Physiologic instability in panic disorder and generalized anxiety disorder.

BACKGROUND: Because panic attacks can be accompanied by surges in physiologic activation, we tested the hypothesis that panic disorder is characterized by fluctuations of physiologic variables in the absence of external triggers. METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Electrodermal, cardiovascular, and respiratory measures were analyzed using complex demodulation to quantify variability in physiologic indices. RESULTS: Both patient groups reported equally more anxiety and cardiac symptoms than control subjects, but certain other somatic symptoms, including breathlessness, were elevated only in panic disorder patients. Mean end-tidal pCO(2) and respiratory rates were lower, and tidal volume and the number of sighs were higher in panic disorder patients than control subjects. Neither cardiovascular (heart rate, arterial pressure, cardiac output), nor electrodermal instability including sighs distinguished the groups; however, tidal volume instability was greater in panic disorder than generalized anxiety disorder patients or control subjects. Several other respiratory measures (pCO(2), respiratory rate, minute volume, duty cycle) showed greater instability in both patient groups than in control subjects. CONCLUSIONS: Respiration is particularly unstable in panic disorder, underlining the importance of respiratory physiology in understanding this disorder. Whether our findings represent state or trait characteristics is discussed.

Characteristics of sighing in panic disorder.

BACKGROUND: Sighs, breaths with larger tidal volumes than surrounding breaths, have been reported as being more frequent in patients with anxiety disorders. METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Respiratory volumes and timing were recorded with inductive plethysmography and expired pCO(2), from nasal prongs. RESULTS: Panic disorder patients sighed more and had tonically lower end-tidal pCO(2)s than control subjects, whereas generalized anxiety disorder patients were intermediate. Sighs defined as >2.0 times the subject mean discriminated groups best. Sigh frequency was more predictive of individual pCO(2) levels than was minute volume. Ensemble averaging of respiratory variables for sequences of breaths surrounding sighs showed no evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in any group. Sigh breaths were larger in panic disorder patients than in control subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels as quickly in panic disorder patients as in control subjects. CONCLUSIONS: Hypocapnia in panic disorder patients is related to sigh frequency. In none of the groups was sighing a homeostatic response. Panic disorder patients show less peripheral chemoreflex gain than control subjects, which would maintain low pCO(2) levels after sighing.

[The oral vitamin E tolerance test--an attempt at standardization]. / Der orale Vitamin-E-Belastungstest--Versuch einer Standardisierung.

Chronic vitamin E deficiency causes various neurological symptoms such as cerebellar ataxia, hypoesthesia, areflexia, pigmentary retinopathy, nystagmus and muscle weakness. This is commonly caused by malabsorption of vitamin E, which is either a result of malabsorption of fat or occurs as an isolated vitamin E deficiency. The oral vitamin E tolerance test is suitable for the assessment of vitamin E reabsorption and elimination. However, standardised normal parameters have not yet been defined. We investigated 61 healthy individuals aged 18-70 years (mean age, 45.0 years). Each person involved in the trial received 100 IU of all-rac-alpha-tocopherol in 200 millilitres of whole milk. The vitamin E in the serum was then analysed 0, 3, 6, 9, 12, 24, 36, 48, 60, 72 hours after vitamin E was given, using high pressure liquid chromatography. The ratio of vitamin E to the sum of cholesterol and triglycerides was calculated. The 90% CI for the ratio of serum vitamin E to the sum of cholesterol plus triglycerides at the indicated time points was: t = 0 h: 2.0-6.3 micrograms/mg, t = 6 h: 4.2-15.3 micrograms/mg, t = 12 h: 3.0-13.0 micrograms/mg, t = 24 h: 3.8-14.4 micrograms/mg, t = 36 h: 2.9-10.5 micrograms/mg, t = 72 h: 2.1-8.7 micrograms/mg. The serum concentration of vitamin E correlated predominantly with the sum of cholesterol and triglycerides (r = 0.73). The ratio of these parameters is therefore most suitable for diagnosing vitamin E deficiency without relying on false normal serum vitamin E concentrations as a result of abnormally high serum lipid concentrations.

Shared psychotic disorder in delusional parasitosis.

Delusional parasitosis (DP) is associated in 5-15% with shared psychotic disorder (SPD). Little systematic information is available about this particular aspect of the syndrome. A thorough review of all published cases with DP was carried out. 68 case histories of SPD were identified (5.67%). The data of these patients were compared with those of their inducers (n = 44) and with the data of DP patients, who did not transfer their delusional beliefs to others (n = 1,155). Approximately 30% of the psychotic dyads were reported from public health departments. The sex ratio was balanced in the SPD group, but showed a clear preponderance of females in the other two groups. SPD patients and their inducers reported more frequently visual illusions or hallucinations and located the animals correspondingly upon the surface of the skin. No diagnostic differences were found between the inducers and those who had DP but did not induce SPD in others. Albeit 50% of the SPD patients did not receive any treatment except separation from the inducer, the remission rate in this group was 93%.

Voluntary breath holding in panic and generalized anxiety disorders.

OBJECTIVE: Because breath holding causes arterial pCO2 to increase, we used it to test the hypothesis that in panic disorder (PD) a biological suffocation monitor is pathologically sensitive. METHOD: Nineteen patients with PD, 17 with generalized anxiety disorder (GAD), and 22 normal controls took deep breaths on signal and held them until a release signal was given 30 seconds later. This was repeated 12 times separated by 60-second normal breathing periods. RESULTS: PD patients reported having had in the past more symptoms of shortness of breath when anxious, and more frequent frightening suffocation experiences than the other groups. However, increases in self-rated anxiety between periods of normal breathing and periods of breath holding were similar in all three groups. Skin conductance, blood pressure, and T-wave amplitude reactions to breath holdings were also similar, but heart rate acceleration upon taking a deep breath was greater in GAD patients. Before and after individual breath holdings, end-tidal pCO2 was lower in PD patients than in normal controls; GAD patients were intermediate. Inspiratory flow rate did not differ between groups. CONCLUSIONS: Our physiological results provide no direct support for an overly sensitive suffocation alarm system in PD. Lower pCO2 may be due to anxiety causing hyperventilation in patients prone to panic.

Autonomic instability during relaxation in panic disorder.

The ability to relax was assessed in 14 patients with panic disorder (PD) and 15 non-anxious control subjects for 10 min. Before and after relaxation, subjects performed a standardized activating task of talking continuously for 4 min. The fractional decline in reported anxiety, tension, and alertness between the first talking period and the relaxation minimum did not differ between groups, although absolute levels of anxiety and tension were higher for PD patients. The fractional decline in skin conductance between the first talking period and the last minute of relaxation was less for PD patients than control subjects, while their increase in skin temperature was greater. Skin conductance showed a linear decline over the logarithm of relaxation time, the slope of which was less steep for PD patients. Goodness of fit of skin conductance over log time was also significantly poorer for PD patients. Heart rate levels or slopes did not differ between groups. Autonomic differences between PD and control subjects were largely due to six patients who reported having panic attacks during the test and higher pretest anxiety levels. In conclusion, indicators of relaxation were inconsistent. Skin conductance suggested autonomic instability during quiet sitting in patients who panic or who are prone to panic.

[Schizophrenia-like symptoms in the Westphal-Strümpell variation of Wilson disease]. / Schizophrenieähnliche Symptomatik bei der Westphal-Strümpell-Verlaufsform des Morbus Wilson.

Wilson's disease is a rare, autosomal recessive disorder of copper metabolism due to low serum ceruloplasm, resulting in increased copper deposition, especially in the liver and basal ganglia in the brain. The pseudosclerotic type of Wilson's disease, also known as the Westphal-Strümpell form, is distinguished by positional tremor, ataxia and dysarthria as the main symptoms. We use the example of a 23-year-old patient whose neurological symptoms were preceded by a long history of a schizophrenic-like disorder. Clinical symptoms are presented. MRI, SPECT and PET images are illustrated. Therapy and outcome are discussed.

Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA.

In several vertebrate species, Borna disease virus (BDV), the prototype of a new group of animal viruses, causes central nervous system disease accompanied by diverse behavioral abnormalities. Seroepidemiological data indicate that BDV may contribute to the pathophysiology of certain human mental disorders. This hypothesis is further supported by the detection of both BDV antigens and BDV RNA in peripheral blood mononuclear cells (PBMCs) of patients with psychiatric disorders and the isolation of BDV from such PBMCs. Here we describe serological and molecular epidemiological studies on psychiatric patients and healthy individuals from the area of Homburg, Germany. Using a novel Western blot (immunoblot) assay, we found a BDV seroprevalence of 9.6% among 416 neuropsychiatric patients, which is significantly higher than the 1.4% found among 203 healthy control individuals. Human sera displayed a prominent immunoreactivity against the virus nucleoprotein, the p40 antigen. Reverse transcriptase-mediated PCR analysis of RNA extracted from PBMCs of a subset of 26 of the neuropsychiatric patients revealed that 50% were BDV RNA positive. Three of the 13 BDV RNA-positive patients also had BDV-positive serology, whereas one patient with serum antibodies to BDV p40 antigen did not harbor detectable BDV RNA in PBMCs. BDV p40 and p24 sequences derived from human PBMCs exhibited both a high degree of inter- and intrapatient conservation and a close genetic relationship to animal-derived BDV sequences.

Significant reversibility of alcoholic brain shrinkage within 3 weeks of abstinence.

Chronic alcoholism is often associated with brain shrinkage or atrophy. During recent years, it has been demonstrated that this shrinkage is, at least in part, reversible when abstinence is maintained. There are different hypotheses concerning the mechanisms for this reversibility, but many questions are still open. Especially the time conditions for these reversible changes are subject of discussion. Twenty-eight male patients with severe alcohol dependence were investigated in a computed tomographic study at the beginning of abstinence and 3 weeks later. Planimetric evaluation of 5 selected slices revealed a significant decrease in liquor areas and an increase of brain volume. The densitometric analysis showed an increase in brain tissue density. In a multiple regression approach it was shown that the reversibility was mostly influenced by the age of the patients. Our results support neither the hypothesis of an increase in brain water as the most important principle for reversibility in alcoholic brain shrinkage nor the hypothesis of augmented dendritic growth. Other mechanisms like reduced (during chronic intoxication) and normalized (during abstinence) cerebral hemoperfusion have to be considered as possible mechanisms for the reversibility of alcoholic brain shrinkage.

A seizure, and electroencephalographic signs of a lowered seizure threshold, associated with fluvoxamine treatment of obsessive-compulsive disorder.

A 38-year-old patient with severe obsessive-compulsive disorder received fluvoxamine in a clinical study. Psychometric ratings showed marked clinical improvement in the third week of fluvoxamine administration, but after 8 weeks, at a dose of 300 mg per day, he suffered a grand mal seizure after drinking a glass of beer (0.2 liter). He had no history of previous epileptic seizures. Careful neurological evaluation including computer tomography and magnetic resonance imaging of the brain revealed no signs of acute disease. EEG before the fit did not show epileptiform activity; after the fit, spikes and spike-wave complexes appeared, which disappeared upon discontinuation of fluvoxamine. Since his obsessive-compulsive symptoms had responded well to fluvoxamine and worsened after its discontinuation, the drug was cautiously reintroduced. Improvement of the obsessive-compulsive symptoms was observed again, but spikes and spike-wave complexes reappeared at a dose of 50 mg per day. Under anticonvulsant treatment with carbamazepine, fluvoxamine was increased to 100 mg per day. No seizures occurred during a follow-up to two years.

100 years of delusional parasitosis. Meta-analysis of 1,223 case reports.

Delusional parasitosis (DP) is mostly described in single cases or small samples. Data on epidemiology, nosological classification, therapy and course are therefore difficult to interpret. A thorough literature review is recommended to delineate common features of the syndrome. All case reports concerning DP (except toxic forms) were collected and analyzed according to a standardized protocol. DP is a disorder which may occur in every period of life but is much more frequent in older subjects. Sex differences with a predominance of females increase with age. Mean duration of delusion was 3.0 +/- 4.6 years (median: 1 year). Social isolation seems to be more a premorbid feature than a secondary phenomenon related to the delusion. Diagnostic classification revealed a high proportion of so-called 'pure' forms ('delusional disorders' in DSM-III-R or ICD-10) but the syndrome was also reported in schizophrenia, affective or organic psychosis or even as a neurotic symptom. Frequency of induced DP can be estimated between 5 and 15%. Course of DP is not so unfavorable as commonly thought; in about half the patients a full remission was described during the observation period or at catamnesis. Short preclinical courses may indicate better outcome. Comparing the patients of the prepsychopharmacological era (before 1960) with those after, the rate of full remissions increased from 33.9 to 51.9%.

The pattern of regional cerebral blood flow during alcohol withdrawal--a single photon emission tomography study with 99mTc-HMPAO.

Cerebral blood flow was investigated during alcohol withdrawal in 15 male alcoholics by single photon emission computerized tomography with 99mTc-HMPAO and compared with the results of a second study 3 weeks later when all symptoms of withdrawal had disappeared and when the patients had been free of medication for at least 1 week. Slice images were reconstructed parallel to the orbitomeatal plane, and tracer activity was analyzed in 8 regions of interest per hemisphere. During alcohol withdrawal a special pattern of cerebral blood flow distribution could be observed. Relative perfusion was elevated in both inferior temporal regions, whereas it was reduced in the superior temporal region of both hemispheres. The changes of cerebral blood flow distribution did not correlate with neuropsychological findings nor with the severity of withdrawal syndrome.

[Cerebral multisystem atrophy in a patient with depressive hallucinatory syndrome. A case report]. / Zerebrale Multisystematrophie bei einer Patientin mit depressiv-halluzinatorischem Syndrom. Ein Fallbericht.

In a female patient, aged 47 years at the beginning, the successive appearance of extrapyramidal signs preceded by depression, paranoid-hallucinatory psychosis, autonomic and cerebellar dysfunction was followed up over a period of 8 years. Autopsy revealed--in accordance with the clinical symptomatology--both olivo-ponto-cerebellar atrophy and a striatonigral degeneration. As a rule these changes are accompanied by dementia. The reported case is unusual in having first presented with severe depression and paranoid-hallucinatory symptoms.

Inappropriate vasopressin secretion in severe alcohol withdrawal.

Forty-one male alcoholics suffering from alcohol withdrawal syndrome were investigated to assess the relationship between vasopressin (ADH), water homeostasis and alcohol withdrawal. During 10 d, we found a significant decrease in serum vasopressin, from 3.08 +/- 0.61 to 1.71 +/- 0.22 pg/nl. There were no concomitant changes in osmolality, so that a general dysregulatory state of vasopressin secretion during alcohol withdrawal cannot be assumed. Only patients with delirium tremens (8/41) had higher vasopressin levels despite lowered serum osmolalities. These findings support the hypothesis of an inappropriate rebound secretion of vasopressin in severe alcohol withdrawal. Furthermore, they may contribute to the pathogenesis of focal alcoholic brain damage, because rapid and/or profound changes in osmolality are suspected to cause circumscribed cerebral demyelinization.

[Trauma-triggered migraine attacks. Review of the literature.]. / Traumatisch ausgelöste Migräneattacken (TAMA) Eine Literaturübersicht.

In children and young adults migraine attacks can be triggered by mild head injury. The literature on this syndrome was surveyed and 50 case reports found to meet the latest criteria of classification requiring at least two similar attacks for diagnosis of migraine (except for common migraine which was excluded from review). 33 subjects had at least one trauma-triggered attack and one identical or similar spontaneous attack, 17 cases at least two similar or identical trauma triggered attacks. An analysis of all cases showed the following features: The symptoms of migraine mostly start with a latency between one and thirty minutes after the injury and dissolve within one day. First attacks without mention of headache were mainly found in children younger than 8 years. Trauma-triggered migraine attacks are well documented for familial hemiplegic migraine, migraine attacks with hemispheric symptoms and attacks with disturbances of consciousness, while the view that posttraumatic transient cortical blindness and transient global amnesia are migraine attacks is insufficiently supported. A hereditary predisposition for a traumatic trigger mechanism seems to be present at least in familial hemiplegic migraine. Nosologic relations to syndromes of secondary neurological deterioration after mild head injury in childhood are discussed.