Neural plasticity: The substratum of music-based interventions in neurorehabilitation.

BACKGROUND: The plastic nature of the human brain lends itself to experience and training-based structural changes leading to functional recovery. Music, with its multimodal activation of the brain, serves as a useful model for neurorehabilitation through neuroplastic changes in dysfunctional or impaired networks. Neurologic Music Therapy (NMT) contributes to the field of neurorehabilitation using this rationale. OBJECTIVE: The purpose of this article is to present a discourse on the concept of neuroplasticity and music-based neuroplasticity through the techniques of NMT in the domain of neurological rehabilitation. METHODS: The article draws on observations and findings made by researchers in the areas of neuroplasticity, music-based neuroplastic changes, NMT in neurological disorders and the implication of further research in this field. RESULTS: A commentary on previous research reveal that interventions based on the NMT paradigm have been successfully used to train neural networks using music-based tasks and paradigms which have been explained to have cross-modal effects on sensorimotor, language and cognitive and affective functions. CONCLUSIONS: Multimodal gains using music-based interventions highlight the brain plasticity inducing function of music. Individual differences do play a predictive role in neurological gains associated with such interventions. This area deserves further exploration and application-based studies.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

A 10% blood pressure drop from baseline during mechanical thrombectomy for stroke is strongly associated with worse neurological outcomes.

BACKGROUND: Mechanical thrombectomy (MT) for acute ischemic stroke can be performed under local anesthesia, with or without conscious sedation (CS), or under general anesthesia (GA). The hemodynamic consequence of anesthetic drugs may explain why GA may be associated with worse outcomes. We evaluated the association between hypotension duration during MT and the 90 day functional outcome under both anesthetic regimens. METHODS: Patients were included in this retrospective study if they had an ischemic stroke treated by MT under GA or CS. The main exposure variable was the time below 90% of the reference value of arterial pressure measured before MT. The primary outcome was poor functional outcome defined as a 90 day modified Rankin Score ≥3. RESULTS: 371 patients were included in the study. GA was performed in 42%. A linear association between the duration of arterial hypotension and outcome was observed. The odds ratio for poor functional outcome of 10 min under 90% of the baseline mean arterial pressure was 1.13 (95% CI 1.06 to 1.21) without adjustment and 1.11 (95% CI 1.02 to 1.21) after adjustment for confounding factors. The functional outcome was poorer for patients treated under GA compared with CS, but the association with the depth of hypotension remained similar under both conditions. CONCLUSION: In this study, we observed a linear association between the duration of hypotension during MT and the functional outcome at 90 days. An aggressive and personalized strategy for the treatment of hypotension should be considered. Further trials should be conducted to address this question.

Associations between brain structural networks and neurological soft signs in healthy adults.

Neurological soft signs (NSS), as minor neurological deficits, have been identified in several psychiatric disorders, especially in schizophrenia. However, it's unclear how the neuropathological processes of the disease affect NSS related brain morphological changes and whether it is confounded by the use of medication. As NSS also exist in healthy people, the potential confounding effects of psychopathology or medication will be excluded if NSS are investigated in healthy people. Therefore, we applied a novel multivariate approach, source-based morphometry (SBM), to study structural networks in relation to NSS in healthy adults based on structural magnetic resonance imaging (MRI) data. The Heidelberg Scale was applied to evaluate NSS. Using SBM, we constructed structural networks and investigated their associations with NSS in healthy adults. Six grey matter (GM) structural networks were identified. Sensory integration subscores were associated with the cerebellar component and the cortico-basal ganglia-thalamic component. Motor coordination subscores and total NSS scores were associated with the sensorimotor component. The present findings indicated that structural network abnormalities in cerebellar, subcortical and cortical sensorimotor areas contribute to NSS performance in healthy adults.

Brain imaging of locomotion in neurological conditions.

Impaired locomotion is a frequent and major source of disability in patients with neurological conditions. Different neuroimaging methods have been used to understand the brain substrates of locomotion in various neurological diseases (mainly in Parkinson's disease) during actual walking, and while resting (using mental imagery of gait, or brain-behavior correlation analyses). These studies, using structural (i.e., MRI) or functional (i.e., functional MRI or functional near infra-red spectroscopy) brain imaging, electrophysiology (i.e., EEG), non-invasive brain stimulation (i.e., transcranial magnetic stimulation, or transcranial direct current stimulation) or molecular imaging methods (i.e., PET, or SPECT) reveal extended brain networks involving both grey and white matters in key cortical (i.e., prefrontal cortex) and subcortical (basal ganglia and cerebellum) regions associated with locomotion. However, the specific roles of the various pathophysiological mechanisms encountered in each neurological condition on the phenotype of gait disorders still remains unclear. After reviewing the results of individual brain imaging techniques across the common neurological conditions, such as Parkinson's disease, dementia, stroke, or multiple sclerosis, we will discuss how the development of new imaging techniques and computational analyses that integrate multivariate correlations in "large enough datasets" might help to understand how individual pathophysiological mechanisms express clinically as an abnormal gait. Finally, we will explore how these new analytic methods could drive our rehabilitative strategies.

Theranostical application of nanomedicine for treating central nervous system disorders.

The primary reason for the failure of traditional medicine in treating the disorders of the central nervous system (CNS) is the obstruction to traverse the blood-brain barrier (BBB). Due to the unique physiochemical properties of nanoparticles, they can preferably help deliver drugs passing through the BBB. Researchers have been investigating the capacity of multifunctional nanomaterials as theranostical agents. However, some of the studies have reported controversial results, which might be due to different schematic designs, including size, surface charge, and shape. This review summarizes the applications of nanoparticles to overcome the BBB or contribute to improving the diagnostic and therapeutic effects in CNS diseases.

Neurocircuitry of impaired affective sound processing: A clinical disorders perspective.

Decoding affective meaning from sensory information is central to accurate and adaptive behavior in many natural and social contexts. Human vocalizations (speech and non-speech), environmental sounds (e.g. thunder, noise, or animal sounds) and human-produced sounds (e.g. technical sounds or music) can carry a wealth of important aversive, threatening, appealing, or pleasurable affective information that sometimes implicitly influences and guides our behavior. A deficit in processing such affective information is detrimental to adaptive environmental behavior, psychological well-being, and social interactive abilities. These deficits can originate from a diversity of psychiatric and neurological disorders, and are associated with neural dysfunctions across largely distributed brain networks. Recent neuroimaging studies in psychiatric and neurological patients outline the cortical and subcortical neurocircuitry of the complimentary and differential functional roles for affective sound processing. This points to and confirms a recently proposed distributed network rather than a single brain region underlying affective sound processing, and highlights the notion of a multi-functional process that can be differentially impaired in clinical disorders.

Effect of Chinese Herbal Medicine on Molecular Imaging of Neurological Disorders.

Chinese herbal medicine has been used to treat a wide variety of neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. However, its mechanism behind the effectiveness remains unclear. Recently, molecular imaging technology has been applied for this purpose, since it can assess the cellular or molecular function in a living subject by using specific imaging probes and/or radioactive tracers, which enable efficient analysis and monitoring the therapeutic response repetitively. This chapter reviews the in vivo functional and metabolic changes after administration of Chinese herbal medicine in various neurological disorders and provides perspectives on the future evaluations of therapeutic response of Chinese herbal medicine.

News and views on in-vivo imaging of neurotransmission using PET and MRI.

Molecular neuroimaging with PET is an integrated tool in psychiatry research and drug-development for as long as this modality has been available, in particular for studying neurotransmission and endogenous neurotransmitter release. Pharmacologic, behavioral and other types of challenges are currently applied to induce changes in neurochemical levels that can be inferred through their effects on changes in receptor binding and related outcome measures. Based on the availability of tracers that are sensitive for measuring neurotransmitter release these experiments have focused on the brain's dopamine system, while recent developments have extended those studies to other targets such as the serotonin or choline system. With the introduction of hybrid, truly simultaneous PET/MRI systems, in-vivo imaging of the dynamics of neuroreceptor signal transmission in the brain using PET and functional MRI (fMRI) has become possible. fMRI has the ability to provide information about the effects of receptor function that are complementary to the PET measurement. Dynamic acquisition of both PET and fMRI signals enables not only an in-vivo real-time assessment of neurotransmitter or drug binding to receptors but also dynamic receptor adaptations and receptor-specific neurotransmission. While fMRI temporal resolution is comparatively fast in relation to PET, the timescale of observable biological processes is highly dependent on the kinetics of radiotracers and study design. Overall, the combination of the specificity of PET radiotracers to neuroreceptors, fMRI signal as a functional readout and integrated study design promises to expand our understanding of the location, propagation and connections of brain activity in health and disease.

Sedation During Surgery for Movement Disorders and Perioperative Neurologic Complications: An Observational Study Comparing Local Anesthesia, Remifentanil, and Dexmedetomidine.

BACKGROUND: The anesthetic management of patients requiring surgery for movement disorders needs to balance microrecording quality and patient cooperation with safety and comfort. Anesthetics can alter microrecording, although the effect on outcome is debatable. They also provide a rested and cooperative patient and minimize complications such as intracranial hemorrhage by providing better hemodynamic control. Most teams use local anesthesia with monitored anesthesia care or conscious sedation with propofol. Recently, dexmedetomidine has emerged as an alternative that, at low doses, does not affect microrecording, and that does not impair respiratory drive. METHODS: In the past 15 years, we have used in our institution local anesthesia, remifentanil, or dexmedetomidine sedation. We compared functional outcome and rate of complications in a group of 145 patients with similar characteristics. RESULTS: We found 5 (3.4%) intracranial hemorrhages. Two (1.4%) were symptomatic. The remifentanil group had the highest risk of having systolic blood pressure >160 mm Hg during surgery (odds ratio [OR], 2.8; 95% confidence interval [CI], 0.9-9.9), whereas the dexmedetomidine group had the lowest (OR, 0.7; 95% CI, 0.2-1.8), compared with the local anesthesia group. Surgical time was shortest with dexmedetomidine (mean, 283 minutes) and longest with local anesthesia only (mean, 328 minutes). Functional outcome (Unified Parkinson's Disease Rating Scale, Part III motor component scale) was similar among groups. The dexmedetomidine group had a statistically significant lower risk of perioperative neurologic events compared with the local anesthesia group (OR, 0.09; 95% CI, 0.002-0.68). CONCLUSIONS: Sedation can be used safely without affecting outcome, and dexmedetomidine provides better hemodynamic management. Clinical significance remains unclear and larger studies need to be undertaken.

Functional neurological disorders: mechanisms and treatment.

Functional neurological disorders are common problems in neurologic practice. In the past decade there has been an increasing interest in this group of disorders both from a clinical as well as research point of view. In this review, we highlight some of the most salient and exciting publications from recent years focusing especially on new findings illuminating mechanism and studies examining treatment.

Positron emitting tracers in pre-clinical drug development.

Molecular imaging tools such as Positron Emission Tomography (PET) are increasingly being used in the drug development process. The unrivaled sensitivity of PET coupled with a solid experience in developing highly targeted molecular probes makes this technique a very valuable tool at all stages from pre-clinical development to the clinical phases. Positron emitting tracers allow us to measure, quantitatively, molecular processes and interactions between a candidate drug and its molecular targets. This information can save time and money by directing development towards the most promising compounds and excluding molecules with unfavorable properties that would otherwise only be recognized as failures in latter stages of the process. In this paper we review the application of positron emitting tracers in the pre-clinical stages of the drug development process in the areas of oncology, cardiology, neurosciences and inflammatory diseases. PET tracers provide an important support for drug development in the areas of: discovery of new drug targets, clarification of pathophysiology, identification of potential drug candidates and validation of drug effectiveness, as well as the evaluation of pharmacokinetic and pharmacodynamic parameters in vivo.

A prospective, randomized, controlled trial comparing ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery for postoperative neurological symptoms.

BACKGROUND: Visualization with ultrasound during regional anesthesia may reduce the risk of intraneural injection and subsequent neurological symptoms but has not been formally assessed. Thus, we performed this randomized clinical trial comparing ultrasound versus nerve stimulator-guided interscalene blocks for shoulder arthroscopy to determine whether ultrasound could reduce the incidence of postoperative neurological symptoms. METHODS: Two hundred thirty patients were randomized to a standardized interscalene block with either ultrasound or nerve stimulator with a 5 cm, 22 g Stimuplex insulated needle with 1.5% mepivacaine with 1:300,000 epinephrine and NaCO3 (1 meq/10 mL). A standardized neurological assessment tool (questionnaire and physical examination) designed by a neurologist was administered before surgery (both components), at approximately 1 wk after surgery (questionnaire), and at approximately 4-6 weeks after surgery (both components). Diagnosis of postoperative neurological symptoms was determined by a neurologist blinded to block technique. RESULTS: Two hundred nineteen patients were evaluated. Use of ultrasound decreased the number of needle passes for block performance (1 vs 3, median, P < 0.001), enhanced motor block at the 5-min assessment (P = 0.04) but did not decrease block performance time (5 min for both). No patient required conversion to general anesthesia for failed block, and patient satisfaction was similar in both groups (96% nerve stimulator and 92% ultrasound). The incidence of postoperative neurological symptoms was similar at 1 wk follow-up with 11% (95% CI of 5%-17%) for nerve stimulator and 8% (95% CI of 3%-13%) for ultrasound and was similar at late follow-up with 7% (95% CI of 3%-12%) for nerve stimulator and 6% (95% CI of 2%-11%) for ultrasound. The severity of postoperative neurological symptoms was similar between groups with a median patient rating of moderate. Symptoms were primarily sensory and consisted of pain, tingling, or paresthesias. CONCLUSIONS: Ultrasound reduced the number of needle passes needed to perform interscalene block and enhanced motor block at the 5 min assessment; however, we did not observe significant differences in block failures, patient satisfaction or incidence, and severity of postoperative neurological symptoms.

The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies.

Histamine neurons are exclusively located in the posterior hypothalamus, and project their fibers to almost all regions of the human brain. Although a significant amount of research has been done to clarify the functions of the histaminergic neuron system in animals, a few studies have been reported on the roles of this system in the human brain. In past studies, we have been able to clarify some of the functions of histamine neurons using different methods, such as histamine-related gene knockout mice or human positron emission tomography (PET). The histaminergic neuron system is known to modulate wakefulness, the sleep-wake cycle, appetite control, learning, memory and emotion. Accordingly we have proposed that histamine neurons have a dual effect on the CNS, with both stimulatory and suppressive actions. As a stimulator, neuronal histamine is one of the most important systems that stimulate and maintain wakefulness. Brain histamine also functions as a suppressor in bioprotection against various noxious and unfavorable stimuli of convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress susceptibility. This review summarizes our works on the functions of histamine neurons using human PET studies, including the development of radiolabeled tracers for histamine H1 receptors (H1R: (11)C-doxepin and (11)C-pyrilamine), PET measurements of H1R in depression, schizophrenia, and Alzheimer's disease (AD), and studies on the sedative effects of antihistamines using H(2)(15)O and H1R occupancy in the human brain. These molecular and functional PET studies in humans are useful for drug development in this millennium.

[Neurological explorations in Nuclear Medicine. A Spanish survey]. / Exploraciones neurológicas en Medicina Nuclear. Encuesta española.

A representative Nuclear Medicine Service in Spain has two or three gammacameras. It performs neurologic studies one or two days at week wich account 2,1% of total workload. Brain Perfusion SPECT, specially in cognitive disorders, is the most frequent application. Neurooncology has a lower but established relevance. Neuroreceptors imaging are increasing in the last months. Emission tomography is obtained using a double-headed camera fitted with high-resolution parallel hole collimators and a half an hour total acquisition time. Datasets are reconstructed by filtered backprojection with Butterworth or Metz filtres. Images are visually interpreted with comparison to MRI and/or CT findings.

Recent and future evolutions in NeuroSPECT with particular emphasis on the synergistic use and fusion of imaging modalities.

Recent and future evolutions in neuroSPECT apply to radiopharmaceuticals techniques and the synergistic use of different imaging modalities in the work-up of neurological disorders. The introduction of Technetium labelled perfusion tracers, which could pass the intact blood-brain barrier, together with the implementation of the tomographic principle, by making the conventional gamma camera rotating, enabled estimation of regional cerebral blood flow and indirectly of local brain metabolism. In addition at present Thallium-201 and Tc-99m sestaMIBI allow functional detection of viable tumor tissue, without interference from previous surgery or radiotherapy as seen using CT-scan or MRI. In neurology this has led to the recognition of SPECT by the American Academy of Neurology (Therapeutics and technology subcommittee) as an established or promising tool in major neurological disorders such as dementia, stroke and epilepsy, while other domains such as brain oncology are considered investigational. With regard to radiopharmaceuticals, recent evolutions mainly include the development of mostly Iodine-123 labelled receptor ligands, some of which are already commercially available. For instrumentation advances consist e.g. of multidetector systems equipped with fanbeam collimators, attenuation and scatter correction or coincidence detection. Given the present role for nuclear neurology it may be expected that these additional radiopharmaceutical and technical innovations will continue to stimulate the development of SPECT of the brain. The synergistic use of several imaging techniques such as CT, (functional) MRI, source imaging, SPECT and PET represents a multimodal holistic approach to probe cerebral functions for research and clinical purposes. Clinical indications, in which this synergistic use is illustrated include e.g. support of the clinical diagnosis of dementia of the Alzheimer type, presurgical ictal detection of seizure focus, detection of acute ischemia and differential diagnosis between radiation necrosis and brain tumor recurrence. The synergistic use of imaging modalities, optimally applied using image fusion, allows to overcome the intrinsic limitations and to enhance the specific advantages of the different approaches as it leads to increased precision and accuracy, as well for spatial anatomofunctional correlation as for quantification.

Ethylmalonic aciduria: an organic acidemia with CNS involvement and vasculopathy.

Five infants from 3 families, one Egyptian, two Yemeni, are described with a progressive encephalopathy, four of whom have been studied in detail. All patients showed vascular lesions of the skin, characterized by waxing and waning petechiae and ecchymoses. Acrocyanosis was present in three patients. All patients showed retinal lesions characterized by tortuous veins. Protracted diarrhea was not a consistent finding, although they had metabolic crisis in association with diarrhea. They did not show failure to thrive. The neurologic symptoms were indicative of a progressive pyramidal tract disease. Three patients died following sudden emergence of severe basal ganglia, putaminal and head of caudate lesions. In one patient the CT changes in brain were suggestive of infarction. The patients who died manifested pulmonary congestion, or wet lung, and respiratory difficulties during the terminal stage of the disease. In all patients before and during the terminal event, mild-to-moderate hematuria, and in two RBC in CSF, was observed. In one patient there was mild hemoperitoneum at the terminal event. The urine organic acids indicated increased excretion of ethylmalonic, methylsuccinic, glutaric, and adipic acids. The patients invariably showed lactic acidosis, but no ketosis, during and in between the acidotic attacks of the disease. The acylcarnitine profile in blood of two patients showed a pronounced increase in C4 and C5 carnitine esters. In three patients, biopsies from petechiae indicated absence of an immune event, showing only fresh hemorrhage. An immunologic study in one patient was normal for the suppressor:cytotoxic lymphocyte ratio and concentration of interleukin-2 receptor during and in between hemorrhagic attacks. The cytochrome c oxidase activity in fibroblasts was normal. The rate of oxidation of glucose, leucine, isoleucine, valine, propionate and butyrate by fibroblasts was normal. The disease is not responsive to treatment with riboflavin, ascorbic acid, vitamin E, glycine, or carnitine. One patient remained stable on prolonged large doses of methylprednisolone. The biochemical defect leading to ethylmalonic aciduria in this disease remains unknown.

Neuromusculoskeletal thermography: a valuable diagnostic tool?

The use of neuromusculoskeletal thermography is rapidly increasing. Recent studies have begun to document the types of diagnostic and other clinically useful information which may be derived from the procedure. This paper provides a review and summary of current research and a comparison with myelography, computerized tomography, electromyography and clinical and surgical findings in cases of presumed musculoskeletal pain syndromes. The importance of diagnostic sensitivity, specificity, positive and negative predictive value, and accuracy (validity) are discussed. In general, the literature reports high sensitivity and negative predictive value, but lower specificity and positive predictive value. The implications of these findings are examined in regard to clinical case management, with emphasis on potential usefulness to chiropractors. Although thermography appears to be a promising diagnostic tool, there remain a number of threats to the scientific validity of current research which must be accounted for in future work.

Computerized tomography and pure sensory stroke.

We studied three patients fitting the clinical syndrome of "pure sensory" stroke. The abnormalities on computerized tomography (CT) scan differed and included posterior cerebral artery occlusion, lacunar infarct in the thalamocortical pathway, and hemorrhage in the thalamus. These cases were unique in that CT scan abnormalities were found in patients with pure sensory stroke.