic) change within 24 hours; tachycardia, ≥ 25% above baseline; and tachypnea, ≥ 50% above baseline. CONCLUSIONS These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings.

Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia

Electroconvulsive therapy (ECT) and lorazepam are effective treatments for catatonia. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency and therefore is not recommended in the routine practice of ECT. We report 5 prospectively identified cases of catatonia treated either sequentially or concurrently with lorazepam and ECT. In each case, the combination of lorazepam with ECT was superior to monotherapy. This apparent synergism, its possible mechanisms, and its implications for treating catatonia are discussed.

Catatonia: Diagnosis, Classification, and Treatment

Catatonia is a distinct neuropsychiatric syndrome that is becoming more recognized clinically and in ongoing research. It occurs with psychiatric, metabolic, or neurologic conditions. It may occur in many forms, including neuroleptic malignant syndrome. Treatment with benzodiazepines or electroconvulsive therapy leads to a dramatic and rapid response, although systematic, randomized trials are lacking. An important unresolved question is the role of antipsychotic agents in treatment and their potential adverse effects.

Residual catatonic state following neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is usually a self-limited disorder, with most cases resolving within 2 weeks after antipsychotic drug discontinuation. However, the course of NMS may not always be short-lived. In this report, the authors describe five patients who developed a residual catatonic state that persisted after acute hyperthermic symptoms of NMS had subsided and compare them with 27 similar cases in the literature. Two of our patients recovered gradually with supportive treatment. Three patients were treated with electroconvulsive therapy (ECT). Of these, two showed a positive response, although one died later of intercurrent pneumonia. A third patient did not respond to ECT, but recovered gradually thereafter. Although dopamine agonists or benzodiazepines have been advocated for the treatment of residual symptoms in previous case reports, ECT was the treatment most often associated with a rapid response and no mortality, even in patients refractory to pharmacotherapy. In conclusion, catatonic and parkinsonian symptoms of NMS may persist as a residual state lasting for weeks to months after more fulminant acute symptoms abate. These residual symptoms may be more likely to develop in patients with pre-existing structural brain disorders. Although patients may improve gradually with supportive care or pharmacotherapy, ECT can often be highly effective in treating the residual catatonic state that follows NMS.

Recovery of tectal nicotinic-cholinergic receptor sites during optic nerve regeneration in goldfish

The concentration of cholinergic nicotinic-like sites as measured by alphabungarotoxin (alphaBuTX) binding, decreased in the goldfish (Carassius auratus) optic tectum after optic nerve disconnection. Initially, the rate of loss of sites is greater than the rate of tissue or protein degradation in experiments where disconnection was achieved either by unilateral optic nerve crush or by enucleation of one eye. When the crushed optic nerve is allowed to regenerate and form behaviorally potent connections, the number and concentration of these sites appears restored. Pharmacological studies indicate that the alphaButTX binding site in the goldfish optic tectum has a drug binding profile similar to that seen at central or peripheral alphaBuTX sites in other species.

Catatonic signs in neuroleptic malignant syndrome

The study assessed catatonic signs in neuroleptic malignant syndrome (NMS). Records of inpatients meeting both stringent research criteria and DSM-IV criteria (n = 11) or only DSM-IV criteria (n = 5) for NMS were identified. The records were systematically rated on a 23-item rating scale for the presence of catatonic signs. Scores for NMS severity were related to the number of catatonic signs. Fifteen patients met both research criteria for catatonia and DSM-IV motor criteria for organic catatonia. The severity scores of NMS correlated with the number of catatonic signs (Spearman rho = +.71, P < .005). We conclude that multiple catatonic signs are present in NMS and the severity of NMS predicts the number of catatonic signs.

ECT for prolonged catatonia.

Objective and Background Electroconvulsive therapy (ECT) is highly effective for acute catatonia but its use in prolonged catatonia is not well established. We report three cases of prolonged catatonia with medical complications or comorbidities treated by ECT. Method Case reports. Results A 24 year-old woman developed fever and autonomic instability after parenteral neuroleptics. Catatonia and autonomic signs persisted for 14 weeks. After minimal improvement from lorazepam, 15 bilateral ECTs led to resolution. A 26-year-old woman with a history of lupus erythematosus, complicated by lupus cerebritis with lesions in the cortex and basal ganglia and a communicating hydrocephalus, was catatonic for 9 weeks. Lorazepam produced marginal improvement. A series of 14 bilateral ECTs led to improved mobility, speech, and interaction, but the response was less robust than Case 1. A 40-year-old man with mental retardation and intermittent psychosis developed severe neuroleptic malignant syndrome and remained catatonic for 4 months. After lorazepam produced minimal improvement, his catatonia resolved with 20 bilateral ECTs. Conclusions ECT may improve prolonged catatonia with complex medical comorbidities, but may require many treatment sessions. Gross cerebral pathology may predict a less robust response. As for acute catatonia, ECT may resolve prolonged catatonia after benzodiazepines have failed.

Recognition and Treatment of the Catatonic Syndrome

We define the catatonic syndrome and review the history of the concept of catatonia, including its recent acceptance as a syndrome. Diagnosis of the catatonic syndrome, with its associated extensive differential diagnoses related to systemic and mental disorders, is addressed. Catatonia is related to variants of the syndrome, such as lethal (malignant) catatonia and the neuroleptic malignant syndrome (NMS). Medical sequelae of these conditions are outlined. The literature on the treatment of the catatonic syndrome is reviewed, and a suggested approach to treatment and management of catatonic patients in the intensive care unit is provided. An hypothesis regarding the neuropathophysiological basis for the syndrome is also offered.