Brain Motor Region Diffusion Tensor Imaging in Patients with Catatonic Schizophrenia: A Case-Control Study.

BACKGROUND: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce. OBJECTIVES: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia. METHODS: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level. RESULTS: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas. CONCLUSIONS: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

[Catatonia and neuroleptic malignant syndrome in view of a psychopathological and pathophysiological overlap: a brief review]. / Katatónia és neuroleptikus malignus szindróma a pszichopatológiai és patofiziológiai átfedések tükrében: rövid összefoglaló tanulmány.

Catatonia was first described in the 19th century as a syndrome with motor, affective and behavioral symptoms. During the 20th century it was rather regarded as a rare motoric manifestation of schizophrenia and that classification has almost resulted in the disappearance of catatonia among patients outside of the schizophrenia spectrum. With the introduction of neuroleptics, the incidence of catatonic schizophrenia also declined which was attributed to effective treatment. Simultaneously, neuroleptic malignant syndrome was described, which shows many similarities with catatonia. Recently, several researchers suggested a common origin of the two disorders. In this paper we review case reports of the last five years, in which both neuroleptic malignant syndrome and catatonia had emerged as a diagnosis. Additionally, based on the relevant literature, we propose a common hypothetical pathomechanism with therapeutic implications for the two syndromes. Besides underlining the difficulties of differential diagnosis, the reviewed cases demonstrate a transition between the two illnesses. The similarities and the possible shifts may suggest a neuropathological and pathophysiological overlap in the background of the two syndromes. Electroconvulsive therapy and benzodiazepines seem to be an effective treatment in both syndromes. These two treatment approaches can be highly valuable in clinical practice, especially if one considers the difficulties of differential diagnosis.

[Long-term dyskinetic remissions in shift-like schizophrenia].

The study sample included 32 patients with long-term remissions (from 5 to 33 years) developed after episodes of shift-like schizophrenia with catatonic disorders. All patients showed a good social and professional adjustment. This type of remissions was designated as "dyskinetic" due to the predomination of motor disturbances, microcatatonic symptoms of stupor and excitement. The diskinetic remission was characterized by stereotype urge to act, psychomotor passivity and decompensation "catatonic reactions". Two types of dyskinetic remission were singled out: hyper- and hypokinetic. Their psychopathological structure was defined by the hypersthenic defect including "the monotonous activity and the rigidity of the affect" in the first type and "irritable asthenia" in the second one. The hypothesis was developed: catatonic symptoms included to the structure of mentioned types of defect.

[Dissolution of the wakefulness-sleep cycle in patients with catatonic form of schizophrenia].

Polysomnograms of two patients with catatonic form of schizophrenia of different duration of the disease were recorded and analyzed. Pronounced disorders of the wakefulness-sleep cycle (WSC) were revealed. Apart from differences connected with duration of the disease and treatment with corresponding medications, there were detected the general features indicating dissolution of the central nervous system and the very wakefulness-sleep cycle. A certain similarity of the found WSC disturbances with the earlier shown WSC disturbances in rats with predisposition to catalepsy was noted. The conclusion is made about domination of diencephalic influences over the telencephalic one in the studied patients.

Does catatonic schizophrenia improve faster with electroconvulsive therapy than other subtypes of schizophrenia?

OBJECTIVE: Electroconvulsive therapy (ECT) is generally recommended for treating catatonic schizophrenia. Non-catatonic schizophrenia patients also receive ECT. We compared the speed of response to ECT among patients with catatonic and other subtypes of schizophrenia. METHODS AND MATERIALS: Consecutive schizophrenia patients referred for ECT within 3 months of starting antipsychotic treatment were studied (19 with catatonic and 34 with non-catatonic schizophrenia). Nurse's Observation Scale for Inpatient Evaluation (NOSIE-30) and Clinical Global Impression (CGI) were used to rate improvement. Referring psychiatrists stopped ECTs based on clinical impression of improvement. Total number of ECTs was taken as an indirect measure of speed of response. NOSIE-30 scores were compared using repeated measures analysis of variance. RESULTS: Catatonic schizophrenia patients required significantly fewer ECTs to achieve clinically significant improvement. There was a significant group x occasion effect in NOSIE scores, suggesting faster response to ECT in the catatonia group (F=41.6; P<0.001). Survival analysis suggested that patients with catatonic schizophrenia required significantly fewer ECTs (one less session on an average) to achieve clinical improvement (Log-rank statistic =5.31; P=0.02). CONCLUSIONS: Catatonic schizophrenia responds faster to ECT than non-catatonic schizophrenia. However, the magnitude of the difference is modest.

Increased left prefrontal activation during staring/mutism episodes in a patient with resistant catatonic schizophrenia: a near infrared spectroscopy study.

OBJECTIVE: To present the first near infrared spectroscopy (NIRS) study of a patient with resistant catatonic schizophrenia during residual episodes of catatonia-related symptoms. BACKGROUND: Functional imaging studies generally point to a decreased cortical activation in catatonic patients, with the notable exception of increased orbitofrontal/medial prefrontal activity elicited by negative stimuli. METHODS: Cortical activity of the left anterior prefrontal area was recorded with a Techen 4 x 4 NIRS apparatus. Four episodes of staring/mutism were recorded and averaged. Compared with normal activity, these episodes were characterized by increased cortical activation. CONCLUSIONS: Within its methodologic limitations, the present observation suggests that increased anterior prefrontal activation in catatonic patients is not specific to negative stimuli. Known functions of the anterior prefrontal cortex such as self monitoring, reallocation of attention, or conflict resolution might underlie these findings. These also attest to the potential of NIRS for functional imaging of vulnerable subjects.

Deficit in decision making in catatonic schizophrenia: an exploratory study.

Catatonic schizophrenia can be distinguished from paranoid schizophrenia by prominent behavioral and motor anomalies. As demonstrated in recent imaging studies, behavioral symptoms may be related to dysfunction in the ventral prefrontal cortex. However, the neuropsychological correlates of ventral prefrontal cortical dysfunction remain unclear. In an exploratory study, we investigated eight patients with catatonic schizophrenia and compared them with 19 patients with paranoid schizophrenia and 26 healthy subjects. The Iowa Gambling Task (IGT) and the Object Alternation Task (OAT) served as measures of ventral prefrontal cortical function. In addition, other prefrontal cortical tests such as a visual working memory task, a Go-NoGo task, and the Wisconsin Card Sorting Test, as well as attentional tasks, were included in the test battery. Catatonic patients showed significant deficits in the IGT characterized by an inability to shift from the initial preference for high-risk cards to a more advantageous strategy with low-risk cards. Moreover, catatonic patients showed significant deficits in the OAT. In conclusion, our preliminary results suggest a specific deficit in catatonic schizophrenia in those neuropsychological measures that are associated with ventral prefrontal cortical function.

The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain.

The human MLC1 gene (also known as KIAA0027 and WKL1) and its murine orthologue (Mlc1) encode a putative transmembrane protein expressed primarily in brain. Recessive mutations within human MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), whereas a missense mutation resulting in a methionine substitution within a transmembrane leucine string of MLC has been implicated in catatonic schizophrenia in a large pedigree. To gain insight into the function of the MLC protein and to elucidate the pathophysiology of these severe neurodegenerative disorders, information on the cellular and regional distribution of the murine Mlc1, as well as the developmental pattern of Mlc1 expression in brain, is required. Using in situ hybridization (ISH), Mlc1 mRNA was exclusively detected in glial cells of the adult murine brain, such as astrocytes, Bergmann glia, and ependymal cells. ISH, Northern blot analysis, and quantitative real-time polymerase chain reaction (PCR) demonstrated that Mlc1 mRNA is broadly distributed in the adult mouse brain, with highest concentrations of expression in the cerebellum and olfactory bulb. Furthermore, differential expression patterns during brain development were revealed. Overall brain Mlc1 mRNA concentrations exhibited a substantial increase in the perinatal period reaching adult concentrations at postnatal day 5. At the cellular level, highest Mlc1 expression was found during the pre- and perinatal period in multipotential neural precursor cells, especially in the subventricular zone of the lateral ventricle, whereas in adulthood highest Mlc1 mRNA concentrations were revealed in Bergmann glia cells. Because the temporal expression profile of Mlc1 indicates that, in contrast to developing and mature astrocytes, oligodendrocytes are devoid of Mlc1 expression, white matter tract abnormalities observed in these disorders may result from a primary astrocytic defect. Detailed information on Mlc1 expression in brain is likely to lead to a better understanding of Mlc1 involvement in the pathogenesis of both MLC and catatonic schizophrenia.

Esquizofrenia catatónica, complicaciones médicas asociadas e indicación de terapia electroconvulsiva: a propósito de un caso clínico / Catatonic schizophrenia: associated medical complications and indication for electroconvulsive therapy. A case report

El diagnóstico de catatonía, como subtipo de esquizofrenia, se basa en unos criterios diagnósticos clínicos definidos. No obstante, no existe una explicación fisiopatológica para este proceso, que desde su origen se describió como de base cerebral, llegando a plantearse la catatonía como un síndrome donde diversas enfermedades psiquiátricas y médicas podrían estar implicadas. Cuando el estudio se centra en ésta como parte de las esquizofrenias, se observa un descenso llamativo en su diagnóstico. Resulta evidente la gravedad de estos procesos, presentando con frecuencia complicaciones médicas que ponen en grave riesgo vital al paciente. La utilización en estos casos de terapia electroconvulsiva (TEC) debe ser de primera elección, no sólo por la magnitud clínica, sino por las complicaciones médicas asociadas y la imposibilidad, en muchos casos, del tratamiento con psicofármacos. A continuación se presenta un caso clínico de episodio catatónico en paciente de edad avanzada con esquizofrenia crónica, donde las complicaciones médicas asociadas hicieron de la TEC la indicación primordial. (AU)

Inverse relation between stimulus intensity and seizure duration: implications for ECT procedure.

A retrospective analysis of the effects of electroconvulsive therapy (ECT) was performed for two groups of 11 patients matched according to age (mean age, 52 years), sex, and diagnosis. Group 1 received ECT according to the age-dose protocol; group 2 was treated according to the titration method. A higher dose relative to the seizure threshold appeared to shorten the seizure duration. At the first treatment, the correlation between stimulus intensity and seizure duration was negative. In the titration group, the initial mean charge of 91 mC resulted in a seizure duration of 51 s, whereas in the age-dose group the seizure duration of 31 s was significantly shorter despite a higher mean charge of 312 mC. Seizure duration decreased during the ECT course in the group treated first at low dose (titrated) and then at 2.5 times the initial threshold. High stimulus intensity represented adequate treatment, although it produced short seizures. Thus, seizure duration proved to be an unreliable guideline for effective treatment. Furthermore, focus on seizure duration led to frequent high-dose restimulation in the elderly. The titration method obviates inadequate or excessive charges because the seizure threshold must first be determined.

Prevalence of obsessive-compulsive disorder in schizophrenia and significance of motor symptoms.

To investigate the differences between schizophrenic subjects with and without obsessive-compulsive disorder (OCD), the authors systematically assessed 76 schizophrenic subjects for OCD. Subjects with and without OCD were then compared with regard to motor symptoms, including catatonia, and several measures of psychopathology. Treatment strategies were evaluated retrospectively. The 12 subjects with OCD (15.8%) had more motor symptoms, including catatonia, than non-OCD schizophrenic subjects. Some differences were found with regard to psychopathological symptoms. Treatment strategies also differed in the two groups. The high prevalence of motor symptoms in these subjects supports the hypothesis of a basal ganglia-frontal lobe connection linking OCD with schizophrenia.

Reduced activation and altered laterality in two neuroleptic-naive catatonic patients during a motor task in functional MRI.

BACKGROUND: Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). METHODS: Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). RESULTS: Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. CONCLUSIONS: In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Gender differences and age of onset in the catatonic subtypes of schizophrenia.

In a family study involving 139 probands with chronic DSM-III-R schizophrenia, catatonic type, 83 probands met the criteria for periodic catatonia and 56 probands those for systematic catatonia according to Leonhard. In the systematic catatonias, we found a low morbidity risk of 4.6% in first-degree relatives, an early age at first hospitalization and a high prevalence of affected males. In the light of our recent report of an association between maternal gestational infection and systematic schizophrenia, male fetuses exposed to midgestational infection seem to be particularly at risk of developing systematic catatonia. Periodic catatonia with a family morbidity risk of 26.9% affected both genders with equal frequency and showed no age-at-onset differences between the genders. We found a moderate inverse relationship between early-onset probands and an increased risk in relatives of 24.1% compared to 17.8% in late-onset probands. Our findings substantiate the hypothesis that periodic catatonia is a clinically homogenous disorder with a major gene effect and an age at onset which is to a large extent genetically determined.

[Electroconvulsive therapy in clinical practice]. / Die Elektrokonvulsionstherapie in der klinischen Praxis.

Between September 1st, 1994, and the end of August, 1995, 3% of all inpatients (21 of 731) were treated with electroconvulsive therapy (ECT) at the Department of General Psychiatry at the University Hospital for Psychiatry in Vienna. These patients suffered from psychotic and/or therapy-resistant depression (n = 15), therapy-resistant schizoaffective psychosis (n = 3), and catatonic schizophrenia (n = 3). ECT was administered in short-time anaesthetised and muscle relaxed patients. On average, each patient was treated with ECT on 9 non-consecutive days. As a rule, electrodes were placed unilaterally over the non-dominant hemisphere at the beginning. In four cases electrodes were placed bifronto-temporally. To be considered as effective the seizure had to last for at least 25 s. In shorter seizure duration ECT was repeated up to a maximum of three times in one session. With this procedure a reduction in clinical global impressions of -3.7 points was achieved in ECT-treated patients, who had been considered to be "severely" to "most severely" ill according to CGI before starting ECT. ECT proved to be effective for treating severe depression and catatonic schizophrenia, with only minor and reversible side effects. For establishing a favorable relation between good clinical outcome and remarkable few side effects, the following factors seem to be of importance, in accordance with the literature: (1) application of biphasic short-impulse stimuli in anaesthetised and muscle relaxed patients; (2) measurement of static impedance to avoid high skin impedance and short circuits. (3) at the beginning of each ECT series unilateral electrode placement over the non-dominant hemisphere; (4) ECT three times weekly on non-consecutive days.

Regional cerebral blood flow in catatonic schizophrenia.

Single photon emission computed tomography (SPECT) with 123I-iodoamphetamine (IMP) as tracer was used to study regional cerebral blood flow (rCBF) distribution in six patients with the catatonic subtype of schizophrenia (DSM-III-R). IMP-SPECT imaging revealed a significant reduction of rCBF in the parietal lobes of both hemispheres. Three-dimensional reconstruction of the SPECT images identified the superior region of the frontoparietal lobe as the most severely affected region. The pattern of rCBF deficits observed in catatonic schizophrenia differs markedly from that seen in 13 patients with other subtypes of schizophrenia and 7 normal control subjects. These observations indicate that parietal lobe dysfunction may be an important component in the pathology of the catatonic subtype of schizophrenia.

Changes in P300 latency and amplitude in schizophrenic patients and healthy controls during the examination.

In 30 schizophrenic patients (sixteen of the paranoid subtype, 14 of the nonparanoid) and healthy controls (n = 30) event-related potentials were obtained with a somatosensory reaction-time (RT) version of the "oddball paradigm" by stimulating the right (first run) and the left (second run) median nerve. Variations of P300 amplitude and latency and of RT within the average (30 trials) were studied by fractionating off-line the original averages in three subaverages. After stimulation of the right median nerve oscillations on P300 amplitude and latency were observed. After stimulation of the left median nerve there was a trend toward a decrease of the P300 amplitude that reached significance at the electrode P3 for patients (p = 0.014) and at the electrode P4 for controls (p = 0.025). The P300 latency showed variations for patients and controls. The mean-RT was prolonged across the subaverages only for schizophrenics, reaching significance after stimulation of the right median nerve. Paranoid and nonparanoid schizophrenic patients showed similar results on P300 and RT parameters across the subaverages. These results are discussed in terms of the influence of motivation and task involvement on the P300 amplitude. These could be unspecific factors that account for the habituation of the P300 along the examination.

[Use of cranio-cerebral hypothermia among the complex resuscitation measures in mental disorders]. / Primenenie kraniotserebral'noi gipotermii v komplekse reanimatsionnykh meropriiatii pri psikhicheskikh zabolevaniiakh.

Craniocerebral hypothermia was employed in multimodality treatment of 10 patients with hypertoxic schizophrenia and 60 patients with intoxication psychoses, the clinical picture of which was characterized by increasing hypoxia and edema-swelling of the brain. Hypothermia was made to a cerebral temperature of 28-30 degrees C for 4-6 hours in the presence of the neurovegetative blockade. The data obtained attest to a high therapeutic efficacy of craniocerebral hypothermia.

[Disorders of pain perception in schizophrenia]. / Gestörtes Schmerzempfinden bei Schizophrenie.

Starting from a case of marked pain insensitivity in a patient suffering from catatonic schizophrenia we state in this paper that analgesia seems to be an ubiquitous phenomenon which is not only caused by physical disorders of the central nervous system. Different models of interpretation as to be found in scientific literature are reviewed. On the basis of today's physiological knowledge, five hypotheses on causal explanation of pain insensitivity in schizophrenics are discussed: Hypalgesia and analgesia are an expression of motorial inability to react; a consequence of a disorder of consciousness; an analgetic effect of neuroleptic drugs; a basic deficit in schizophrenia and; a result of a disturbed psycho-physiological development.