Frontal CSF enlargement in panic disorder: A qualitative CT-scan study

Brain morphology was assessed qualitatively in CT scans of 21 patients with panic disorder and 21 normal control subjects. Patients showed significant bilateral enlargement of frontal cerebrospinal fluid (CSF) spaces. These findings suggest that alterations in brain morphology are involved in the etiology of panic disorder.     

Increased CSF amino acids and ventricular enlargement in schizophrenia: a preliminary study

We found significantly higher levels of cerebrospinal fluid alanine, glycine, leucine, and phenylalanine in schizophrenic patients compared to healthy controls. Ventricular enlargement was present in 4 of 11 schizophrenics, and elevated CSF alanine was highly correlated with ventricular enlargement. The implications of these findings are discussed.     

CSF prostaglandin-E in agoraphobia with panic attacks

Prostaglandins are thought to act as neuromodulators of both central catecholamine and endocrine systems. Abnormalities of these systems have been described in affective disorders, in general, and in agoraphobia with panic attacks, in particular. This study measured basal prostaglandin-E (PGE) cerebrospinal fluid (CSF) levels in 20 patients with agoraphobia with panic attacks and 10 nonpsychiatric controls. In a subgroup of patients and controls, CSF levels of adrenocorticotrophic hormone (ACTH) and corticotropin-releasing factor (CRF) were also measured. There was no significant difference in CSF PGE levels between patients and controls. However, patients with higher depression scores had lower CSF PGE levels. CSF PGE levels tended to correlate with CSF ACTH, but not CSF CRF in the patient group, in general, and in the female patients, in particular. These findings do not support an abnormality in basal CNS PGE production in agoraphobia with panic attacks, but suggest further study of the PGE modulatory effect on the hypothalamic-pituitary-adrenal axis in this disorder.     

CSF hydrodynamics in idiopathic intracranial hypertension: a long-term study.

To examine CSF hydrodynamics, we studied 16 patients with idiopathic intracranial hypertension and 45 control subjects with a constant-pressure infusion method. Fifteen patients had 155 examinations up to 15 years after the onset of disease. In most patients, the disturbances of CSF hydrodynamics persisted for many years. We identified at least two mechanisms for the development of the increased CSF pressure: a rise of sagittal sinus pressure, probably explained by extracellular edema causing partial compression of the major venous sinus (type 1), or a low conductance with a compensatory increase in CSF pressure in order to sustain the bulk flow (type 2).     

Prefrontal cortical thickness in first-episode psychosis: a magnetic resonance imaging study.

BACKGROUND: Findings from postmortem studies suggest reduced prefrontal cortical thickness in schizophrenia; however, cortical thickness in first-episode schizophrenia has not been evaluated using magnetic resonance imaging (MRI). METHODS: Prefrontal cortical thickness was measured using MRI in first-episode schizophrenia patients (n = 17), first-episode affective psychosis patients (n = 17), and normal control subjects (n = 17); subjects were age-matched within 2 years and within a narrow age range (18-29 years). A previous study using the same subjects reported reduced prefrontal gray matter volume in first-episode schizophrenia. Manual editing was performed on those prefrontal segmentations before cortical thickness was measured. RESULTS: Prefrontal cortical thickness was not significantly different among groups. Prefrontal gray matter volume and thickness were, however, positively correlated in both schizophrenia and control subjects. The product of boundary complexity and thickness, an alternative measure of volume, was positively correlated with volume for all three groups. Finally, age and age at first medication were negatively correlated with prefrontal cortical thickness only in first-episode schizophrenia. CONCLUSIONS: This study demonstrates the potential usefulness of MRI for the study of cortical thickness abnormalities in schizophrenia. Correlations between cortical thickness and age and between cortical thickness and age at first medication suggest that the longer the schizophrenic process has been operative, the thinner the prefrontal cortex, although this needs confirmation in a longitudinal study.     

Cortical sulcal enlargement in catatonic schizophrenia: a planimetric CT study.

To determine whether patients with catatonic schizophrenia have specific alterations in brain morphology, internal (ventricles) and external (frontal, temporal, parieto-occipital) components of the cerebrospinal fluid (CSF) spaces were examined morphometrically. Planimetric measurements of computed tomographic (CT) scans from 37 patients with catatonic schizophrenia, 28 patients with hebephrenic schizophrenia, and 39 patients with paranoid schizophrenia, all diagnosed according to DSM-III-R criteria, were compared with separate age- and sex-matched non-psychiatric control groups, respectively. The areas of the frontal sulci, the parieto-occipital sulci, the inter-hemispheric fissure, and the lateral and third ventricles were measured separately for the right and left hemispheres. Catatonic patients showed significant enlargements in almost all CSF spaces, especially in the left fronto-temporal area which, in addition, correlated significantly with illness duration. Hebephrenic patients showed selective enlargements in left temporal and left/right lower frontal cortical sulci, whereas paranoid schizophrenic patients showed no enlargements but significant correlations between left temporal cortical sulcal volume and illness duration. Alterations in temporal cortical areas were present in all three sub-types of schizophrenia. In addition to temporal alterations, hebephrenic schizophrenia was characterised by lower frontal (i.e. orbitofrontal) enlargement. Catatonic schizophrenia, the most severe sub-type with regard to clinical symptomatology and brain pathology, showed fronto-parietal cortical alterations.     

Neuroleptic malignant syndrome: a study of CSF monoamine metabolism.

In 8 cases of typical neuroleptic malignant syndrome (NMS), homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), noradrenaline (NA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in the cerebrospinal fluid (CSF) were assayed during both the active phase of NMS and after recovery. Compared with levels in normal control subjects the levels of HVA were significantly lower in patients with active NMS. This finding supports the central dopamine blockade theory of NMS pathophysiology. In addition, the levels of HVA were significantly decreased after recovery, suggesting that there may be a decreased dopamine metabolism in patients susceptible to NMS. The levels of 5-HIAA in patients with active NMS and after recovery were also significantly lower than those in normal control group, suggesting a relationship between the development of NMS and a disturbance of serotonin metabolism. The levels of NA in patients with active NMS were significantly higher than in normal subjects, and were within normal range after recovery. The levels of MHPG had a tendency to increase in patients with active NMS, compared with levels during recovery. These findings are a result of increased sympathetic nervous system activity in patients with active NMS; however, they are also observed in other disorders and may well reflect the physical stress caused by NMS.     

Prefrontal cortex and insight in schizophrenia: a volumetric MRI study

Previous studies have suggested a relationship between frontal lobe-based neuropsychological functions and insight in schizophrenia. There is some evidence linking both smaller whole brain volume and frontal cortical atrophy to poor insight in this population. We investigated the relationship between total as well as specific prefrontal regional volumes and insight in schizophrenia. Twenty-eight stable outpatients with schizophrenia underwent magnetic resonance imaging scanning and assessment for insight. Insight was measured using the Birchwood self-report Insight Scale and the Expanded Schedule of Assessment of Insight. The whole brain and prefrontal regional (superior frontal, middle frontal, inferior frontal and orbitofrontal) volumes were then manually measured using the Cavalieri method and established criteria. Twenty healthy subjects were also scanned to provide control data for volumetric assessments. Smaller total prefrontal grey matter volume was moderately associated with a lower level of insight into the presence of illness. At the prefrontal sub-regional level, volumes of the superior, inferior and orbitofrontal regions contributed to this relationship, especially in males. It is concluded that smaller prefrontal grey matter volume is associated with poor insight into the presence of illness in stable schizophrenia patients. Future research should examine the association of specific dimensions of insight with frontal as well as non-frontal regional brain volumes.     

Visuo-spatial attention processes in panic disorder with agoraphobia: a pilot study using a visual target discrimination task.

Panic attacks can be observed in a wide range of situations, but most common are those providing complex and unstructured stimulations, suggesting an impairment in attentional processing of visuo-spatial information. This study evaluated agoraphobics' attentional processing of neutral (i.e., not anxiety-provoking) visuo-spatial stimulation. Twelve patients suffering from panic attacks with agoraphobia were compared with 22 normal controls on a computerized visual target discrimination task specifically designed for this study. Psychometric measures assessed the phobic avoidance, the level of depression and anxiety. The numbers of errors and reaction times were analysed with a three-way ANOVA (Group x target modality x number of stimulations). No between-group significant difference was found for the reaction time performance and the mean number of detection errors. However, an interaction effect was observed for this last variable depending on the target modality: agoraphobic patients made fewer omission errors than control subjects when the target was present among distractors, while they made more commission errors when the target was absent. Outcomes are discussed in terms of attentional hyperactivation related to anxiety and perseverative decision process in agoraphobic patients.     

Anti-HIV antibodies in the CSF of AIDS patients: a serological and immunoblotting study.

CSF and serum samples from 16 AIDS patients were tested for the presence of anti-HIV antibodies either by classical serological methods or by an immunoblot technique based on agarose gel isoelectric focusing and transfer of the specific IgG antibodies onto HIV antigens-loaded nitrocellulose sheets. This method enabled the demonstration of an intrathecal synthesis of anti-HIV oligoclonal IgG antibodies, often superimposed on diffuse polyclonal production, in 14 patients. The two negative cases were devoid of neurological signs or symptoms. However, two patients classified in stage II of the disease (asymptomatic infection) displayed an intrathecal synthesis of anti-HIV antibodies.     

Ventriculogastrostomy, an alternative means for CSF diversion: a preliminary study.

The feasibility of gastric CSF diversion in the management of hydrocephalus is evaluated in laboratory and clinical settings. A technique for ventriculogastrostomy is described and evaluated initially in 8 mongrel dogs. All distal shunts remained patent to the time of sacrifice. None of the animals exhibited leakage of gastric contents around the tubing. Cultures of the components of the shunting system and gastric mucosa were sterile. Clinical evaluation in a 3 week-old child is discussed. The trial was terminated at 3 weeks postsurgery because of the occurrance of an E. coli ventriculitis which was considered to be secondary to a preoperative conjunctivitis in which the organism was identical. It is concluded that there is good experimental evidence to support the concept of effectiveness of ventriculogastrostomy in the treatment of selected cases of hydrocephalus.     

Developing a U.K. protocol for collaborative care: a qualitative study

OBJECTIVE: This study aimed to explore the views of stakeholders including patients, general practitioners (GPs) and mental health workers on the feasibility, acceptability and barriers to a collaborative care model for treatment of depression within the context of U.K. primary health care. METHOD: We used semistructured interviews and focus groups with a purposive sample of 11 patients and 38 professionals from a wide selection of primary and secondary care mental health services, as well as framework analysis using a "constant comparative" approach to identify key concepts and themes. RESULTS: Regular contact for patients with depression is acceptable and valued by both patients and professionals. However, patients value support, whereas professionals focus on information. To be acceptable to patients, contacts about medication or psychosocial support must minimize the potential for patient disempowerment. The use of the telephone is convenient and lends anonymity, but established mental health workers think it will impair their judgments. While patients merely identified the need for skilled case managers, GPs preferred established professionals; however, these workers did not see themselves in this role. All involved were cautious about deploying new workers. Additional barriers included practical and organizational issues. CONCLUSIONS: Although a telephone-delivered mix of medication support and low-intensity psychological intervention is generally acceptable, significant issues to be addressed include the values of the current mental health workforce, fears about new workers' experience and competence, the balance of face-to-face and telephone contacts and case manager education in nonspecific skills necessary to develop a therapeutic alliance, as well as the knowledge and skills required for education, medication support and behavioral activation. Qualitative research can add value to careful modeling of collaborative care prior to international implementation.     

Otoneurological examination in panic disorder and agoraphobia with panic attacks: a pilot study

A battery of vestibular and audiological tests was administered to eight patients with panic disorder and 13 patients with agoraphobia and panic attacks, all of whom experienced dizziness during their panic attacks. Positional or spontaneous nystagmus was present in 67% of the subjects. Abnormal responses were found in caloric testing (56%), rotational testing (35%), and posturography (32%). Pure tone audiograms were abnormal in 26% of the subjects and acoustic reflexes were abnormal in 44% of the subjects. Six of eight patients tested had an abnormal brainstem auditory evoked potential. The possible importance of the findings and their implications for further research are discussed.     

Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring

Our objective was to evaluate parental risk factors for pediatric-onset panic disorder/agoraphobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who had a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood.     

IgG paraproteinemias: a comparative CSF and serum study

In 10 neurologic patients routine isoelectric focusing of CSF and serum revealed monoclonal IgG paraproteinemia (3 multiple myelomas and 7 benign monoclonal gammopathies). Quantitative protein study showed blood-brain barrier damage in 7 out of 10 patients; 2 patients had intrathecal synthesis of IgG measurable by Reiber's formula. Each case showed identical monoclonal IgG pattern in CSF and serum at isoelectric focusing and immunofixation. We suppose that monoclonal IgG detectable in the CSF usually derive from the serum across the intact or damaged barrier. The occurrence of quantifiable intrathecally synthesized IgG in 2 patients, both with skeletal lesions close to the subarachnoid spaces, and the identical patterns of IgG in CSF and serum suggest that tumoral plasma cells secrete monoclonal IgG into blood and CSF from the bone location.     

Relationship between panic disorder and agoraphobia. A family study

A family study of patients with agoraphobia (n = 40), panic disorder (n = 40), and nonanxious controls (n = 20) showed that the morbidity risk for panic disorder was increased among the relatives of agoraphobics (8.3%) and the relatives of patients with panic disorder (17.3%). The morbidity risk for agoraphobia was also increased among the relatives of agoraphobics (11.6%) but not the relatives of panic disorder patients (1.9%). Male relatives of agoraphobics were shown to be at higher risk for alcohol disorders (30.8%). No greater risk for primary affective disorders was found among the relatives of agoraphobic or panic disorder patients or among the relatives of probands with secondary depression compared with relatives of probands without secondary depression. Probands and relatives with agoraphobia reported an earlier onset of illness, more persistent and disabling symptoms, more frequent complications, and a less favorable outcome than probands and relatives with panic disorder. The findings suggest that agoraphobia is a more severe variant of panic disorder. They also lend support to the separation between anxiety disorders and affective disorders.     

Vestibular rehabilitation for patients with agoraphobia and vestibular dysfunction: a pilot study

This study examined whether physical therapy with vestibular rehabilitation exercises would benefit patients with agoraphobia and vestibular dysfunction. Nine patients went through a 2-week no-treatment baseline phase, a 4-week behavioral treatment phase focusing on self-directed exposure, and an 8-12-week vestibular rehabilitation phase (weekly sessions). On the main outcome measure, clinical global impressions (CGI) ratings of severity, behavioral treatment was accompanied by a reduction in severity (effect size d=0.8; P<.10). On the supplementary measures, the Hamilton Anxiety Scale (Hamilton-A) and the Chambless Mobility Inventory (MI), no significant improvements were noted. After vestibular rehabilitation therapy, further improvement occurred in CGI severity (d=0.65; two-tailed P<.10), and significant improvements occurred in the supplementary measures. The physical therapist identified motion-induced dizziness and disturbances in balance in most patients. These improved with rehabilitation. Although the results can be attributed to other explanations, they are not inconsistent with the hypothesis that vestibular dysfunction maintains agoraphobic symptoms in some patients.