[Hypersalivation - Update of the S2k guideline (AWMF) in short form]. / Hypersalivation ­ Aktualisierung der S2k-Leitlinie (AWMF) in gekürzter Darstellung.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation.Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes in order to activate compensation mechanisms as long compliances is given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the E. U. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Here, a phase III trial is completed for Incobotulinum toxin A and, in the U. S., is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3 D techniques to minimize tissue damage. Therapy effects and symptom severity has to be followed, especially in cases with underlying neurodegenerative disease.

Hypersalivation: update of the German S2k guideline (AWMF) in short form.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes to activate compensation mechanisms as long compliances are given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the EU. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long-lasting saliva reduction. Here, a phase III trial is completed for incobotulinum toxin A and, in the US, is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3D techniques to minimize tissue damage. Therapy effects and symptom severity have to be followed, especially in cases with underlying neurodegenerative disease.

Personality profiles are different in musician's dystonia and other isolated focal dystonias.

Psychological abnormalities have been reported in patients with musician's dystonia. To further differentiate these abnormalities, we evaluated personality traits in musician's dystonia and compared them to those in other isolated focal dystonias. Therefore patients with musician's dystonia (n = 101) and other isolated focal dystonias (n = 85) underwent the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). Women with musician's dystonia had higher NEO-FFI neuroticism scores, and men significantly higher openness scores compared to women and men with other isolated focal dystonias, respectively. There were negative correlations in men with musician's dystonia between duration of dystonia and the NEO-FFI openness and extraversion scores and between age and extraversion scores. Women with other isolated focal dystonias showed correlations between age and agreeableness and conscientiousness scores. Patients with musician's dystonia are characterized by a specific personality profile with increased neuroticism and openness compared to other isolated focal dystonias. Whether this profile can be traced back to specific underlying disease mechanisms should be further investigated.

Associations of specific psychiatric disorders with isolated focal dystonia, and monogenic and idiopathic Parkinson's disease.

Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of 2.6 [confidence interval (CI) 1.7-4.0] for general axis I disorders in IFD, an OR of 2.5 (CI 1.4-4.7) in monogenic PD, and an OR of 1.4 (CI 0.8-2.6) in idiopathic PD. More specifically, the monogenic PD group showed the highest ORs for affective disorders including depression (OR = 4.9), bipolar disorder (OR = 17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in the PD groups but not in IFD. Our findings underline the notion that psychiatric disorders are part of the phenotypic spectrum of movement disorders. Moreover, they suggest that IFD, monogenic PD, and idiopathic PD are associated with specific psychiatric disorders indicating disturbances in a different neural circuitry for sensorimotor control.

Altered velocity processing in schizophrenia during pursuit eye tracking.

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%-80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity.

Risk for antipsychotic-induced extrapyramidal symptoms: influence of family history and genetic susceptibility.

OBJECTIVES: This study aims to further evaluate the impact of family history of primary movement disorders (FHpMD) and a candidate genetic variant on risk of antipsychotic-induced extrapyramidal symptoms (EPS). METHODS: We examined 156 (76 men) inpatients receiving antipsychotics for EPS and FHpMD stratified by patient characteristics. The genetic analysis included genotyping of a multiallelic dinucleotide polymorphism in the ATP1A3 gene. RESULTS: EPS lifetime prevalence was 69% and more frequent in the presence of FHpMD (p = 0.052), particularly in patients younger than 60 years (p = 0.012) and with acute dystonic reactions. The ATP1A3 polymorphism showed an allele length-dependent association with parkinsonism (p=0.019 uncorrected, p=0.057 corrected) exclusively. Carriers of the shortest allele had a 7.7-fold increased risk for parkinsonism. CONCLUSIONS: The association of FHpMD and EPS may be linked to the EPS subtype and age of the patient. A common ATP1A3 genomic variation may represent a susceptibility factor for the risk for antipsychotic-induced parkinsonism in an allele-dependent manner.

Restless legs syndrome as a possible predictor for psychiatric disorders in parents of children with ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a common disorder with estimated prevalence of 5% in children and 3.4% in adults. Psychiatric disorders are a frequent concomitant feature. Restless legs syndrome (RLS) may mimic the symptoms of ADHD. The aim of the study is to evaluate whether the presence of RLS predicts occurrence of psychiatric disorders in parents of children with ADHD. Thirty-seven parents of 26 children with ADHD were examined for RLS and for lifetime prevalence rates of psychiatric disorders and personality disorders based on the Structured Clinical Interview for DSM-IV Diagnoses (SCID). Prevalence rates in parents were 29.7% for RLS, 67.6% for Axis I and 40.5% for Axis II disorders. Mothers revealed higher rates for depression, anxiety disorders and ADHD than fathers, whereas personality disorders occurred at higher rates in fathers. The presence of RLS predicted a diagnosis of ADHD (odds ratio (OR) 21.9), agoraphobia (OR = 20.4) and any anxiety disorder (OR = 8.5). Although limited by the small sample size, we found evidence for increased rates of cluster B personality disorders (OR = 59.3) in parents with RLS. All parents of the latter group (100%) reported a positive family history of psychiatric disorders which was not the case in parents without RLS (69.2%) excluding the index children with ADHD. RLS seems to indicate increased vulnerability for psychiatric disorders, i.e., ADHD and anxiety disorders, in a subgroup of parents from ADHD children. Synaptic dysfunction affecting dopaminergic transmission among other transmitter systems may be a common final pathway related to the phenotypic spectrum of ADHD.

Nonmotor symptoms in genetic Parkinson disease.

OBJECTIVES: To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD. DATA SOURCES: A MEDLINE search using Parkinson and known PD genes focused on the presence of depression, anxiety, hallucinations, and dementia was performed. Original data from 82 outpatients with idiopathic (n = 55) and genetic (n = 27) PD were obtained. STUDY SELECTION: All studies including information on NMS and patients with genetic PD. DATA EXTRACTION: Study methods and clinical and genetic information were summarized. DATA SYNTHESIS: The literature search yielded 1855 citations; 305 included genetic information on PD patients, of which 119 also contained information on any type of NMS (990 cases). Availability of information varied by gene and type of NMS; studies differed by recruitment and examination method. Literature search and original data showed high frequencies of the following NMS: depression, 8% to 37% (literature) and 33% to 40% (our data); anxiety, 7% to 37% (literature) and 10% to 22% (our data); hallucinations, 3% to 23% (literature) and 23% to 29% (our data); and dementia, 5% to 26% (literature), absent in our own data. CONCLUSIONS: Data on NMS in genetic PD are limited. Specific data needs include a systematic approach to NMS assessment reporting permitting comparability of studies. Overall, the frequency of NMS in genetic PD does not appear to be higher and may even be lower than in idiopathic PD. Nonmotor symptoms have a high impact on the patients' quality of life and caregiver burden and should be considered important and often treatable concomitant features of genetic PD.

Botulinum toxin B as an effective and safe treatment for neuroleptic-induced sialorrhea.

RATIONALE: Severe sialorrhea is a common, potentially stigmatizing and disabling side-effect of neuroleptic drugs such as clozapine. Sialorrhea also occurs in neurological disorders such as Parkinson's disease (PD). For neurological diseases, several studies have demonstrated botulinum toxin type B to be a safe and effective treatment. OBJECTIVES: To evaluate the treatment effects, tolerance, and duration of treatment-induced effects of botulinum toxin type B (Neurobloc) in the context of neuroleptic-induced sialorrhea (group 1) or PD-associated drooling (group 2) in a double-blind, placebo-controlled trial. METHODS: Nine patients (four from group 1; five from group 2) with severe sialorrhea received injections into the salivary glands with either botulinum toxin type B or placebo and were followed over 16 weeks. RESULTS: We found large effect sizes for improvement of sialorrhea in patients treated with botulinum toxin type B, whereas the improvement of sialorrhea in those receiving placebo was only small. No patient reported any side effects. Reduction of sialorrhea lasted for 8 to 16 weeks after a single injection. CONCLUSIONS: Like for PD, botulinum toxin type B represents an effective and safe treatment for neuroleptic-induced sialorrhea with a treatment effect of 8 to 16 weeks.

Structural changes associated with progression of motor deficits in spinocerebellar ataxia 17.

Spinocerebellar ataxia (SCA17) is a rare genetic disorder characterized by a variety of neuropsychiatric symptoms. Recently, using magnetic resonance imaging (MRI) voxel-based morphometry (VBM), several specific functional-structural correlations comprising differential degeneration related to motor and psychiatric symptoms were reported in patients with SCA17. To investigate gray matter volume (GMV) changes over time and its association to clinical neuropsychiatric symptomatology, nine SCA17 mutation carriers and nine matched healthy individuals underwent a detailed neuropsychiatric clinical examination and a high-resolution T1-weighted volume MRI scan, both at baseline and follow-up after 18 months. Follow-up images revealed a progressive GMV reduction in specific degeneration patterns. In contrast to healthy controls, SCA17 patients showed a greater atrophy not only in cerebellar regions but also in cortical structures such as the limbic system (parahippocampus, cingulate) and parietal precuneus. Clinically, progression of motor symptoms was more pronounced than that of psychiatric symptoms. Correlation with the clinical motor scores revealed a progressive reduction of GMV in cerebellar and cerebral motor networks, whereas correlation with psychiatric scores displayed a more widespread GMV impairment in frontal, limbic, parietal, and also cerebellar structures. Interestingly, changes in global functioning were correlated with bilateral atrophy within the para-/hippocampus. While there was a good temporal association between worsening of motor symptoms and progression in cerebral and cortical neurodegeneration, the progression in psychiatric related neurodegeneration seemed to be more widespread and complex, showing progressive atrophy that preceded the further development of clinical psychiatric symptoms.

Limbic and frontal cortical degeneration is associated with psychiatric symptoms in PINK1 mutation carriers.

BACKGROUND: Mutations in the PINK1 gene can cause Parkinson's disease and are frequently associated with psychiatric symptoms that might even precede motor signs. METHODS: To determine whether specific gray matter degeneration of limbic and frontal structures might be liable to different psychiatric symptoms in PINK1 mutation carriers, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 14 PINK1 mutation carriers from a large German family and 14 age- and gender-matched healthy control subjects. RESULTS: Psychiatric diagnoses in PINK1 mutation carriers comprised major depression without psychotic symptoms and schizophrenia-spectrum, panic, adjustment, and obsessive-compulsive personality disorders. As hypothesized, the categorical comparison between all PINK1 mutation carriers and control subjects demonstrated atrophy of limbic structures, especially the hippocampus and parahippocampus. More specifically, multiple regression analysis considering all psychiatric subscores simultaneously displayed different frontal (prefrontal, dorsolateral, and premotor cortex) and limbic (parahippocampus and cingulate) degeneration patterns. The duration of the psychiatric disease was also correlated with the extent of limbic and frontal gray matter volume decrease. CONCLUSIONS: Our results support the hypothesis that limbic and frontal gray matter alterations could explain various psychiatric symptoms observed in PINK1 mutation carriers. Factors determining individual susceptibility to degeneration of certain brain areas remain to be elucidated in future studies.

Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations.

OBJECTIVE: To investigate a possible association of mutations in the PTEN-induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism. METHOD: 20 members of a family (4 homozygous, 11 heterozygous and 5 non-mutation carriers) were investigated for the presence of psychiatric disorders using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); information on three additional heterozygous mutation carriers was obtained according to the family history research diagnostic criteria. RESULTS: We found predominantly affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation carriers and in 1 (20%) of the 5 mutation-negative cases. CONCLUSIONS: First, affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations. Second, patients with familial movement disorders associated with psychiatric conditions may serve as a valuable study population to explore (genetic) causes of neuropsychiatric disease.

Clinical spectrum of homozygous and heterozygous PINK1 mutations in a large German family with Parkinson disease: role of a single hit?

BACKGROUND: Although homozygous mutations in the PTEN-induced putative kinase 1 (PINK1) gene have been unequivocally associated with early-onset Parkinson disease (PD), the role of single heterozygous PINK1 mutations is less clear. OBJECTIVE: To investigate the role of homozygous and heterozygous PINK1 mutations in a large German pedigree (family W). DESIGN: Mutation analysis of PINK1 and results of standardized neurological and motor examination by 3 independent movement disorder specialists, including blinded video rating. SETTINGS: University of Lübeck. PARTICIPANTS: Twenty family members. MAIN OUTCOME MEASURES: The PINK1 genotype and PD status of all family members. RESULTS: The index patient of family W carried a homozygous nonsense mutation (c.1366C>T; p.Q456X) and presented with a phenotype closely resembling idiopathic PD but with an onset at 39 years of age. The family included a total of 4 affected homozygous members (age, 60-71 years; age at onset, 39-61 years), 6 members with slight or mild signs of PD (affected) and a heterozygous mutation (age, 31-49 years), and 5 unaffected heterozygous mutation carriers (age, 34-44 years). Although none of the heterozygous affected family members was aware of their signs (asymptomatic), the clinical findings were unequivocal and predominantly or exclusively present on their dominant right-hand side, eg, unilaterally reduced or absent arm swing and unilateral rigidity. The heterozygous members were all considerably younger than the affected homozygous mutation carriers. CONCLUSIONS: Heterozygous PINK1 mutations may predispose to PD, as was previously suggested by the presence of dopamine hypometabolism in asymptomatic mutation carriers. Long-term follow-up of our large family W provides an excellent opportunity to further evaluate the role of single heterozygous PINK1 mutations later in life, which will have major implications on genetic counseling.