Adult onset idiopathic torsion dystonia is excluded from the DYT 1 region (9q34) in a Swedish family.

A gene (DYT1) for early onset idiopathic torsion dystonia was mapped to chromosome 9q34 in non-Jewish and Jewish families. The DYT1 gene region has been excluded in other families with adult onset and cervical or cranial onset idiopathic torsion dystonia from the United States, Great Britain, and France. The role of DYT1 in a Swedish family with adult onset idiopathic torsion dystonia in four generations was examined. The disease seems to be inherited in an autosomal dominant mode with reduced penetrance in this family. There were 10 affected family members, with a mean age of onset of 27 (range 18 to 50) years. The disease showed variable expression, with focal, multifocal, and generalised forms of dystonia in different family members. Genetic analysis excluded the chromosomal region containing the DYT1 locus as being responsible for dystonia in this family.

Hereditary myopathy with lactic acidosis, succinate dehydrogenase and aconitase deficiency in northern Sweden: a genealogical study.

A hereditary myopathy with lactic acidosis during physical exercise, low physical work capacity, and paroxysmal myoglobinuria (HML), called "Myopathy with deficiency of succinate dehydrogenase and aconitase" (McKusick 255125) has been described in 19 members of nine families who lived in two geographically separate areas in northern Sweden. By using the unique Swedish historical archives, including Catechetical Meeting Records from a number of northern Swedish parishes, it has been possible to trace ancestors of the nine families including all known 19 cases back in time to some key couples, who lived up to 300 years ago (that is seven to ten generations). No common single couple or common links between families in the past was found in these registers as a support for a single or several mutations that had developed far back in time. The mode of inheritance in this family is most likely autosomal recessive. This material will be used for the chromosomal localisation of the gene.

Substance P in CSF of patients with chronic pain syndromes.

Immunoreactive substance P was determined in lumbar CSF of 35 healthy volunteers and 60 patients with chronic pain syndromes of at least 6 months duration. No significant relationships were found between substance P levels and age, sex or body height. Substance P levels were lower in chronic pain patients, with either neurogenic (n = 23) or idiopathic pain (n = 37) syndromes, than in the healthy volunteers. Substance P levels were especially low in patients with neurogenic pain with lesions involving the extremities and in those with polyneuropathy, while patients with central pain or pain of the head or face had higher values. Substance P levels were related to depressive symptomatology as determined by means of visual analogue scales and to stable personality traits as determined by means of the Karolinska Scales of Personality (KSP). The most consistent (and inverse) relationship was found between substance P levels and the symptom 'inner tension' and between substance P levels and the personality trait 'psychic anxiety.'

Personality traits in patients with idiopathic pain disorder.

In the present study, patients with idiopathic pain syndromes have been compared to healthy volunteers, patients with neurogenic pain syndromes and depressed patients as concerns stable personality traits. The personality traits were assessed by means of the Karolinska Scales of Personality (KSP). Patients with idiopathic pain syndromes were found to have high scores on scales measuring Muscular tension, Social desirability, Psychasthenia and Socialization. They had also high scores on the Inhibition of aggression factor. They had low scores on Impulsivity, Monotony avoidance, Indirect aggression, Verbal aggression and Suspicion. As compared to depressed patients, the pain patients were much more controlled, with higher scores on Socialization and Social desirability scales and like depressed patients with a tendency to inhibit aggression. Thus, as compared to depressed patients, the pain patients had less open anxiety but the same degree of muscular tension.

Melatonin in serum and urine in patients with idiopathic pain syndromes.

In 16 healthy volunteers, 16 patients with neurogenic pain syndromes, 37 patients with idiopathic pain syndromes, and 30 depressed patients, melatonin in serum was determined at 2 a.m. when the peak concentration was expected. In a somewhat larger series comprising 53 healthy volunteers, 14 patients with neurogenic pain syndromes, and 35 patients with idiopathic pain syndromes, melatonin was measured in urine collected during the night in a standardized manner. Chronic pain patients (with neurogenic or idiopathic pain disorders) and depressed patients had significantly lower melatonin in serum at 2 a.m. than healthy volunteers. Chronic pain patients also had significantly lower melatonin in urine than healthy volunteers, even when age, sex, and body weight were taken into account. The low melatonin concentrations were related to increased depressive symptomatology, especially sadness, bodily discomfort, inner tension, concentration difficulties, and pain. As low concentrations of melatonin in serum and urine also are found in patients with depressive disorders, the results are in line with the suggestion that the chronic idiopathic pain syndrome may be a variant of depressive disease, or the two syndromes may share a common pathogenic mechanism.

5-HIAA and HVA in CSF in patients with idiopathic pain disorders.

Patients with idiopathic pain syndromes were compared with healthy volunteers and with patients suffering from chronic pain syndromes of neurogenic origin, with respect to the concentrations of the metabolites 5-hydroxy-indole-acetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF). Patients with idiopathic pain syndromes were subdivided according to the presence or absence of somatic lesions. It was found that these groups did not differ in concentrations of 5-HIAA or HVA, at least not when values were corrected for age, sex, and body height. Patients with idiopathic pain syndromes were found to have low concentrations of 5-HIAA, but not of HVA, in CSF. These differences were also obvious when the values were corrected for age, sex, and body height. As low concentrations of 5-HIAA in CSF have previously been demonstrated in patients with depressive disorders, our results support the suggestion by Blumer and Heilbronn (1982) that the idiopathic pain syndrome is a variant of depressive disease. At least the two syndromes share a common pathogenetic mechanism--a disturbance in serotonergic turnover.

Platelet MAO in patients with idiopathic pain disorders.

Patients with idiopathic pain syndromes have been compared to healthy volunteers and patients with neurogenic pain syndromes as concerns the activity of the enzyme monoamine oxidase (MAO) in thrombocytes. In both patients with idiopathic pain syndromes and in patients with neurogenic pain syndromes an increased frequency of patients with low platelet MAO activity was found. As low platelet MAO activity has been suggested to reflect low central serotoninergic activity the results are in line with findings of reduced concentrations of the serotonin metabolite 5-HIAA in CSF in patients with idiopathic pain syndromes. The results would also give some support for the suggestion that idiopathic pain syndromes might be a variant of depressive disease.

Monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5 HIAA) and homovanillic acid (HVA) in motor neuron disease.

Thrombocyte monoamine oxidase (MAO) activity and concentrations of 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid (CSF) were studied in patients with motor neuron disease (MND) and healthy controls. The MAO activity in MND (n = 32) did not differ from age and sex-matched controls (n = 27) or from healthy relatives (n = 9) and no difference was found between advanced and mild cases. In an attempt to explain divergent results from other studies, the effect of storage time on analysis of platelet concentration was studied in three healthy subjects and in three patients with MND. No difference was observed between the groups. No differences were found between the MND group (n = 28) and healthy controls (n = 18) with regard to CSF levels of 5-HIAA and HVA, except for an increase of 5-HIAA among males with MND. The results of this study do not confirm earlier studies that have reported extensive changes in the variables analyzed in patients with MND.

Discrimination of idiopathic pain syndromes from neurogenic pain syndromes and healthy volunteers by means of clinical rating, personality traits, monoamine metabolites in CSF, serum cortisol, platelet MAO and urinary melatonin.

The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating chronic pain patients from healthy subjects, and patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.

Long-term high frequency transcutaneous electrical nerve stimulation (hi-TNS) in chronic pain. Clinical response and effects on CSF-endorphins, monoamine metabolites, substance P-like immunoreactivity (SPLI) and pain measures.

Eighteen patients with chronic pain syndromes of organic origin were treated by means of high frequency transcutaneous nerve stimulation (hi-TNS). The CSF levels of receptorassayable Fraction I and II endorphins, substance P-like immunoreactivity (SPLI), and the monoamine metabolites 5-HIAA, HVA and MOPEG were measured before and after one week of daily treatment. Furthermore, the effects on experimental pain measures were determined. The therapeutic effect was evaluated after 30 days and 3 months of treatment. Patients with low initial concentrations of endorphins in CSF, lower than those observed in healthy volunteers, tended to have the best response to hi-TNS. There were significant increases in Fraction I endorphins and SPLI in CSF, most pronounced in the patients who responded. There were no significant changes in 5-HIAA, HVA or MOPEG in CSF. However, in early responders, the serotonin metabolite 5-HIAA tended to decrease as contrasted to an increase in non-responders. The difference between the groups was statistically significant. Confirming our earlier studies, the therapy induced changes in pain measures showed a significant, positive correlation with increasing Fraction I endorphins in CSF. Our results suggest that hi-TNS induces central changes in the endorphinergic, serotonergic and possibly substance-P-ergic systems.

Epidemiology of motor neuron disease in northern Sweden.

All cases of motor neuron disease (MND), encompassing amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP) and progressive spinal muscular atrophy (PSMA), in northern Sweden, diagnosed between 1969-1980 have been analysed. 128 cases were found, corresponding to an average annual incidence rate of 1.67 per 100,000. The prevalence on December 31, 1980 was 4.8 per 100,000. Age-specific incidence rates were higher in the high age groups with a maximum at 60-64 years for males, at 70-74 years for females and at 65-69 years for the sexes combined. The median age at onset was 61 years. Clustering was not found in mining districts and overrepresentation of miners and stone treaters was not observed. Minor differences in incidence rates, as measured by the standardized morbidity ratio, SMR, were found between the inland, coastal and mountain areas. The median survival time after onset of disease was 32 months for ALS, 30 months for PBP and 70 months for PSMA. The combined survival rate for all MND cases was 28% after 5 years and 15% after 10 years. The male to female ratio was 1.1:1, and 4.7% were familial cases.

Brain monoamine abnormalities in the two types of Creutzfeldt-Jakob disease.

Analysis of monoamine concentrations in brain tissue was carried out on the two types of Creutzfeldt-Jakob disease (CJD). The results showed decreased levels of catecholamines compared to control cases in a number of areas, and the reductions were most pronounced for dopamine. In general, the case classified as the amyotrophic form of CJD showed a greater degree of a monoamine loss than the case with spongiform encephalopathy, which is the typical transmissible form of CJD. These findings support the scarce available data indicating disturbances in the catecholaminergic systems in these types of brain diseases, and may have therapeutic implications.

Circannual variation in concentrations of endorphins in cerebrospinal fluid.

In a series of 90 patients with chronic pain syndromes of psychogenic and organic etiology, the concentrations of fraction I endorphins in cerebrospinal fluid were investigated. A significant circannual variation in the concentrations of endorphins was found, with the highest concentrations in January-February and the lowest concentrations in July-August. There was no corresponding seasonal variation with regard to age, sex, bodylength, possible etiology of the pain syndrome self-rated pain levels, or experimental pain measures. Circannual difference in the intensity of symptoms in chronic pain syndromes and in affective disorders have been described in the literature. The present results suggest an association between these observations, giving further support for functional importance of endorphins in chronic pain.

Personality factors related to the outcome of treatment with transcutaneous nerve stimulation.

Personality factors are known to influence the augmenting/reducing tendency in evoked potentials and also the results obtained from pain-relieving methods in chronic pain conditions. In this study 30 chronic pain patients treated with high frequency transcutaneous electrical nerve stimulation were evaluated by means of personality inventories and visual evoked potentials (VEP). The results indicate that the group for whom the treatment had a positive outcome had an augmenting tendency in VEP and also significantly differed as regards certain factors in the EPI (high values in the L scale) and the CMPS (high values in factors I, II, IX, X and index I, V) personality inventories.

Predictors for the outcome of treatment with high frequency transcutaneous electrical nerve stimulation in patients with chronic pain.

Seventy-two patients suffering from chronic pain were treated with high frequency transcutaneous electrical nerve stimulation (hi-TNS). Significant predictors for a positive result were pains of neurogenic origin and pains located mainly in the extremities. CSF endorphin levels were determined for 22 patients with organic pain and the group with positive results from the treatment had somewhat (but not significantly) lower levels of fraction I endorphins. Age, sex or reported severity of pain had no predictive value.

Personality traits in chronic pain patients related to endorphin levels in cerebrospinal fluid.

Interindividual differences in endorphin levels may relate to widespread changes in adaptive processes, and endorphin levels may thus be related to personality traits. In 40 patients with chronic pain syndromes of both psychogenic and organic origin, endorphin levels in cerebrospinal fluid (CSF) were determined, and the patients completed Eysenck's Personality Inventory (EPI) and the Cesarek Marke Personality Scheme. Twenty-seven of the patients also completed the Zuckerman Sensation Seeking Scale (SSS). As a comparison group 30 healthy volunteers completed the personality inventories. The chronic pain patients were characterized by guilt feelings, need for order, low need for autonomy, and low tendency toward sensation seeking. Low levels of endorphins in CSF were found in patients with high scores on all the subscales in the SSS and low scores on the neuroticism subscale in the EPI.

Endorphins in CSF of chronic pain patients, in relation to augmenting-reducing response in visual averaged evoked response.

In 45 consecutive patients with chronic pain, visual averaged evoked responses (VAER) and the levels of fraction 1 endorphins in CSF were investigated. Patients with an augmenter response in VAER, i.e. the maximum amplitude increases when stimulus intensity is increased, were found to have significantly lower levels of fraction 1 endorphins than patients with a reducer response, i.e. the maximum amplitude in VAER decreases when stimulus intensity is increased. The results indicate that the endorphins function as endogenous antinociceptive factors.