Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia.

Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily l-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here, we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID [PD-LID, n = 8)] as compared to non-dyskinetic PD patients receiving l-DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (i) decreased levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid in PD patients not receiving l-DOPA (ii) higher dopamine (DA) levels in PD-LID as compared to controls (iii) higher DA/l-DOPA and lower DOPAC/DA ratio's in PD-LID as compared to PD-L and (iv) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of l-DOPA-treated PD patients may help identify patients at risk of developing LID.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia.

[Diagnostics and treatment of functional dizziness in accordance with the new ICD-11 criteria].

Persistent postural-perceptual dizziness (PPPD) is a new diagnosis for functional chronic dizziness and included in the new International Classification of Diseases (ICD)-11. The new criteria are positive, specific and make it easier to identify and study functional chronic dizziness. PPPD is a condition triggered by vestibular-, neurological- or psychological conditions. This review examines the symptoms, pathophysiology and treatment of PPPD.

[Functional neurological symptoms and the positive diagnostic process].

Functional neurological symptoms are common in neurology and general medical practice. Functional neurological symptoms refer to neurological symptoms, which are not explained by a defined disease. The most common are functional weakness and non-epileptic seizures. Psychiatric models have dominated the classification, aetiology and treatment, limiting the neurologist's role to making the diagnosis by excluding disease and pronouncing the symptoms to be psychogenic. In this review, we outline the possibility of a positive diagnostic process, which can be the first step of treatment.

Sharing of a conserved haplotype suggests a susceptibility gene for multiple sclerosis at chromosome 17p11.

Multiple sclerosis (MS) is a chronic inflammatory disease resulting in demyelination in the central nervous system (CNS). Increasing evidence supports that genetic factors confer susceptibility to MS. One locus, the HLA complex (6p21), has been identified as important in MS, but no other loci have been clearly implicated, neither by a candidate gene approach, nor by a genomic screen strategy. Here, we studied a genetically isolated population in the northern-most part of Sweden, which demonstrates a high incidence of MS, using haplotype sharing analysis. Genealogical analysis demonstrated that 22 MS patients originate from a single common ancestral couple in the eighteenth century. Five affected individuals from four nuclear families were selected for an initial genomic screen with 390 microsatellite markers. Seven shared haplotypes in six different chromosomal regions were observed. After genotyping for these haplotypes with the same and additional markers in 15 MS patients and healthy relatives, some portion of a conserved haplotype spanning 10 cM at 17p11 was found to be shared by 12 of 15 affected individuals. The statistical analysis revealed a significant excess of transmission of alleles of three markers to affected individuals (P<0.05) by the transmission/disequilibrium test (TDT). An identical four-marker haplotype was shared by six of 15 patients (40%; P<0.01). Surprisingly, DR-typing revealed no significant sharing of the HLA region. In conclusion, our data suggests a novel susceptibility gene for MS in chromosome 17p11.

Illness beliefs and locus of control: a comparison of patients with pseudoseizures and epilepsy.

PURPOSE: The aim of this study was to examine the illness beliefs and locus of control of patients with recent onset pseudoseizures and to compare these with patients with recent onset epilepsy. METHODS: Twenty consecutive patients with pseudoseizures of recent onset (mean duration 5.4 months) were compared with 20 consecutive patients with recent onset epilepsy on their responses to (a) the Illness Behaviour Questionnaire (IBQ) and (b) a measure of locus of control, a dimension of the tendency to attribute events to internal or external factors. RESULTS: In comparison with patients with epilepsy, patients with recent onset pseudoseizures believed that psychological factors were less important than somatic ones were (P < .005) and had a greater tendency to deny nonhealth life stresses (P < .0001). No significant differences were detected in disease conviction or illness worry. Patients with pseudoseizures had a more external locus of control (P < .001), CONCLUSIONS: Patients with pseudoseizures are less likely than those with epilepsy to see psychological factors as relevant to their symptoms, more likely to deny that they have suffered from life stress and also to have a more external locus of control. The implications for treatment are discussed.

Recent onset pseudoseizures--clues to aetiology.

PURPOSE: To examine associations of potentially aetiological significance for the development of pseudoseizures by comparing patients with recent onset pseudoseizures with patients with recent onset epilepsy. METHODS: A prospective study of consecutive patients with recent onset pseudoseizures and epilepsy presenting to two Swedish hospitals. Demographic characteristics, somatic symptoms, depression severity, personality disorder, potential childhood aetiological factors and recent life events were elicited from clinical data and a research interview, which included a structured clinical interview for DSM-IV, a measure of perceived parental care and a life events inventory. RESULTS: Twenty patients with pseudoseizures of duration less than 12 months (mean 5.4 months) were compared with 20 patients with recent onset epilepsy. There was no statistically significant difference in the rate of current psychiatric disorder. Patients with recent onset pseudoseizures were however more likely to have a borderline personality disorder (P<0.05), and to recollect less parental warmth and more paternal rejection (P=0.0001) in childhood. They had no more life events in the 3 months prior to onset but did report more when the whole year before onset was assessed (P<0.001). CONCLUSIONS: Perceived childhood neglect, borderline personality, and an excess of life events over the preceding year is associated with pseudoseizures of recent onset more than with epilepsy. The study was limited by the small sample size making type two errors likely. However, by selecting both cases and controls with recent onset symptoms, the potential bias of differing illness durations and complicating factors of chronicity that have affected previous studies was avoided.

[Every fifth case of multiple sclerosis is familial]. / Hvert femte tilfælde af multipel sklerose anses for arveligt.

Up to 20% of all multiple sclerosis (MS) cases are familial. The concordance rates for monozygotic and dizygotic twins are 25-30% and 3-5% respectively. Certain isolated regions have a higher prevalence of MS. An estimated 30% of the disease heritability is accounted for, mostly by common risk alleles. Interpretation of risk alleles, gene-gene and gene-environment interactions is challenging, but all are believed to be important factors in the development of MS. Isolates and MS families are warranted for further research concerning these issues.

Woman with facial spasm induced exclusively by sound.

A woman is described in whom facial spasm occurs solely and predictably in the presence of certain noises. The symptoms resolve promptly as soon as the auditory stimulus stops.

Motor conversion symptoms and pseudoseizures: a comparison of clinical characteristics.

The authors prospectively studied consecutive neurological inpatients with either motor conversion symptoms or pseudoseizures of recent onset. Patients were administered a structured psychiatric diagnostic interview, a measure of perceived parental care, and a life events inventory. They found that patients with pseudoseizures (N=20, mean age=27 years): 1) were younger than patients with motor conversion symptoms (N=30, mean age=39 years), 2) were more likely to have a borderline personality disorder), 3) were more likely to have a lower perception of parental care and to report incest, and 4) reported more life events in the 12 months before symptom onset. These differences in their characteristics and associated factors raised the question of whether it is helpful to group patients with pseudoseizures and motor conversion symptoms in a single diagnostic category of conversion disorder. An alternative view, that gives primacy to the symptoms rather than a disorder, may enable more precise research questions to be posed.

Chronic pain disorder associated with psychogenic versus somatic factors: a comparative study.

Fifty-one consecutive non-depressed patients with chronic pain referred to a multidisciplinary pain clinic were assessed. In 32 patients, pain was judged to be associated with psychogenic factors only, while pain in 19 patients could be attributed solely to a general medical condition. The methods of investigation comprised visual analogue scales (VAS) and pain drawings, the Dysfunctional Attitude Scale (DAS), the Karolinska Scales of Personality (KSP), locus of control (LOC) and EMBU (for assessing perceived parental rearing practices). Mean age, gender distribution, analgesic consumption, pain duration, percentage of body area pain as well as body localization of pain were comparable in both groups. Patients with psychogenic pain reported higher levels of general bodily discomfort but less concentration difficulties and memory disturbances compared with the somatic pain patients. There were no significant intergroup differences on any of the LOC, DAS, KSP or EMBU items. LOC turned out to be extremely external, whereas DAS, KSP and EMBU scores were comparable to normal controls in earlier work. The paucity of differences between the two patient groups and the unremarkable personality structure of patients led to somewhat conflicting conclusions, and the results of the study pose one more piece of evidence for the futility of the dichotomous organic vs. psychogenic distinction of chronic pain disorders.