Intrinsic neural network dynamics in catatonia.

Catatonia is a transnosologic psychomotor syndrome with high prevalence in schizophrenia spectrum disorders (SSD). There is mounting neuroimaging evidence that catatonia is associated with aberrant frontoparietal, thalamic and cerebellar regions. Large-scale brain network dynamics in catatonia have not been investigated so far. In this study, resting-state fMRI data from 58 right-handed SSD patients were considered. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate and test the underlying intrinsic components (ICs) in SSD patients with (NCRS total score ≥ 3; n = 30) and without (NCRS total score = 0; n = 28) catatonia. Functional network connectivity (FNC) during rest was calculated between pairs of ICs and transient changes in connectivity were estimated using sliding windowing and clustering (to capture both static and dynamic FNC). Catatonic patients showed increased static FNC in cerebellar networks along with decreased low frequency oscillations in basal ganglia (BG) networks. Catatonic patients had reduced state changes and dwelled more in a state characterized by high within-network correlation of the sensorimotor, visual, and default-mode network with respect to noncatatonic patients. Finally, in catatonic patients according to DSM-IV-TR (n = 44), there was a significant correlation between increased within FNC in cortico-striatal state and NCRS motor scores. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states.

Should Catatonia Be Conceptualized as a Pathological Response to Trauma?

ABSTRACT: Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

The Development of Kraepelin's Concept of Dementia Praecox: A Close Reading of Relevant Texts.

In 1893 and 1896, in his fourth and fifth textbook editions, Emil Kraepelin brought together 3 syndromes to form the first and second of his 2 prequels to dementia praecox (DP), a definitive version of which he would propose in his 1899 sixth textbook edition. These syndromes, which would become hebephrenic DP, catatonic DP, and paranoid DP, each had distinct histories. Hebephrenic DP was derived from syndromes first proposed by Hecker, and catatonic DP was derived from syndromes first proposed by Kahlbaum, and then both were substantially revised. Kraepelin created paranoid DP de novo from a division of his early broad delusional syndrome Verrücktheit, distinguishing it from paranoia. Two of these syndromes (catatonic DP and paranoid DP) were present in different forms in his earlier textbook editions, and 1 syndrome (hebephrenic DP) was not. In his 2 prequels, the 3 syndromes were listed together with a brief preface. In the sixth textbook edition, they became "clinical forms" of DP with a lengthy integrative introduction. Much more than in his prequels, in his sixth edition, Kraepelin stitched these 3 syndromes together, emphasizing their shared signs, symptoms, and course. Hebephrenia was the core of Kraepelin's DP concept, while the paranoid subtype fitted least comfortably within his framework. His term dementia was meant in a broad sense consistent with both short-term and rare long-term recoveries. Kraepelin was a pragmatist, not a purist, in his nosologic work and focused both on clinical features and course and outcome. He experimented with various nosologic categories, willing to revise earlier formulations in the light of new data. He was more tentative about his conclusions than many who followed him.

Brain imaging in catatonia: systematic review and directions for future research.

BACKGROUND: Catatonia is a frequent, complex and severe identifiable syndrome of motor dysregulation. However, its pathophysiology is poorly understood. METHODS: We aimed to provide a systematic review of all brain imaging studies (both structural and functional) in catatonia. RESULTS: We identified 137 case reports and 18 group studies representing 186 individual patients with catatonia. Catatonia is often associated with brain imaging abnormalities (in more than 75% of cases). The majority of the case reports show diffuse lesions of white matter, in a wide range of brain regions. Most of the case reports of functional imaging usually show frontal, temporal, or basal ganglia hypoperfusion. These abnormalities appear to be alleviated after successful treatment of clinical symptoms. Structural brain magnetic resonance imaging studies are very scarce in the catatonia literature, mostly showing diffuse cerebral atrophy. Group studies assessing functional brain imaging after catatonic episodes show that emotional dysregulation is related to the GABAergic system, with hypoactivation of orbitofrontal cortex, hyperactivation of median prefrontal cortex, and dysconnectivity between frontal and motor areas. CONCLUSION: In catatonia, brain imaging is abnormal in the majority of cases, and abnormalities more frequently diffuse than localised. Brain imaging studies published so far suffer from serious limitations and for now the different models presented in the literature do not explain most of the cases. There is an important need for further studies including a better clinical characterisation of patients with catatonia, functional imaging with concurrent catatonic symptoms and the use of novel brain imaging techniques.

Use of Electroconvulsive Therapy in Autism.

The mechanism of action of electroconvulsive therapy (ECT) is not fully elucidated, with prevailing theories ranging from neuroendocrinological to neuroplasticity effects of ECT or epileptiform brain plasticity. Youth with autism can present with catatonia. ECT is a treatment that can safely and rapidly resolve catatonia in autism and should be considered promptly. The literature available for ECT use in youth with autism is consistently growing. Under-recognition of the catatonic syndrome and delayed diagnosis and implementation of the anticatatonic treatment paradigms, including ECT, as well as stigma and lack of knowledge of ECT remain clinical stumbling blocks.

Delirious mania as a frequent and recognizable neuropsychiatric syndrome in patients with anti-NMDAR encephalitis.

BACKGROUND: Previous case reports showed that delirious mania could be one of the many neuropsychiatric presentations of Anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE). OBJECTIVE: To evaluate the frequency of delirious mania and its associated factors in ANMDARE. METHOD: A prospective study, including all patients with ANMDARE admitted to the National Institute of Neurology and Neurosurgery of Mexico, from January 2014 to April 2019. The diagnosis of delirious mania was established when diagnostic criteria for mania and delirium were fulfilled simultaneously. RESULTS: 79 patients with definitive ANMDARE were included. Delirious mania was identified in 20 (25.3%) of these patients. Catatonia, psychomotor agitation, disinhibition, impulsivity, and grandiose delusions were significantly associated with delirious mania. Also, a lower frequency of EEG abnormalities, absence of extreme delta brush, and a shorter hospital stay was observed in these patients. CONCLUSION: Delirious mania proved to be a frequent neuropsychiatric presentation of ANMDARE, and its presence should warn the physician about the possibility of this diagnosis. It was mainly associated with higher rates of catatonia, psychomotor agitation, disinhibition, and psychotic symptoms. The lack of recognition of delirious mania as a neuropsychiatric presentation in ANMDARE may be a source of diagnostic and therapeutic errors, as most physicians associate this with bipolar disorder.

Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports.

OBJECTIVE: To ascertain the phenomenological characterisation of catatonia in N-methyl-d-aspartate receptor antibody encephalitis (NMDAr-AbE). METHODS: A systematic review of case reports was undertaken in accordance with PRISMA guidelines. Case reports of NMDAr-AbE containing sufficient information on the cases' clinical presentation and meeting the study's inclusion criteria were selected. Cases were searched for clinical data in keeping with core catatonic signs by applying the screening instrument of the Bush-Francis Catatonia Rating Scale. When two or more core signs were ascertained catatonia was considered to be present. RESULTS: 2645 records were identified through the database search. Following screening and application of eligibility/inclusion criteria 139 articles were selected reporting on 189 individual subjects. Catatonia was present in 60% of these cases. The most prevalent signs were immobility/stupor (70%), mutism (67%), excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and rigidity (30%). Immobility/stupor and excitement co-occurred in the same patient in 33% of cases. CONCLUSION: The phenomenological profile of catatonia in this sample of cases of NMDAr-AbE was characterised by a preponderance of signs in the hypokinetic spectrum. However, excitement often co-occurred in these patients suggesting that fluctuations in catatonic semiology may be frequent.

A Metabolic Brain Pattern Associated With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes substantial neurological disability. Autoantibodies causing encephalitis directed against the neuronal cell surface or synapse are of diagnostic importance giving the possibility of successful immunotherapy. OBJECTIVE: In this study, we aim to provide supporting evidence that brain 18F-FDG-PET may be helpful in identifying likely patterns of regional brain glucose metabolism. METHODS: Thirty-three patients (18 men and 15 women; age range of 17-55 y) with positive NMDA receptor antibody encephalitis that underwent an 18F-FDG-PET imaging examination were prospectively selected and compared with a reference group of 14 brain 18F-FDG-PET scans from healthy volunteers using voxel-based statistical analysis. Clusters of hyper- and hypo-metabolism were reported for the whole sample of patients (FWE-corrected P < 0.05), and uncorrected at P < 0.005 for a group of relapsed patients. RESULTS: Mixed metabolic patterns (focal/bilateral hypermetabolism in the temporal lobe, insula, and cerebellum; associated with severe bilateral hypometabolism in the occipital and parietal lobes) were found. CONCLUSIONS: Our findings suggest that 18F-FDG-PET should be included as an imaging tool when assessing affected patients in the clinical workup to rule out anti-NMDA encephalitis and help determine the most effective treatment.

Going Back to Kahlbaum's Psychomotor (and GABAergic) Origins: Is Catatonia More Than Just a Motor and Dopaminergic Syndrome?

In 1874, Karl Kahlbaum described catatonia as an independent syndrome characterized by motor, affective, and behavioral anomalies. In the following years, various catatonia concepts were established with all sharing the prime focus on motor and behavioral symptoms while largely neglecting affective changes. In 21st century, catatonia is a well-characterized clinical syndrome. Yet, its neurobiological origin is still not clear because methodological shortcomings of hitherto studies had hampered this challenging effort. To fully capture the clinical picture of catatonia as emphasized by Karl Kahlbaum, 2 decades ago a new catatonia scale was developed (Northoff Catatonia Rating Scale [NCRS]). Since then, studies have used NCRS to allow for a more mechanistic insight of catatonia. Here, we undertook a systematic review searching for neuroimaging studies using motor/behavioral catatonia rating scales/criteria and NCRS published up to March 31, 2019. We included 19 neuroimaging studies. Studies using motor/behavioral catatonia rating scales/criteria depict cortical and subcortical motor regions mediated by dopamine as neuronal and biochemical substrates of catatonia. In contrast, studies relying on NCRS found rather aberrant higher-order frontoparietal networks which, biochemically, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This is further supported by the high therapeutic efficacy of GABAergic agents in acute catatonia. In sum, this systematic review points out the difference between motor/behavioral and NCRS-based classification of catatonia on both neuronal and biochemical grounds. That highlights the importance of Kahlbaum's original truly psychomotor concept of catatonia for guiding both research and clinical diagnosis and therapy.

A longitudinal perspective on the pharmacotherapy of 24 adult patients with Phelan McDermid syndrome.

Over the past years, 24 patients with Phelan-McDermid syndrome were carefully investigated with respect to history, somatic and neurologic antecedents, treatment history, behavioural issues, and psychiatric symptoms including possible catatonic features and regression phenomena. Patients were originally referred for specialized diagnosis and treatment advice because of recurrent challenging behaviours along with instable mood. In all, standardized neuropsychiatric examination was performed including assessment of intellectual and adaptive functioning as well as communication and behaviour concerns. Psychiatric diagnoses were actualized in interdisciplinary consultation meetings according to ICD-10 guidelines. The course of disease was periodically monitored with respect to treatment efficacy and psychopathology over a period varying from one to five years. In 18 patients, a deletion encompassing part of or the entire SHANK3 gene was found. All comprised two or more genes in addition to SHANK3. In six patients, a pathogenic variant in this gene was detected. The psychopathological profile of all patients (nine were published before) was characterized by symptoms from the autism and schizoaffective spectrum while in five, periodic catatonic symptoms were also established. In their third decade, four patients with the deletion subtype developed a regression-like gradual decline of functioning. Based on actual psychiatric classification, in 18 patients, a diagnosis of atypical bipolar disorder was established of which symptoms typically started from late adolescence onward. In most patients, treatment with mood stabilizing agents in combination with individually designed contextual measures, and if indicated with the addition of an atypical antipsychotic, resulted in gradual stabilization of mood and behaviour.

A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [-9; +10; +60] and L-LPM [-46; -12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76-100%) and specificity 88% (72-97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.

The Development of Kraepelin's Mature Diagnostic Concept of Catatonic Dementia Praecox: A Close Reading of Relevant Texts.

Through a close reading of texts, this essay traces the development of catatonia from its origination in Kahlbaum's 1874 monograph to Kraepelin's catatonic subtype of his new category of Dementia Praecox (DP) in 1899. In addition to Kraepelin's second to sixth textbook editions, I examine the six articles referenced by Kraepelin: Kahlbaum 1874, Brosius 1877, Neisser 1887, Behr 1891, Schüle 1897, and Aschaffenburg 1897 (Behr and Aschaffenburg worked under Kraepelin). While Brosius and Neisser confirmed Kahlbaum's descriptions, Behr, Schüle, and Aschaffenburg concluded that his catatonic syndrome was nonspecific and only more narrowly defined forms, especially those with deteriorating course, might be diagnostically valid. Catatonia is first described by Kraepelin as a subform of Verrücktheit (chronic nonaffective delusional insanity) in his second to fourth editions. In his third edition, he adds a catatonic form of Wahnsinn (acute delusional-affective insanity). His fourth and fifth editions contain, respectively, catatonic forms of his two proto-DP concepts: Psychischen Entartungsprocesse and Die Verblödungsprocesse. Kahlbaum's catatonia required a sequential phasic course. Positive psychotic symptoms were rarely noted, and outcome was frequently good. While agreeing on the importance of key catatonic signs (stupor, muteness, posturing, verbigeration, and excitement), Kraepelin narrowed Kahlbaum's concept, dropping the phasic course, emphasizing positive psychotic symptoms and poor outcome. In his fourth to sixth editions, as he tried to integrate his three DP subtypes, he stressed, as suggested by Aschaffenburg and Schüle, the close clinical relationship between catatonia and hebephrenia and emphasized the bizarre and passivity delusions seen in catatonia, typical of paranoid DP.

Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.

Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score ≥ 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior.

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

Cingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment.

The catatonic syndrome is an example of a multifactorial neurobehavioral disorder that causes much morbidity and mortality but also has the potential to unlock the mystery of how motivation and movement interact to produce behavior. In this chapter, an attempt is made to understand better the catatonic syndrome through the lens of neurobiology and neuropathophysiology updated by recent studies in molecular biology, genomics, inflammasomics, neuroimaging, neural network theory, and neuropsychopathology. This will result in a neurostructural model for the catatonic syndrome that centers on paralimbic regions including the anterior and midcingulate cortices, as they interface with striatal and thalamic nodes in the salience decision-making network. Examination of neurologic disorders like the abulic syndrome, which includes in its extreme catatonic form, akinetic mutism, will identify the cingulate cortex and paralimbic neighbors as regions of interest. This exploration has the potential to unlock mysteries of the brain cascade from motivation to movement and to clarify catatonia therapeutics. Such a synthesis may also help us discern meaning inherent in this complex neurobehavioral syndrome.