UNASSIGNED: Catatonia is a complex psychomotor syndrome commonly associated with psychiatric disorders. However, hospitalists encounter this condition on medical floors, where it is typically due to an underlying medical, especially neurological, etiology. Delays in the diagnosis of catatonia are common and lead to worsened outcomes for patients, including a multitude of medical complications, such as venous thromboembolism and stasis ulcers. Catatonia due to a medical condition is less likely to respond to benzodiazepine therapy; identification and treatment of the underlying cause is crucial.
UNASSIGNED: This article provides a practical review of the catatonia literature, with a focus on diagnosis, workup, and management of catatonia for patients admitted to medical hospitals.
UNASSIGNED: With greater knowledge about catatonia, internists are uniquely positioned to recognize and initiate treatment.

OBJECTIVE: Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links.
METHODS: We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including \"catatonia\", \"neuroleptic malignant syndrome\" and \"antipsychotic agents\" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients\' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes.
RESULTS: We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %).
CONCLUSIONS: Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS.

Patients with cerebral palsy, a group of movement disorders with motor, and possibly communication and behavioral features that mimic catatonic signs, may benefit from efforts to improve the detection and treatment of comorbid catatonia. Given that cerebral palsy frequently co-occurs with conditions associated with catatonia, such as autism spectrum disorder, epilepsy, intellectual disability, and mood and psychotic disorders, lifetime prevalence of catatonia in this population may be high.
This study aimed to systematically review the literature on catatonia and the related condition of neuroleptic malignant syndrome (NMS) in patients with cerebral palsy while presenting 2 additional cases of catatonia.
We used the terms \"cerebral palsy\" in combination with \"catatoni∗,\" related terms for catatonia, and \"neuroleptic malignant syndrome\" to query Ovid MEDLINE (1948 to November 28, 2022), PsycINFO, Cumulative Index to Nursing, and Allied Health Literature, and Embase for applicable case reports. The Neuroleptic Malignant Syndrome Information Service database was also manually searched.
In addition to our 2 catatonia reports, we identified 10 reports of catatonia in patients with cerebral palsy, as well as 8 reports of NMS. Patients with both conditions responded well, and sometimes rapidly, to treatment. Notably, of the 5 patients with catatonia and cerebral palsy who received electroconvulsive therapy, 2 developed recurrent self-limited hyperthermia posttreatment. We also identified several cases of baclofen withdrawal, which can be life threatening because of seizure risk, presenting with NMS-like features in patients with cerebral palsy who had malfunctioning intrathecal baclofen pumps for spasticity management.
Given frequent comorbidity of conditions associated with catatonia in patients with cerebral palsy, as well as routine treatment with medications that can induce NMS, such as metoclopramide and anticholinergics, catatonia and NMS may be underreported in the cerebral palsy patient population, despite being highly treatable. Possible underdiagnosis of catatonia in patients with cerebral palsy may be because of misattribution of overlapping features between the 2 conditions to cerebral palsy. Clinicians should be aware of possible recurrent self-limited fever when using electroconvulsive therapy to treat patients with catatonia and cerebral palsy while also being vigilant for intrathecal baclofen withdrawal when encountering NMS-like features in patients with cerebral palsy.

Catatonia is a neuropsychiatric syndrome consisting of psychomotor abnormalities caused by a broad range of disorders affecting brain function. While the nosological status of catatonia is no longer restricted to a subtype of schizophrenia in standardized diagnostic systems, the character, course, and clinical significance of catatonia in people with schizophrenia remain unclear. Evidence suggests that catatonia could be a nonspecific state-related phenomenon, a fundamental core symptom dimension of schizophrenia, or a subcortical variant of schizophrenia. Either way, the validity of catatonia in schizophrenia is clinically significant only insofar as it predicts prognosis and response to treatment. Most contemporary clinical trials of antipsychotics have targeted schizophrenia as an overly broad unitary psychosis neglecting any differential response defined by phenomenology or course. However, early naturalistic studies showed that catatonia predicted poor response to first-generation antipsychotics in chronic schizophrenia and case reports cautioned against the risk of triggering neuroleptic malignant syndrome. More recent studies suggest that second-generation antipsychotics, particularly clozapine, may be effective in schizophrenia with catatonic symptoms, while small randomized controlled trials have found that the short-term response to ECT may be faster and more significant. Based on available data, conclusions are limited as to whether antipsychotics are as effective and safe in acute and chronic schizophrenia with catatonic symptoms compared to other treatments and compared to schizophrenia without catatonia. Further studies of the pathophysiology, phenomenology, course and predictive value of catatonia in schizophrenia are worthwhile.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare, potentially fatal neurological emergency, that is seen in Parkinson\'s Disease (PD) patients and mimics neuroleptic malignant syndrome. The most common trigger for PHS is sudden withdrawal of anti-parkinsonian medications, specifically levodopa. However, it can also be due to Deep Brain Stimulation (DBS) device malfunction. In this work, we describe three cases of PHS; the first of which is related to DBS battery depletion, and the remaining two to dopaminergic withdrawal. Additionally, we will include the results of a literature review on PHS, its etiologies, presentation, and management.

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia. Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series. 182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality. Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis presents commonly with psychiatric symptoms. One cohort of these patients reported that antipsychotic administration led to neuroleptic intolerance (NI) in 19% of them, which was preventable by a prompt encephalitis diagnosis. To date, there is no clear description of the \"neuroleptic intolerance\" spectrum in general or during anti-NMDAR encephalitis. We aimed to synthesize epidemiological and clinical characteristics of patients with NI and confirmed anti-NMDAR encephalitis, the time to the encephalitis diagnosis, the disease course, outcomes at discharge, and associated factors. We systematically searched three databases, to include clinical cases, case series, and observational studies. Additionally, we reported one clinical case. Results were summarized using narrative synthesis and the quality of the included studies was assessed. We included 22 records representing 40 patients (28 females; mean age, 24.6). Overall, the evidence quality was low. Initially, most cases were admitted in psychiatric wards (70%) with purely psychiatric symptoms (37.5%). However, most of them developed subtle concomitant neurological symptoms. The mean time to anti-NMDAR encephalitis diagnosis was 26.7 days, which was triggered by the NI in six patients. We found no association between clinical variables as delayed diagnosis, admission to psychiatric wards or the presence of malignancy with outcome variables as unfavorable outcomes at discharge, ICU, or mechanical ventilation requirement. A thorough neurological examination in young patients with new-onset psychiatric symptoms could help emergency physicians, neurologists, and psychiatrists suspect anti-NMDAR encephalitis earlier. Awareness of NI as a potential side effect during suspected or confirmed anti-NMDAR encephalitis is encouraged.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable disease that presents with symptoms similar to neuroleptic malignant syndrome (NMS).
METHODS: We describe a 28-year old female who initially presented with headaches, behavioral changes, anxiety, lip tremors, and rigidity of extremities. She was prescribed with olanzapine and later manifested with neuroleptic malignant syndrome symptoms such as decrease in sensorium, muscle rigidity, hyperthermia and tachycardia. Further investigation showed presence of bilateral ovarian teratoma and anti-NMDAR antibodies in her serum and cerebrospinal fluid. Symptoms resolved after intravenous high-dose methylprednisolone, bilateral oophoro-cystectomy, and intravenous immunoglobulin administration. Overlapping pathological mechanisms of anti- NMDAR encephalitis and NMS were discussed. Ten patients with anti- NMDAR encephalitis and NMS were noted in a review of literature. Prognosis was favorable and intervention ranged from supportive to methylprednisolone and intravenous immunoglobulin administration, plasma exchange and teratoma resection.
CONCLUSIONS: Anti- NMDAR encephalitis patients are at risk for NMS due to antipsychotic intolerance and other interrelated pathophysiological mechanisms. The overlap between the signs and symptoms of anti-NMDAR encephalitis and NMS poses a diagnostic dilemma and warrants a careful investigation and management.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal drug adverse reaction. There are still few studies of this entity in the child-adolescent population.
OBJECTIVE: Describe the clinical, laboratory and therapeutic characteristics of children and adolescent patients with NMS. Analyse the grouping of symptoms present in NMS in the same population.
METHODS: A MEDLINE/PubMed search of all reported cases of NMS from January 2000 to November 2018 was performed and demographic, clinical, laboratory and therapeutic variables were identified. A factorial analysis of the symptoms was performed.
RESULTS: 57 patients (42 males and 15 females) were included, (mean age 13.65 ± 3.89 years). The onset of NMS occurred at 11.25 ± 20.27 days with typical antipsychotics and at 13.69 ± 22.43 days with atypical antipsychotics. The most common symptoms were muscle stiffness (84.2%), autonomic instability (84.2%) and fever (78.9). The most common laboratory findings were CPK elevation and leucocytosis (42.1%). The most used treatment was benzodiazepines (28.1%). In the exploratory factorial analysis of the symptoms we found 3 factors: 1) \"Catatonic\" with mutism (0.912), negativism (0.825) and waxy flexibility (0.522); 2) \"Extrapyramidal\" with altered gait (0.860), involuntary abnormal movements (0.605), muscle stiffness (0.534) and sialorrhoea (0.430); and 3) \"Autonomic instability\" with fever (0.798), impaired consciousness (0.795) and autonomic instability (0.387).
CONCLUSIONS: NMS in children and adolescents could be of 3 types: catatonic, extrapyramidal and autonomic unstable.

Neuroleptic malignant syndrome (NMS) is a potentially fatal, idiosyncratic reaction to antipsychotics. Due to low incidence of NMS, research on risk factors of mortality associated with NMS is limited.
Two authors independently searched Medline/Embase/Cochrane/CINAHL/PsychINFO databases for case reports with author-defined NMS published in English until 05/30/2020. Demographic, clinical, treatment, and outcome data were independently extracted following PRISMA guidelines. NMS severity was rated using the Francis-Yacoub scale. Mortality risk factors were identified using a multivariable regression analysis including all characteristics that were significantly different between NMS cases resulting vs. not resulting in death.
683 cases with NMS were analyzed (median age = 36 years, males = 62.1%). In a multivariable model, independent predictors of NMS mortality were lack of antipsychotic discontinuation (odds ratio (OR) = 4.39 95% confidence interval (CI) = 2.14-8.99; p < 0.0001), respiratory problems (OR = 3.54 95%CI = 1.71-7.32; p = 0.0004), severity of hyperthermia (Unit-OR = 1.30, 95%CI = 1.16-1.46; p < 0.0001), and older age (Unit-OR = 1.05, 95%CI = 1.02-1.07; p = 0.0014). Even in univariate, patient-level analyses, antipsychotic formulation was not related to death (oral antipsychotic (OAP): n = 39/554 (7.0%) vs. long-acting injectable (LAI): n = 13/129 (10.1%); p = 0.2413). Similarly, death with NMS was not related to antipsychotic class (first-generation antipsychotic: n = 38/433 (8.8%) vs. second-generation antipsychotic: n = 8/180 (4.4%); p = 0.0638). Non-antipsychotic co-treatments were not associated with NMS mortality.
Despite reliance on case reports, these findings indicate that presence of respiratory alterations, severity of hyperthermia, and older age should alert clinicians to a higher NMS mortality risk, and that antipsychotics should be stopped to reduce mortality, yet when NMS arises on LAIs, mortality is not increased vs. OAPs.