A state hospital survey of movement disorders including intention tremor

AimsIn a survey of movement disorders in patients in a State Hospital the finger-nose test was included because of increasing interest in the cerebellum in schizophrenia. It was expected that this would reflect the pathobiology of schizophrenia and be unrelated to the type of medication.BackgroundAbnormalities of movement and involuntary movements have gone from being considered part of schizophrenia to side-effects of medication to now demonstrably present in those who have never taken anti-psychotic medication. Soft neurological signs (SNS) are increased in schizophrenia, unrelated to medication, considered not to indicate brain localization, yet often include the finger-nose test which localizes to the cerebellum.MethodAll available patients in a State Hospital were examined for movement disorders. They were rated on the following scales: Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia (TD), Simpson-Angus Neurological Rating Scale for Parkinsonism (SANRS), Barnes Akathisia Scale (BAS), a Dystonia scale and the finger-nose test.Result250 patients were included, 174 were examined or observed for movement disorder: 120 had no missing data, 54 refused part of the exam. Their mean age was 47, 62% male, 53% black, 26% Hispanic, 17% white.Medication: First Generation Antipsychotic (FGA) 35 (mean CPZ equivalent dose:1177mg), Second Generation Antipsychotic (SGA) 159 (734mg), both FGA and SGA 56 (1907mg), no antipsychotic 3; anticholinergic or amantidine: FGA 57%, SGA 16%, both FGA and SGA: 50%.Tardive Dyskinesia: all 23%, FGA 36%, SGA 25%, both 7%Parkinsonism: all 38%, FGA 43%, SGA 33%, both 34%Akathisia: all 3%, FGA 0%, SGA 4%, both 3%Pseudo-akathisia: FGA 11%, SGA 4%, both13%Dystonia: all 10%, FGA 13%, SGA 11%, both 8%Intention Tremor: all 16%, FGA 0%, SGA 21%, both 16%Half of those with Intention Tremor had Parkinsonism, a third had TD and a half were on anti-Parkinson medication.None of these differences were statistically significant at p = 0.05 though intention tremor did show a trend (p = 0.08). The difference between FGA and SGA only became significant when all movement disorders were added together with those on anticholinergics with no movement disorder.When compared with rates in similar State Hospitals in the 1970s tardive dyskinesia was now half the rate and Parkinsonism about the same.ConclusionOverall rates of movement disorder are not very different between FGA and SGA. The surprise was that intention tremor only occurred with SGAs. Why?

Cerebral Toxocariasis as a Cause of Epilepsy: A Pediatric Case

Toxocarosis is the consequence of human infection by Toxocara spp. larvae and is one of the most common ascarioses, not only in developing countries, but also in the European region, where its prevalence reaches 14%. Due to their particular behavior, children are at higher risk of this parasitic infection, whose clinical features depend on the localization of the Toxocara larvae. Neurotoxocariasis is very uncommon in children and may take different forms depending on the underlying physiopathologic process: immune reaction against the parasite antigens, vasculitis, treatment complications, or, very rarely, brain localization of Toxocara spp. larvae. The association between neurotoxocariasis and the onset of childhood epilepsy has been postulated but is still debated. Moreover, a Toxocara spp. abscess causing epileptic seizures in children has been rarely described, especially in western countries. Hereby we present a 9-year-old patient with a new diagnosis of epilepsy definitely secondary to brain abscess due to the localization of Toxocara canis larvae. Diagnosis was confirmed by neuroimaging and serological test. The successful treatment with albendazole and steroids was documented with a close and long-term clinical and neuroradiological follow-up. Our experience confirms that every case of cryptogenetic epilepsy in children deserves a neuroimaging study and, in case of cystic images, Toxocara serology is mandatory to avoid further unnecessary invasive diagnostic investigations and to set the specific drug therapy.

Forensic neuropsychology: Role and significance in judicial system

Forensic neuropsychology derived from clinical neuropsychology. This area not only relies on neuropsychological approach and practice and principals of brain structure and functions, but also on the contribution of diagnostic methods of brain visualization (neuroimaging). In the last decade, large number of books that deal with this topic has been published, mostly by American authors, just as a Journal of Forensic Neuropsychology dedicated to this field has started issuing. There are more and more demands in the world from judges and lawyers that neuropsychologists should provide services of quantifying and evaluating the severeness of cognitive deficits of respondents. In most cases, it is being asked of neuropsychologist to provide expertise based on clinical observation and results of neuropsychological examinations about the connection of individual cognitive functioning and behavior and special brain localization, as well as to provide the evaluation of the level of cognitive impairments. Unfortunately, official educational and training program in this field doesn't exist in Serbia, so a specific licence is not required. Also, there is a lack of professional organization that would gather forensic neuropsychologists. Practitioners that firstly obtained the status of graduated psychologists and then were educated in the field of clinical neuropsychology are the ones who deal with this area. In our country the role of forensic neuropsychologist is still not recognised enough, just as the possible significance these experts might have in judicial processes isn't. Topics that are being most focused on in the scope of forensic neuropsychology are ethical questions, the evaluation of validity of symptoms with special emphasis on evaluating effort that is being put on examination and the precense of potential malingering, There are significant differences between clinical and forensic neuropsychology. Clinical neuropsychology determines the presence of impairment in cognitive functioning, while the main goal of forensic neuropsychology is to provide answers to the legal questions. That key difference between goals leads to different presumptions, roles, alliances and methods. The results of clinical and forensic examinations are demanded and used by different scientists. Clincal evaluation is mostly demanded by experts who deal with treating and rehabilitating people with neuropsychological impairments or brain injuries, while forensic evaluation is being demanded and used by legal institutions. Efficient use of neuropsychological principles as an answer on forensic questions requires clinical skills, critical thinking and close connection to the scientific principles. With double focus on clinical psychology and neurology, neuropsychologists can contribute to the legal system not only by their understanding of neuroanathomy and neuropathology, but also with their capability to objectively document how neuropathological conditions affect thinking, memory and decision making process, which is, by far, the most important.

Correlated Brain Indexes of Semantic Prediction and Prediction Error: Brain Localization and Category Specificity

With strong and valid predictions, grasping a message is easy, whereas more demanding processing is required in the absence of robust expectations. We here demonstrate that brain correlates of the interplay between prediction and perception mechanisms in the understanding of meaningful sentences. Sentence fragments that strongly predict subsequent words induced anticipatory brain activity preceding the expected words; this potential was absent if context did not strongly predict subsequent words. Subjective reports of certainty about upcoming words and objective corpus-based measures correlated with the size of the anticipatory signal, thus establishing its status as a semantic prediction potential (SPP). Crucially, there was an inverse correlation between the SPP and the N400 brain response. The main cortical generators of SPP and N400 were found in inferior prefrontal cortex and posterior temporal cortex, respectively. Interestingly, sentence meaning was reflected by both measures, with additional category-specific sources of SPPs and N400s falling into parieto-temporo-occipital (visual) and frontocentral (sensorimotor) areas for animal- and tool-related words, respectively. These results show that the well-known brain index of semantic comprehension, N400, has an antecedent with different brain localization but similar semantic discriminatory function. We discuss whether N400 dynamics may causally depend on mechanisms underlying SPP size and sources.

Phosphodiesterase 10A Inhibition Leads to Brain Region-Specific Recovery Based on Stroke Type

Stroke is the leading cause of adult disability. Recovery of function after stroke involves signaling events that are mediated by cAMP and cGMP pathways, such as axonal sprouting, neurogenesis, and synaptic plasticity. cAMP and cGMP are degraded by phosphodiesterases (PDEs), which are differentially expressed in brain regions. PDE10A is highly expressed in the basal ganglia/striatum. We tested a novel PDE10A inhibitor (TAK-063) for its effects on functional recovery. Stroke was produced in mice in the cortex or the striatum. Behavioral recovery was measured to 9 weeks. Tissue outcome measures included analysis of growth factor levels, angiogenesis, neurogenesis, gliogenesis, and inflammation. TAK-063 improved motor recovery after striatal stroke in a dose-related manner, but not in cortical stroke. Recovery of motor function correlated with increases in striatal brain-derived neurotrophic factor. TAK-063 treatment also increased motor system axonal connections. Stroke affects distinct brain regions, with each comprising different cellular and molecular elements. Inhibition of PDE10A improved recovery of function after striatal but not cortical stroke, consistent with its brain localization. This experiment is the first demonstration of brain region-specific enhanced functional recovery after stroke, and indicates that differential molecular signaling between brain regions can be exploited to improve recovery based on stroke subtype.

Visualization of axonal protein allocation in Drosophila with whole-brain localization microscopy

Long-term memory (LTM) formation requires learning-induced protein synthesis in specific neurons and synapses within a neural circuit. Precisely how neural activity allocates new proteins to specific synaptic ensembles, however, remains unknown. We developed a deep-tissue super-resolution imaging tool suitable for single-molecule localization in intact adult Drosophila brain, and focused on the axonal protein allocation in mushroom body (MB), a central neuronal structure involved in olfactory memory formation. We found that insufficient training suppresses LTM formation by inducing the synthesis of vesicular monoamine transporter (VMAT) proteins within a dorsal paired medial (DPM) neuron, which innervates all axonal lobes of the MB. Surprisingly, using our localization microscopy, we found that these learning-induced proteins are distributed only in a subset of DPM axons in specific sectors along the MB lobes. This neural architecture suggests that sector-specific modulation of neural activity from MB neurons gates consolidation of early transient memory into LTM.