Improved Mobility, Cognition, and Disease Severity in Corticobasal Degeneration of an African American Man After 12 Weeks of Adapted Tango: A Case Study.

Corticobasal degeneration (CBD) has no available treatment to slow disease progression and generally resists drug therapy. Corticobasal degeneration has symptoms and decreased quality of life similar to Parkinson disease. Adapted Tango, a successful rehabilitation for Parkinson, may address CBD. A 63-yr-old African American man with CBD (alias: YD; CBD duration = 2 yrs) was evaluated for motor, cognitive, and psychosocial function before, immediately after, 1 mo after, and 6 mos after 12 wks of 20, biweekly 90-min adapted-tango lessons. After intervention, disease-related motor symptoms improved and YD reported fewer problems in nonmotor experiences of daily living, which include mood, cognition, pain, fatigue, etc. Motor symptoms remained above baseline at 6-mo posttest. YD's balance confidence improved after intervention but declined below baseline at 6-mo posttest. Quality of life was maintained despite worsened depression. YD improved or maintained executive function, and visuospatial function and attention at posttest and 1-mo posttest. At posttest, YD maintained mobility and improved on dynamic balance. At 1-mo posttest, most mobility measures had improved relative to baseline. However, YD showed executive function and overall motor decline 6 mos after intervention. Adapted tango may have temporarily slowed disease progression and improved or maintained mobility and cognition. Gains were poorly maintained after 6 mos. Further study is warranted.

[Psychosis Associated With Fahr's Syndrome: A Case Report]. / Psicosis asociada con síndrome de Fahr: informe de un caso.

INTRODUCTION: Fahr syndrome (SF) is a rare neurological disorder, characterized by abnormal deposition of calcium in brain areas that control movement. OBJECTIVE: The case is presented of a 41-year-old female with a convulsive syndrome, psychotic disorder, neurocognitive disorde,r and intellectual disability associated with bilateral brain calcifications and altered calcium/phosphorus metabolism in the context of hypoparathyroidism. METHOD: Case report. RESULTS: The calcifications found in the patient could be the cause of psychotic symptoms and cognitive impairment. Diagnostic imaging, laboratory tests, psychiatric and neuropsychological assessments are presented. The clinical presentation of this case is compared with similar ones reported in the literature. Therapeutic approaches and clinical outcomes are described. CONCLUSIONS: Fahr's syndrome should be suspected in patients with neuropsychiatric disorders and seizures. Neuroimaging studies, and the determining of phosphorus and calcium metabolism and parathyroid hormone levels are important in this type of patient.

[Somatotopy in the basal ganglia].

Somatotopy is a fundamental concept that is essential for the understanding of the functions of the brain. Here, I have described somatotopy in the basal ganglia that comprise the striatum, subthalamic nucleus, globus pallidus, and substantia nigra. Projections from the motor cortical subregions that represent different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding subregions of the motor cortices but also to the active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopy can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through a cortico-basal ganglia loop. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders such as Parkinson disease and dystonia.

Rotarod impairment: catalepsy-like screening test for antipsychotic side effects.

Extrapyramidal motoric symptoms are casual side effects under antipsychotic medication. New generation antipsychotics are expected to have a reduced risk due to different receptor affinities. Here, haloperidol and the new generation antipsychotics, risperidone, amisulpride, and aripiprazole, were examined with both catalepsy test and rotarod performance test to screen for their usability in mice. Mice treated with haloperidol, risperidone, and aripiprazole showed dose and time-dependent impairment. Amisulpride-treated mice showed no signs of catalepsy. Catalepsy test and rotarod performance test were useful methods to detect side effects of both generation antipsychotics. Catalepsy test provided more specificity whereas the rotarod test provided higher degree of sensitivity to motor impairment including catalepsy.

2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family.

Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary material. The online version of this article (doi:10.1007/s12031-009-9287-3) contains supplementary material, which is available to authorized users.

Abnormal resting-state functional connectivity patterns of the putamen in medication-naïve children with attention deficit hyperactivity disorder.

Structural and functional alterations of the putamen have been reported in patients with attention deficit hyperactivity disorder (ADHD), but the functional relationships between this area and other brain regions are seldom explored. In the present study, seed-based correlation analyses were performed in the resting-state functional magnetic resonance imaging (fMRI) data to examine the differences in functional connectivity of the putamen between medication-naïve children with ADHD and normal children. Positive functional connectivity with the putamen-ROIs was seen in bilateral sensorimotor area, prefrontal cortex, insula, superior temporal gyrus and subcortical regions and negative functional connectivity was located in bilateral parietal and occipital cortex as well as clusters in the frontal, middle temporal cortex and cerebellum. Group comparison showed that decreases in functional connectivity with the putamen-ROIs were observed in ADHD relative to the controls, except for the right globus pallidus/thalamus, which showed increased positive connectivity with left putamen-ROI. For children with ADHD, areas exhibiting decreased positive functional connectivity with left putamen-ROI were seen in right frontal and limbic regions, and regions showing decreased negative connectivity with the putamen-ROIs were observed in areas belonging to the default mode network (for left putamen-ROI, including right cerebellum and right temporal lobe; for right putamen-ROI, including left cerebellum and right precuneus). The above results suggest that abnormal functional relationships between the putamen and the cortical-striatal-thalamic circuits as well as the default mode network may underlie the pathological basis of ADHD.

Non-motor basal ganglia functions: a review and proposal for a model of sensory predictability in auditory language perception.

While the primary function of the basal ganglia (BG) is linked to motor behaviour, several investigations of non-motor behaviour allocate cognitive and language-specific functions to the BG. What may such seemingly discrepant functions have in common? Some neurophysiologic theories of motor behaviour assign temporal sequencing, others the sequencing of general cognitive patterns to the BG. Turning to auditory language perception and syntax in particular, one may consider syntactic processing as a hierarchical sequencing phenomenon. Furthermore, previous data have shown that if events are predictable, the processing of successively following events in a sequence is facilitated. We propose that sequencing is closely linked to the perception of predictable cues (regular beats, meter, temporal chunks etc.). If this is the case, syntactic processing should rely on the extraction of predictable cues in auditory language perception. Consequently, dysfunctional extraction of such cues in BG patients should then lead to secondary deficits in syntactic processing as evidenced in recent behavioural and electrophysiological evidence (ERP). The fact that such "secondary syntactic deficits" can be compensated by external and speech inherent predictable cues permits two conclusions: (i) syntactic deficits in BG patients are epiphenomenal, and (ii) sequencing dysfunctions of the pre-supplementary motor area (SMA)-BG circuit may be compensated by increased influence of the cerebellar-thalamic-pre-SMA pathway. In the current review we elaborate on this possibility drawing comparisons to similar proposals in motor and language production.

Striatal plasticity and basal ganglia circuit function.

The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways, which are distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function.

[The use of nifedipine as a corrector of extrapyramidal side-effects of classical neuroleptics].

The aim of the article was to study efficacy and safety of nifedipine in the correction of extrapyramidal side-effects emerged during conventional neuroleptics therapy. Fifty-one patients diagnosed with paranoid schizophrenia received haloperidol in combination with nifedipine (25 patients) or haloperidol only (26 patients) during 26 weeks. Dynamics of psychopathological symptoms and extrapyramidal disorders were measured with PANSS, CGI, BARS, SARS and AIMS. Patients receiving haloperidol in combination with nifedipine had the lower AIMS scores indicating appearances of dyskinesia and less marked (on the trend to statistical significance) SARS scores measuring parkinsonian symptoms as compared to patients receiving monotherapy with haloperidol. The administration of nifedipine in combination with haloperidol did not reduce the therapeutic efficacy of the latter and did not lead to the increase of side-effects. The data obtained suggest that nifedipine may be used as a perspective corrector of extrapyramidal disorders caused by classical neuroleptics.

Diffusion tensor imaging in infants with basal ganglia-thalamic lesions.

We performed diffusion tensor imaging in two infants with neonatal hypoxic-ischemic encephalopathy. MRI revealed basal ganglia-thalamic lesions in both patients during the neonatal period. Patient 1 had severe neurological sequelae, whereas patient 2 achieved normal development. Conventional MRI at 12 months of age showed abnormal high-intensity areas in bilateral basal ganglia and thalami in patient 1, whereas no abnormal intensities were recognized in patient 2. Diffusion tensor tractography demonstrated poor depiction of white matter tracts above the level of centrum semiovale in patient 1. Region of interest analysis showed that fractional anisotropy of white matter of centrum semiovale and deep white matter was markedly reduced in patient 1 compared with patient 2, although apparent diffusion coefficient was not largely different between them. Our study suggested that abnormalities of diffusion property will be more widely present than those of conventional MRI. Diffusion tensor imaging will be useful to detect white matter abnormalities in normal-appearing white matter on conventional MRI.

Vitamin A supplementation induces a prooxidative state in the striatum and impairs locomotory and exploratory activity of adult rats.

Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.

Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels.

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps.

Number processing and basal ganglia dysfunction: a single case study.

Numerical processing has never been investigated in a case of Fahr's disease (FD) and only rarely in cases of basal ganglia dysfunction. The study describes the cognitive decline of a pre-morbidly high-functioning patient (medical doctor) affected by FD and his difficulties in number processing. A MRI scan revealed bilateral calcifications in the basal ganglia and a brain PET showed a massive reduction of glucose metabolism in the basal ganglia and both frontal lobes, but no other brain abnormalities. The patient's cognitive deficits included impairments in problem solving, in cognitive set shifting and in mental flexibility, as well as in verbal memory. These deficits are attributed to the disruption of the dorsolateral prefrontal circuit involving the basal ganglia. In number processing, the patient showed a severe deficit in the retrieval of multiplication facts, deficits in all tasks of numerical problem solving and in the execution of complex procedures. Importantly, he also showed a dense deficit in conceptual knowledge, which concerned all test conditions and all operations. The findings confirm the predictions of the triple code model in so far, as a disruption of cortico-subcortical loops involving the basal-ganglia may lead to specific deficits in fact retrieval. However, no verbal deficit, as assumed in the triple code model and reported in similar cases, could be observed. The present findings further add to current knowledge on numerical processing, showing how fronto-executive dysfunction may disrupt conceptual understanding of arithmetic. This study shows that not only parietal lesions may lead to severe deficits in conceptual understanding, but that basal ganglia lesions leading to frontal dysfunction may have a devastating effect.

Combined treatment of quetiapine with haloperidol in animal models of antipsychotic effect and extrapyramidal side effects: comparison with risperidone and chlorpromazine.

RATIONALE: Quetiapine, an atypical neuroleptic, has beneficial antipsychotic effects in schizophrenic patients, but with a lower incidence of extrapyramidal symptoms (EPS) compared with typical antipsychotics. While typical antipsychotics are often switched to atypical agents when adverse effects become limiting, there is little preclinical information to support this strategy, both in terms of efficacy and side effects. OBJECTIVES: The antipsychotic effects and EPS during concomitant administration of quetiapine with haloperidol, a typical antipsychotic agent, were evaluated in mice and compared with chlorpromazine and risperidone. METHODS: We first investigated the antipsychotic effects and EPS liability of quetiapine, risperidone, chlorpromazine, and haloperidol when administered alone to select optimal doses for subsequent combination studies. The second study was designed to evaluate the antipsychotic efficacy and EPS profile of concomitant administration of quetiapine, risperidone, or chlorpromazine with haloperidol. Antipsychotic effects were evaluated with the methamphetamine-induced hyperlocomotion test, and EPS liability was evaluated in a catalepsy-induction model. RESULTS: Quetiapine, risperidone, chlorpromazine, and haloperidol dose-dependently reduced methamphetamine-induced hyperlocomotion, with ED50 values of 5.6, 0.020, 1.8, 0.035 mg/kg, respectively. In the catalepsy test, quetiapine only weakly induced catalepsy at the highest dose of 100 mg/kg, whereas risperidone, chlorpromazine, and haloperidol dose-dependently induced catalepsy with ED50 values of 0.25, 4.6, and 0.10 mg/kg, respectively. While the combination of quetiapine (6 mg/kg) and haloperidol (0.04 mg/kg) significantly reduced methamphetamine-induced hyperlocomotion in comparison with haloperidol alone, quetiapine (10, 32 mg/kg) plus haloperidol did not potentiate the cataleptogenic activity of haloperidol. In contrast, risperidone (0.1, 0.32 mg/kg) or chlorpromazine (3.2 mg/kg) significantly augmented catalepsy induced by haloperidol. Catalepsy induced by co-administration of quetiapine (10 mg/kg) and haloperidol (0.1 mg/kg) was significantly potentiated by WAY100635, a 5-HT1A antagonist, and catalepsy induced by co-administration of risperidone (0.1 mg/kg) and haloperidol (0.1 mg/kg) was significantly antagonized by 8-OH-DPAT, a 5-HT1A agonist. CONCLUSION: The present study demonstrated that the combined administration of quetiapine with haloperidol did not aggravate EPS, possibly because of its affinity for 5-HT1A receptors. This finding may have the clinical implication that quetiapine could provide a successful regimen in switching from typical antipsychotic agents in the symptom management of schizophrenia, or even in adjunctive therapy with other antipsychotic agents.

[The currently accepted pathophysiological model underlying surgical management of Parkinson disease]. / Patofizjologiczne podstawy operacyjnego leczenia choroby Parkinsona.

Among all the extrapiramidal movement disorders Parkinson's disease (PD) is the one most often submitted to neurosurgical treatment. Technical advances in neurosurgery, neuroimaging and neurophysiology, as well as shortcomings of chronic Levodopa medication (i.e. on/off fluctuations, violent dyskinesia and painful dystonia) have greatly contributed to the renewed interest in the surgical treatment of PD. The attainment of a better understanding of the basal ganglia function and of PD pathophysiology has also encouraged centers to treat Parkinson's disease in recent years. This article presents the current model of PD and the rationale for using GPi, thalamus and STN as target sites in stereotactic surgery.

Electrical stimulation of the brain in Wilson-Konovalov hepatocerebral dystrophy (a neuromorphological and neurophysiological analysis).

Stereotaxic surgery was performed in 27 patients. Complete elimination of or significant reductions in hyperkinesia were obtained in 17 cases; five patients died. There was no correlation between the severity of clinical manifestations of hepatocellular dystrophy and the relatively normal quantitative measures of cortical and subcortical biopotentials, which were produced on a background of microstructural changes affecting neurons in these regions. It is suggested that qualitative significance of these biopotentials is that they carry an excess pathological spike activity resulting in hyperkinesia. This is supported by the fact that hyperkinesia was suppressed after surgical destruction of the ventrolateral nucleus of the thalamus and subthalamic structures.

[Cerebral MRI and evoked potentials in Wilson disease. Comparison of findings in patients with neurological follow-up]. / Zerebrales MRT und evozierte Potenziale bei Morbus Wilson. Gegenüberstellung von Befunden bei Patienten mit neurologischer Verlaufsform.

Wilson's disease is caused by toxic copper accumulation, which leads predominantly to hepatic and basal ganglia damage. Characteristic findings in MRI and electrophysiologic examinations are described according to the occurrence of neurological symptoms. In the present study, 28 patients suffering from Wilson's disease (neurological type) were investigated. The results of MRI are compared with abnormalities of evoked potentials (BAEP, MSEP, T-VEP, MEP). All patients show hypodensities in the basal ganglial area (putamen and GI. pallidus) regularly combined with atrophy of the cerebrum and cerebellum in MRI. Signal abnormalities in the mesencephalic region (46% occurrence) and Nc. dentatus (36% occurrence) are combined with the other findings in variable patterns. Only slight changes are found in the pontine region. BAEP are disturbed in 71% of all cases and MSEP in 46%. Combined abnormalities of BAEP and MSEP were found in 39%. Pathological values occurred with a lower frequency in T-VEP (36%) and MEP (39%). The comparison of MRI findings with electrophysiological data done separately for each patient reveals no strong correlation between both methods. Individual MRI findings do not correspond with the patterns of disturbed evoked potentials and vice versa. Therefore we conclude that these methods, MRI and electrophysiological evaluation, supplement each other. Magnetic resonance imaging and electrophysiological evaluation should be performed simultaneously for therapy monitoring.

[The pathophysiological basis of dystonia]. / Bases fisiopatológicas de la distonía.

OBJECTIVE: We review the mechanisms that may involved in the pathophysiology of dystonia. DEVELOPMENT: The role of basal ganglia, spinal and brainstem interneurons, and primary motor cortex in dystonia will be discussed. Abnormalities in the discharge pattern of internal pallidum or thalamus, secondary to basal ganglia disorders might be the cause of disbalance between excitatory and inhibitory mechanisms in motor cortex. Other factors such as excessive repetition of a movement or abnormal sensory afferent discharges may be participating in cortical reorganization. CONCLUSIONS: Overlapping of the cortical representation of dystonic muscles due to enlargement of cortical maps could explain overflow and co-contraction phenomena. The study of the exact role of these factors in each type of dystonia is a challenge for the future that opens the door for new therapeutic approaches.