[The new Parkinson's disease pain classification system (PD-PCS)]. / Die neue Parkinson-Schmerzklassifikation (PSK).

BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.

The spatial distribution of perseverations in neglect patients during a nonverbal fluency task depends on the integrity of the right putamen.

Deficient inhibitory control leading to perseverative behaviour is often observed in neglect patients. Previous studies investigating the relationship between response inhibition and visual attention have reported contradictory results: some studies found a linear relationship between neglect severity and perseverative behaviour whereas others could not replicate this result. The aim of the present study was to shed further light on the interplay between visual attention and response inhibition in neglect, and to investigate the neural underpinnings of this interplay. We propose the use of the Five-Point Test, a test commonly used to asses nonverbal fluency, as a novel approach in the context of neglect. In the Five-Point Test, participants are required to generate as many different designs as possible, by connecting dots within forty rectangles. We hypothesised that, because of its clear definition of perseverative errors, the Five-Point Test would accurately assess both visual attention as well as perseverative behaviour. We assessed 46 neglect patients with right-hemispheric stroke, and performed voxel-based lesion-symptom mapping (VLSM) to identify neural substrates of perseverative behaviour as well as the spatial distribution of perseverations. Our results showed that the Five-Point Test can reliably measure neglect and perseverative behaviour. We did not find any significant relationship between neglect severity and the frequency of perseverations. However, within the subgroup of neglect patients who displayed perseverative behaviour, the spatial distribution of perseverations significantly depended on the integrity of the right putamen. We discuss the putative role of the putamen as a potential subcortical hub to modulate the complex integration between visual attention and response inhibition processes.

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia.

OBJECTIVE: Formal thought disorder (FTD) is a core symptom in schizophrenia. Here, we focus on resting state cerebral blood flow (rCBF) linked to dimensions of FTD. METHODS: We included 47 schizophrenia spectrum patients and 30 age- and gender-matched healthy controls. We assessed FTD with the assessment of thought, language, and communication (TLC) and imaging on a 3T MRI scanner. Within patients, we tested the association of FTD dimensions and in a subgroup (n = 27) the association of functional outcome after 6 months with whole brain rCBF. RESULTS: Negative FTD was most prominently associated with perfusion within the superior temporal gyrus, while positive FTD was associated with perfusion within the supplementary motor area, and inferior frontal gyrus. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. CONCLUSIONS: Distinguishable associations of rCBF with FTD dimensions point to distinct underlying pathophysiology. The location of aberrant perfusion patterns suggests that negative FTD might reflect defective access to semantic memory while positive FTD likely reflects defective suppression of irrelevant information during increased speech production. Finally, the neural correlates of thought block were also predictive of poor functional outcome. Thus, functional outcome and distinct FTD dimensions may share some pathophysiology.

[Networks involved in motor cognition : Physiology and pathophysiology of apraxia]. / Netzwerke für motorische Kognition : Physiologie und Pathophysiologie der Apraxie.

Apraxia is an umbrella term for different disorders of higher motor abilities that are not explained by elementary sensorimotor deficits (e. g. paresis or ataxia). Characteristic features of apraxia that are easy to recognize in clinical practice are difficulties in pantomimed or actual use of tools as well as in imitation of meaningless gestures. Apraxia is bilateral, explaining the cognitive motor disorders and occurs frequently (but not exclusively) after left hemispheric lesions, as well as in neurodegenerative diseases, such as corticobasal syndrome and Alzheimer's disease. Apraxic deficits can seriously impair activities of daily living, which is why the appropriate diagnosis is of great relevance. At the functional anatomical level, different cognitive motor skills rely on at least partly different brain networks, namely, a ventral processing pathway for semantic components, such as tool-action associations, a ventro-dorsal pathway for sensorimotor representations of learnt motor acts, as well as a dorso-dorsal pathway for on-line motor control and, probably, imitation of meaningless gestures. While these networks partially overlap with language-relevant regions, more clear cut dissociations are found between apraxia deficits and disorders of spatial attention. In addition to behavioral interventions, noninvasive neuromodulation approaches, as well as human-computer interface assistance systems are a growing focus of interest for the treatment of apraxia.

Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study.

BACKGROUND AND PURPOSE: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant. METHODS: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale. RESULTS: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors. CONCLUSIONS: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills.

Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST).

BACKGROUND: Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. METHODS: The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. RESULTS: The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. CONCLUSION: The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke.

Short and valid assessment of apraxia in Parkinson's disease.

BACKGROUND: Valid assessment of apraxia in usually non-apraxic Parkinson's disease helps to delineate atypical parkinsonism frequently associated with apraxia. Furthermore, in a subgroup of late Parkinson's disease apraxia, typically the ideomotor subtype, may gradually superimpose onto parkinsonian motor symptoms contributing to defective manual skill. Here we evaluate the utility of a brief, standardized test, the apraxia screen of TULIA (AST). METHODS: Seventy five Parkinson's disease patients were tested with the AST. Parkinsonian motor deficits were measured using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III and difficulties in activities of daily living (ADL) by modified MDS-UPDRS part II (eating, dressing, personal hygiene, and writing). RESULTS: No association was found between the AST and MDS-UPDRS part III, indicating that AST discriminates well (discriminative validity) between apraxia and parkinsonism. Furthermore, AST was associated with ADL and Hoehn & Yahr stage (convergent validity). CONCLUSIONS: AST is a short and valid test to rule out or detect apraxia in Parkinson's disease.

Impaired finger dexterity in Parkinson's disease is associated with praxis function.

A controversial concept suggests that impaired finger dexterity in Parkinson's disease may be related to limb kinetic apraxia that is not explained by elemental motor deficits such as bradykinesia. To explore the nature of dexterous difficulties, the aim of the present study was to assess the relationship of finger dexterity with ideomotor praxis function and parkinsonian symptoms. Twenty-five patients with Parkinson's disease participated in the study. Their left and right arms were tested independently. Testing was done in an OFF and ON state as defined by a modified version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Finger dexterity was assessed by a coin rotation (CR) task and ideomotor praxis using a novel test of upper limb apraxia (TULIA), in which the patients were requested to imitate and pantomime 48 meaningless, as well as communicative and tool-related gestures. Coin rotation significantly correlated with TULIA irrespective of the motor state and arm involved, but not with the MDS-UPDRS. This association was significantly influenced by Hoehn and Yahr stage. The strong association of finger dexterity with praxis function but not the parkinsonian symptoms indicates that impaired finger dexterity in Parkinson's disease may be indeed apraxic in nature, yet, predominantly in advanced stages of the disease when cortical pathology is expected to develop. The findings are discussed within a cognitive-motor model of praxis function.

A new bedside test of gestures in stroke: the apraxia screen of TULIA (AST).

BACKGROUND: Apraxia in patients with stroke may be overlooked, as clumsiness and deficient gestural communication are often attributed to frequently coexisting sensorimotor deficits and aphasia. Early and reliable detection of apraxia by a bedside test is relevant for functional outcome in patients with stroke. The present study was aimed at constructing a new bedside screening test for apraxia, called the Apraxia Screen of TULIA (AST), based on the comprehensive standardised Test for Upper-Limb Apraxia (TULIA). METHODS: First, an item-reduction analysis of the TULIA (48 gestures) was performed, based on the methods of classical test theory and on a larger sample of patients with stroke (n=133) and matched healthy controls (n=50). Stepwise elimination of items resulted in a set of 12 items, demonstrating high internal consistency (Cronbach alpha=0.92). The six-point scoring method of the TULIA was dichotomised to the score levels pass and fail. In the second part of this study the validity of the AST was assessed prospectively in a new cohort of patients with stroke (n=31) by using the Pearson correlation analysis and binary classification display with the TULIA. RESULTS AND DISCUSSION: Validation of the 12-item AST with the TULIA showed a remarkable diagnostic reliability with high specificity, sensitivity and positive predictive value, for the presence and severity of apraxia. The AST is shown to be a reliable and valid bedside test in patients with stroke, allowing a straightforward assessment of apraxia within a few minutes.

Comprehensive assessment of gesture production: a new test of upper limb apraxia (TULIA).

BACKGROUND: Only few standardized apraxia scales are available and they do not cover all domains and semantic features of gesture production. Therefore, the objective of the present study was to evaluate the reliability and validity of a newly developed test of upper limb apraxia (TULIA), which is comprehensive and still short to administer. METHODS: The TULIA consists of 48 items including imitation and pantomime domain of non-symbolic (meaningless), intransitive (communicative) and transitive (tool related) gestures corresponding to 6 subtests. A 6-point scoring method (0-5) was used (score range 0-240). Performance was assessed by blinded raters based on videos in 133 stroke patients, 84 with left hemisphere damage (LHD) and 49 with right hemisphere damage (RHD), as well as 50 healthy subjects (HS). RESULTS: The clinimetric findings demonstrated mostly good to excellent internal consistency, inter- and intra-rater (test-retest) reliability, both at the level of the six subtests and at individual item level. Criterion validity was evaluated by confirming hypotheses based on the literature. Construct validity was demonstrated by a high correlation (r = 0.82) with the De Renzi-test. CONCLUSION: These results show that the TULIA is both a reliable and valid test to systematically assess gesture production. The test can be easily applied and is therefore useful for both research purposes and clinical practice.

Gesture subtype-dependent left lateralization of praxis planning: an event-related fMRI study.

Ideomotor apraxia is a disorder mainly of praxis planning, and the deficit is typically more evident in pantomiming transitive (tool related) than intransitive (communicative) gestures. The goal of the present study was to assess differential hemispheric lateralization of praxis production using event-related functional magnetic resonance imaging. Voxel-based analysis demonstrated significant activations in posterior parietal cortex (PPC) and premotor cortex (PMC) association areas, which were predominantly left hemispheric, regardless of whether planning occurred for right or left hand transitive or intransitive pantomimes. Furthermore, region of interest-based calculation of mean laterality index (LI) revealed a significantly stronger left lateralization in PPC/PMC clusters for planning intransitive (LI = -0.49 + 0.10, mean + standard deviation [SD]) than transitive gestures (-0.37 + 0.08, P = 0.02, paired t-tests) irrespective of the hand involved. This differential left lateralization for planning remained significant in PMC (LI = -0.47 + 0.14 and -0.36 + 0.13, mean + SD, P = 0.04), but not in PPC (-0.56 + 0.11 and -0.45 + 0.12, P = 0.11), when both regions were analyzed separately. In conclusion, the findings point to a left-hemispheric specialization for praxis planning, being more pronounced for intransitive gestures in PMC, possibly due to their communicative nature.

Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study.

Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.

Hierarchical versus parallel processing in tactile object recognition: a behavioural-neuroanatomical study of aperceptive tactile agnosia.

The organization of the normal perceptual processing subserving tactile object recognition is poorly understood. While perceptual deficits associated with cases of tactile agnosia may pinpoint sites of critical interference with normal tactile information processing, the precise character of such deficits remains unclear. The aim of the present study was to explore the behavioural and neuroanatomical correlates of perceptual disturbances in two cases of unilateral aperceptive tactile agnosia. Perception of microgeometrical and macrogeometrical features was tested using an alternative forced choice paradigm. While both patients were impaired in the assessment of microgeometrical properties of objects (i.e. detecting subtle differences in grating profiles), one patient showed an additional deficit in the perception of macrogeometrical properties of objects (i.e. detecting differences in length of cuboids). The pattern of perceptual deficits for both patients suggested a severely compromised (if not totally lost) ability to recognize everyday objects. Perceptual performance improved when the patients had complementary tactile information (i.e. for intramodal comparison), despite a persistent inability to explicitly name the objects. That is, the patients were able to recognize objects, but only implicitly. Improved perceptual performance was also observed when complementary visual information was available (i.e. transmodal information transfer). In this case, the perceptual improvement was accompanied by a corresponding improvement in explicit object recognition. High resolution MRIs identified lesions in the postcentral gyrus in both patients, and additionally in the secondary somatosensory area (SII) and the posterior parietal cortex in the more severely affected patient. The results demonstrate that the underlying failure in tactile agnosia is mainly impaired perception of microgeometrical properties of objects due to a lesion of primary sensory cortex. The related neuroanatomical findings suggest a degradation of serial information processing within postcentral gyrus. In one case tactile agnosia was almost complete due to additionally impaired perception of macrogeometrical properties of objects, which correlated with the extension of lesion to the posterior parietal cortex. Importantly, the findings indicate traces of two distributed networks for tactile information processing and the associated parallel processing of complementary micro- and macrogeometrical information within postcentral gyrus and posterior parietal lobe.

Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men.

Anxiolytic and sedative effects of neuropeptide Y (NPY) are thought to involve inhibition of corticotropin-releasing hormone (CRH). Enhanced secretion of CRH plays a critical role in the pathophysiology of major depression, characterized by sleep disturbances, anxiety and loss of appetite. We examined for the first time in young men effects of intravenous injections of NPY (4x50 or 100 microg, n = 9 and 11, respectively, at 22.00, 23.00, 24. 00 and 01.00 compared to saline) on the sleep electroencephalogram (EEG; recorded from 23.00 to 07.00) and nocturnal secretion of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (GH), prolactin and leptin. Repeated measures MANOVA showed that ACTH secretion during the first half of the night was reduced by the lower dose of NPY only (F = 8.7, p<0.05), while cortisol secretion during the second half of the night was reduced regardless of the dose (F = 7.9, p<0.05). Regardless of the dose, NPY enhanced sleep period time and stage 2 sleep (F = 12.8 and 5.4, each p<0.05), and also reduced sleep latency and time awake (F = 4.9 and 4.4, each p<0.05) and modulated REM sleep. In summary, NPY promotes sleep and inhibits the hypothalamo-pituitary-adrenocortical (HPA) axis in humans, pointing to a possible role of NPY agonists for the development of novel treatment strategies for affective disorders.

Effects of hormones on sleep.

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.

Cortisol enhances non-REM sleep and growth hormone secretion in elderly subjects.

Aging is accompanied by a continuous decline in slow wave sleep (SWS) and in growth hormone (GH) secretion, particularly during the sleeping period. Because short-term pulsatile administration of cortisol increases GH release and SWS in young adults, we wondered whether similar effects can be induced also in elderly men. Hourly injections of cortisol between 1700 and 600 h increased stage 2 and SWS and decreased rapid eye movement sleep. Spectral analysis revealed significant increases in delta and theta power. Cortisol infusions increased the GH secretion prior to sleep onset, but remained largely unchanged during sleep. Thus, sleep EEG and GH release are modulated by cortisol administration in a manner similar to that in young subjects, but to a lesser extent. The stimulatory effect of cortisol on both GH release and SWS points to a mechanism involving glucocorticoid-enhanced production and release of GH-releasing hormone that activates pituitary GH release and simultaneously antagonizes the effects of corticotropin-releasing hormone and somatostatin.

Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study.

To assess the significance of GABAA-receptor heterogeneity, which is based on a family of at least 15 subunits, the cellular localization and subunit composition of GABAA-receptor subtypes were analyzed immunohistochemically in the rat spinal cord. The distribution of subunits alpha 1, alpha 2, alpha 3, alpha 5, beta 2,3, and gamma 2 was investigated with subunit-specific antibodies, and their colocalization within individual neurons was visualized by double-immunofluorescence staining. The results reveal a widespread expression of the subunits, alpha 3, beta 2,3, and gamma 2 in the spinal cord, whereas the three other alpha subunits displayed a more restricted, lamina-specific distribution. The alpha 1 and alpha 5 subunits were most abundant in the intermediate zone, whereas the alpha 2 subunit was predominant in the superficial layers of the dorsal horn and in somatic and preganglionic motoneurons. From colocalization studies, seven subunit combinations could be identified (alpha 3/beta 2,3/gamma 2; alpha 2/beta 2,3/gamma 2; alpha 1/beta 2,3/gamma 2; alpha 5/beta 2,3/gamma 2; alpha 1/alpha 5/beta 2,3/gamma 2; alpha 2/gamma 2; alpha 2/alpha 5/gamma 2) that correspond presumably to distinct receptor subtypes. Although most neurons expressed the subunit triplet alpha x/beta 2,3/gamma 2, the beta 2,3 subunits could not be detected in motoneurons that may thus possess "atypical" receptor subtypes (alpha 2/gamma 2 and alpha 2/alpha 5/gamma 2). ON the subcellular level, aggregates of immunoreactivity, suggestive of postsynaptic GABAA receptors, typically were seen on the surface of neuronal somata and proximal dendrites. In addition, an intense diffuse staining was observed in laminae I--III for the subunits alpha 2, alpha 3, beta 2,3, and gamma 2, presumably localized on primary afferent terminals. The localization of GABAA-receptor subtypes in distinct laminar compartments of the spinal cord suggests that GABAA-receptor heterogeneity is of relevance for the modulation of sensory inputs, nociception, and motor control at segmental levels.

Inhibitory neurotransmission in rat spinal cord: co-localization of glycine- and GABAA-receptors at GABAergic synaptic contacts demonstrated by triple immunofluorescence staining.

Synaptic inhibition in rat spinal cord is mediated by the amino acids gamma-aminobutyric acid (GABA) and glycine. Most spinal cord neurons respond to both neurotransmitters, suggesting co-expression of GABAA- and strychnine-sensitive glycine-receptors in individual cells. While the distribution of glycine-receptors has been extensively characterized, much less is known about the cellular localization of GABAA-receptors in spinal cord neurons. In the present study, the distribution of GABAA-receptors was analyzed immunohistochemically with a subunit-specific antiserum recognizing the alpha 1-subunit. Their co-localization with glycine-receptors and their apposition to GABAergic axon terminals were assessed by confocal laser microscopy in sections processed for double- and triple-immunofluorescence staining, using a monoclonal antibody against the 93 kDa glycine-receptor-associated protein, gephyrin, and an antiserum to glutamic acid decarboxylase. Staining for the GABAA-receptor alpha 1-subunit decorated the soma and dendrites of numerous neurons in laminae III-VIII and X of the spinal cord, revealing their morphology in clear detail. By contrast, laminae II and IX contained little immunoreactivity for these GABAA-receptors. Double-immunofluorescence staining showed that most GABAA-receptor-positive cells in layers III-VIII and X also exhibited a prominent glycine-receptor immunoreactivity. Both types of receptors had very similar distribution patterns in the cell membrane and were frequently co-localized in sites apposed to GABAergic axon terminals. These results indicate that GABAA- and glycine-receptors may co-exist within single postsynaptic densities, suggesting a possible synergism in the action of GABA and glycine in spinal cord neurons.