Postural Reflexes Research Articles

Effects of galvanic vestibular stimulation on postural limb reflexes and neurons of spinal postural network

Quadrupeds maintain the dorsal side up body orientation due to the activity of the postural control system driven by limb mechanoreceptors. Binaural galvanic vestibular stimulation (GVS) causes a lateral body sway toward the anode. Previously, we have shown that this new position is actively stabilized, suggesting that GVS changes a set point in the reflex mechanisms controlling body posture. The aim of the present study was to reveal the underlying neuronal mechanisms. Experiments were performed on decerebrate rabbits. The vertebral column was rigidly fixed, whereas hindlimbs were positioned on a platform. Periodic lateral tilts of the platform caused postural limb reflexes (PLRs): activation of extensors in the loaded and flexing limb and a decrease in extensor activity in the opposite (unloaded and extending) limb. Putative spinal interneurons were recorded in segments L4-L5 during PLRs, with and without GVS. We have found that GVS enhanced PLRs on the cathode side and reduced them on the anode side. This asymmetry in PLRs can account for changes in the stabilized body orientation observed in normal rabbits subjected to continuous GVS. Responses to platform tilts (frequency modulation) were observed in 106 spinal neurons, suggesting that they can contribute to PLR generation. Two neuron groups were active in opposite phases of the tilt cycle of the ipsi-limb: F-neurons in the flexion phase, and E-neurons in the extension phase. Neurons were driven mainly by afferent input from the ipsi-limb. If one supposes that F- and E-neurons contribute, respectively, to excitation and inhibition of extensor motoneurons, one can expect that the pattern of response to GVS in F-neurons will be similar to that in extensor muscles, whereas E-neurons will have an opposite pattern. We have found that ~40% of all modulated neurons meet this condition, suggesting that they contribute to the generation of PLRs and to the GVS-caused changes in PLRs.

Altered muscular activation patterns and force feedback after spinal cord injury

One of the major clinical problems associated with spinal cord injury (SCI) is the lack of animal's ability to maintain weight support during standing or walking. We hypothesize that following SCI there is reorganization of the postural limb reflexes driven by stretch and load receptors in addition to loss of excitatory inputs from supraspinal structures to spinal interneurons that could result in altered intermuscular interactions. In control decerebrate animals there is a proximal to distal gradient in the strength of inhibitory force feedback among the limb muscles. We propose that pathways mediating this inhibition may remain inhibitory after spinal hemisection but their strengths may change to a distal to proximal gradient in the animal resulting in a loss of weight support. We also propose that ventral horn pathways are important for regulating the distribution of intermuscular force feedback. To test our hypothesis we are studying two types of SCI, namely dorsal and lateral hemisections, at both acute and chronic time points post‐injury. We measured intermuscular force feedback using combinations of stretches applied to pairs of muscles. Our most recent evidence supports our hypothesis and shows that the intermuscular force feedback is reversed after lateral but not dorsal hemisections.This work is supported by NIH grant HD32571, 1 I01 RX000243‐01A1, State of Florida BSCIRTF

Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia- reperfusion injury.

Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

Plantar cutaneous sensitivity as a risk for falls in the elderly

The risk factors for falls in the elderly are many and may be due to syncope and pre-syncope caused by cardiovascular diseases; neurological diseases, such as epilepsy and Parkinson’s disease; dementia disorders; and dependence in activities of daily life 1 . Other risk factors that also cause syncope and fall include the adverse effect or inappropriate use of several concurrent medications, drugs which are central nervous system-depressant, or act on the cardiocirculatory system 1 . Systemic diseases combined with sensorineural degeneration and neuromuscular disorders due to aging accentuate the risk of falling, particularly in the frail elderly. Vertigo and imbalance are also frequent causes of falls, often associated with metabolic disorders, mainly uncontrolled diabetes without the well-known clinical manifestations of the disease 2,3 . Diabetes leads to glucose fluctuations in metabolically active structures of the inner ear, interfering with the sodiumpotassium pump activity. This pump creates the electrical potentials of the cochlear and vestibular neuroepithelial cells that, when altered, produce auditory and vestibular signs and symptoms. Among the causes of change in body balance there are also the reduced number of mechanoreceptors located in the feet, and the increase in the vibrational excitation threshold of the plantar cutaneous mechanoreceptors due to aging. Plantar sensitivity is an important source of information for balance control, as it codifies the changes in pressure under the feet, especially during gait. This information reaches the brain, which senses the body position and, if necessary, generates postural reflexes to maintain an upright position 4 . This sensitivity loss may be due to several diseases, particularly diabetes 5 . About 50% of diabetic patients over 60 years of age have this disorder, with or without complaint. Moreover, even the healthy elderly may have subclinical neuropathy. It has been widely demonstrated that this loss plays an important role in balance disorders in the elderly population 4-6 . Change in plantar cutaneous sensitivity is an independent predictor of falls; 30% of the elderly people aged 65, and 40% of those aged 75 and over have fallen at least once 7 . Two or more falls in six months significantly increases the risk of falls in the frail elderly. Quality of life is compromised by a sense of instability that causes fear of falling, especially if the elder has fallen recently 7 . Fear of falling leads to reduced mobility, increasing sedentary lifestyle and creating a vicious cycle that further increases the risk 7,8 . Frequent falls often

Abstract 2675: Acute Curcumin Treatment Reduces Cerebrovascular Injury and Neurological Deficit in Stroked Type 2 Diabetic Rats

Background: Curcumin, a derivative of the rhizome Curcuma longa , has antioxidant, anti-inflammatory, and anti-apoptotic properties that make it an attractive potential threrapeutic agent for acute ischemic stroke. Studies using curcumin have shown that it provides neuroprotection when administered prior to focal cerebral ischemia or within 30 min to 1h after middle cerebral artery occlusion (MCAO) in normoglycemic animals. We previously reported that 3 h MCAO followed by 21 h reperfusion induces greater edema, hemorrhage, and neurological deficits in type 2 diabetic rats when compared to normoglycemic controls. Therefore, the goal of this study was to test the hypothesis that curcumin, when administered at recanalization, will decrease neurovascular injury, incidence of bleeding, and improve functional outcome in diabetic rats. Methods: Focal ischemia was induced by 3 h MCAO and 21 h reperfusion in sham, untreated, and curcumin-treated groups (n=5-7 per group). A single dose of curcumin (250 mg/kg, i.p.) or vehicle (EtOH + ethyl oleate) was administered at recanalization in control or diabetic (Goto-Kakizaki) rats. Percent (%) infarct, edema ratio (edema/infarct), and incidence of macroscopic bleeding was assessed in all groups. Neurological tests were performed at baseline and 23 h after MCAO to assess locomotor ability (beam walk), grip strength, and the presence or absence of postural reflexes (circling, resistance to push, forearm flexion, and hindlimb extension). Results: Within the untreated groups, % infarct was greater in controls (57.7±5.8% vs. 9.1±1.0%), while edema ratio was greater in diabetic animals (1.8±0.2 vs. 0.2±0.03). Bleeding was present in the ischemic hemispheres of all diabetic rats and in 43% of the controls. Compared to controls, neurological deficits were greater in diabetic animals after focal ischemia (p<0.05). Curcumin reduced % infarct in controls (30.0±9.9% vs. 9.8±1.8%) and improved edema ratio in diabetic rats (0.7±0.05 vs. 0.2±0.04). Curcumin also reduced the incidence of bleeding in both control and diabetic animals (20% vs. 50%). Incidence of pathological postural reflexes in both control and diabetic animals was decreased following curcumin treatment however it did not improve beam walk scores or grip strength in either group (p<0.05). Vehicle-treated animals were similar to untreated controls at all endpoints. Conclusion: Curcumin provides protection against infarct in normoglycemic animals and vascular protection in diabetic animals when administered at recanalization, suggesting that its use as a therapeutic agent at this clinically relevant time point may be beneficial in both groups but through different mechanisms. Additional long-term studies are needed to determine whether acute curcumin treatment at recanalization is sufficient to improve locomotor ability and grip strength deficits beyond 24 h post-MCAO.

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

Mild therapeutic hypothermia (HT) reduces brain injury in survivors after perinatal asphyxia. Recent guidelines suggest that resuscitation of term infants should be started with air, but supplemental oxygen is still in use. It is not known whether supplemental oxygen during resuscitation affects the protection offered by subsequent HT. Wilcoxon median (95% confidence interval) hippocampal injury scores (range 0.0-4.0; 0 to ≥90% injury) were 21% O(2) normothermia (NT): 2.00 (1.25-2.50), 21% O(2) HT: 1.00 (0.50-1.50), 100% O(2) NT: 2.50 (1.50-3.25), and 100% O(2) HT: 2.00 (1.25-2.50). Although HT significantly reduced hippocampal injury (B = -0.721, SEM = 0.297, P = 0.018), reoxygenation with 100% O(2) increased injury (B = +0.647, SEM = 0.297, P = 0.033). Regression constant B = 1.896, SEM = 0.257 and normally distributed residuals. We confirm an ~50% neuroprotective effect of therapeutic HT in the neonatal rat. Reoxygenation with 100% O(2) increased injury and worsened reflex performance. HT was neuroprotective whether applied after reoxygenation with air or 100% O(2). However, HT after 100% O(2) gave no net neuroprotection. In an established neonatal rat model, hypoxia-ischemia (HI) was followed by 30-min reoxygenation in either 21% O(2) or 100% O(2) before 5 h of NT (37 °C) or HT (32 °C). The effects of HT and 100% O(2) on histopathologic injury in the hippocampus, basal ganglia, and cortex, and on postural reflex performance 7 d after the insult, were estimated by linear regression.

A Promoter Polymorphism of Neurotrophin 3 Gene Is Associated With Curve Severity and Bracing Effectiveness in Adolescent Idiopathic Scoliosis

A genetic association study to comprehensively investigate variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han population. To explore whether the NTF3 gene polymorphisms are associated with the susceptibility, curve severity, or bracing effectiveness of adolescent idiopathic scoliosis (AIS). Scoliosis has developed in mice with NTF3 deficiency in previous studies. Increased expression of NTF3 mRNA was detected in the paravertebral muscle in AIS. Moreover, linkage study has defined a novel AIS locus on chromosome 12p while NTF3 gene is located exactly in this interval. All evidence indicates a potential role of NTF3 in the pathogenesis of AIS. As for brace treatment of AIS, continuous sensory stimulation caused by an orthosis could help awareness of body misalignment and trigger curve correction through postural reflex. While NTF3 gene is tightly associated with proprioceptive feedback mechanism to adjust postural control, we hypothesized NTF3 as a potential candidate gene associated with the bracing effectiveness. A total of 362 AIS patients and 377 age-matched healthy controls were recruited. Two single-nucleotide polymorphisms (SNPs) were selected on the basis of the Chinese data from the HapMap project, and genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism for each SNP, respectively. Case-control study and case-only study were performed to define the contribution of NTF3 gene polymorphisms to predisposition and disease severity of AIS. Another subgroup of 120 skeletally immature AIS patients who received continuous brace treatment for minimal 2 years was genotyped, and bracing effectiveness was assessed to determine its association with NTF3 gene polymorphisms. The genotype and allele frequency distribution were similar between AIS and normal control for these 2 SNPs (χ² test: P > 0.05). For SNP rs11063714 in the promoter region of NTF3 gene, AIS patients with AA genotype showed significantly lower mean maximum Cobb angle than the patients with AG or GG genotypes (analysis of variance: P = 0.008). In addition, skeletally immature bracing AIS patients with AA genotype possessed significantly higher successful ratio of brace treatment compared with GG genotype (χ² test: P = 0.043). For SNP rs1805149, no significant association with predisposition or curve severity was detected. The NTF3 gene polymorphisms are not associated with the occurrence of AIS, but the promoter polymorphism (rs11063714) is associated with the curve severity, implicating an alleviating role of NTF3 in the curve progression of AIS. In addition, the promoter polymorphism is also associated with brace responsiveness. These findings indicated that NTF3 gene might be a disease-modifying gene of AIS.

Magnetic resonance imaging in pantothenate kinase-2-associated neurodegeneration

Pantothenate kinase-2-associated neurodegeneration (PKAN) is a rare autosomal recessive pediatric neurodegenerative disorder characterized by rigidity, dystonia, impaired postural reflexes, and progressive dementia. On T2-weighted magnetic resonance imaging images, marked low signal intensity is seen in the globus pallidus. This low signal intensity surrounds a central region of high signal intensity in the anteromedial globus pallidus, giving an eye-of-the-tiger appearance.

Effect of Dietary <i>Kaempferia parviflora</i> on Ischemic Brain Injury in the rat

Problem statement: Stroke often causes irreversible neuronal damage and related behavioral deficits. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional plant medicines. We investigated the ability of consuming Kaempferia parviflora extract, a Thai medicinal plant reputed for neuroprotective effects against brain damage, reduced infarct volume and improve neurological outcome in rats with permanent right Middle Cerebral Artery Occlusion (MCAO). Approach: Male adult Wistar rats were administrated an alcoholic extract of KP orally once daily at a period of 14 days before and 7 days after MCAO. Neurological function assessment was performed at 7 days after MCAO using the 6-points postural reflex test. The brain infarct volume and the densities of survival neurons in hippocampus were also determined at the end of experiment. Results: Oral administration with KP at a dose of 200 mg kg-1 BW significantly improved the neurological behavior performances and reduced the infarct volume when compared to the vehicle treated group. The reductions of survival neurons densities were also mitigated. Conclusion: The consumption of KP extract may have the possibility of protective effect against neurological disorders such as brain ischemia, while further investigations about precise underlying the defense mechanism against cerebral ischemia are still required.

What Does Galvanic Vestibular Stimulation Actually Activate?

What Does Galvanic Vestibular Stimulation Actually Activate?

The Frog Vestibular System as a Model for Lesion-Induced Plasticity: Basic Neural Principles and Implications for Posture Control

Studies of behavioral consequences after unilateral labyrinthectomy have a long tradition in the quest of determining rules and limitations of the central nervous system (CNS) to exert plastic changes that assist the recuperation from the loss of sensory inputs. Frogs were among the first animal models to illustrate general principles of regenerative capacity and reorganizational neural flexibility after a vestibular lesion. The continuous successful use of the latter animals is in part based on the easy access and identifiability of nerve branches to inner ear organs for surgical intervention, the possibility to employ whole brain preparations for in vitro studies and the limited degree of freedom of postural reflexes for quantification of behavioral impairments and subsequent improvements. Major discoveries that increased the knowledge of post-lesional reactive mechanisms in the CNS include alterations in vestibular commissural signal processing and activation of cooperative changes in excitatory and inhibitory inputs to disfacilitated neurons. Moreover, the observed increase of synaptic efficacy in propriospinal circuits illustrates the importance of limb proprioceptive inputs for postural recovery. Accumulated evidence suggests that the lesion-induced neural plasticity is not a goal-directed process that aims toward a meaningful restoration of vestibular reflexes but rather attempts a survival of those neurons that have lost their excitatory inputs. Accordingly, the reaction mechanism causes an improvement of some components but also a deterioration of other aspects as seen by spatio-temporally inappropriate vestibulo-motor responses, similar to the consequences of plasticity processes in various sensory systems and species. The generality of the findings indicate that frogs continue to form a highly amenable vertebrate model system for exploring molecular and physiological events during cellular and network reorganization after a loss of vestibular function.

Artificial balancer – Supporting device for postural reflex

The evolutionarily novel ability to keep ones body upright while standing or walking, the human balance, deteriorates in old age or can be compromised after accidents or brain surgeries. With the aged society, age related balance problems are on the rise. Persons with balance problems are more likely to fall during their everyday life routines. Especially in elderly, falls can lead to bone fractures making the patient bedridden, weakening the body and making it more prone to other diseases. Health care expenses for a fall patient are often very high. There is a great deal of research being done on exoskeletons and power assists. However, these technologies concentrate mainly on the amplifications of human muscle power while balance has to be provided by the human themself.Our research has been focused on supporting human balance in harmony with the human's own posture control mechanisms such as postural reflexes. This paper proposes an artificial balancer that supports human balance through acceleration of a flywheel attached to the body. Appropriate correcting torques are generated through our device based on the measurements of body deflections. We have carried out experiments with test persons standing on a platform subject to lateral perturbations and ambulatory experiments while walking on a balance beam. These experiments have demonstrated the effectiveness of our device in supporting balance and the possibility of enhancing balance-keeping capability in human beings through the application of external torque.

Parkinsonism: heterogeneity of a common neurological syndrome

Parkinsonism refers to a neurological syndrome embracing bradykinesia, muscle rigidity, tremor at rest and impaired postural reflexes, and involving a broad differential diagnosis. Having ruled out secondary causes (most importantly drugs), distinguishing levodopa-responsive idiopathic parkinson's disease (PD) from chiefly treatment-resistant and hence atypical parkinsonism is essential. Recent clinico-pathological studies using data-driven approaches have refined the traditional classifications of parkinsonism by identifying a spectrum of subtypes with different prognoses. For example, progressive supranuclear palsy (PSP), characterised by early vertical gaze limitation and falls, probably has a milder variant with predominant parkinsonism (PSP-P) which may respond quite well to levodopa before converting to the classical disease, relabelled Richardson syndrome (PSP-RS). Analysis of PD subcategories has shown that tremor-dominant forms are probably less benign than was hitherto thought and that in mild cases dystonia should rather be considered. In addition, life expectancy in early onset PD may be shortened. Despite the clinical and pathological overlap of the various subtypes, appreciating the heterogeneity of parkinsonism also includes identifying non-motor features such as early autonomous or cognitive problems which are potentially amenable to pharmacological treatment. Not least, non-motor symptoms, along with postural instability, render the patient particularly vulnerable to side effects, and hence avoiding unnecessary treatment is equally important in the management of parkinsonian disorders.

A Classification of Postural Sway Patterns During Upright Stance in Healthy Adults and Patients with Parkinson’s Disease

The intermittent control during human quiet upright stance is a new hypothesis which claims that the active neural feedback control generating the ankle muscle torque is switched off and on intermittently at appropriate timings. The intermittent strategy is capable of providing compliant posture while ensuring robust stability. Contrastingly, impairment of postural reflexes in patients with Parkinson’s disease (PD) causes postural instability. Here we hypothesize that the instability in PD patients might be due to a loss of appropriate intermittent activations in the feedback muscle torque during stance. In order to provide evidence for this hypothesis, we characterized stochastic postural sway patterns measured as changes in center of pressure (CoP) and activities of ankle muscles during quiet stance in healthy young and elderly subjects as well as PD patients. To this end, sway patterns and associated ankle muscle activities were quantified by several indices including the CoP sway area, scaling factors of double-power-law power spectra of the sway, as well as levels and patterns of the muscle activations. Hierarchical cluster analysis was performed to suggest that the sway patterns could be classified into two major types. The first type consisted mainly of sway and muscle activation patterns from healthy subjects and some PD patients with the mild level of severity, and they showed features indicating the intermittent control. The second type, consisting mainly of PD patients with relatively severe levels of motor symptoms, was accompanied with non-intermittent but tonic muscle activities and sway areas either smaller or larger than those in the first type. Moreover, the major two types were further classified into several subtypes with distinguishable characteristics. Results suggested that a loss of the intermittent activations in the ankle muscles could be a cause of the postural instability for a population of PD patients.

Vestibular information is necessary for maintaining metric properties of representational space: Evidence from mental imagery

The vestibular system contributes to a wide range of functions, from postural and oculomotor reflexes to spatial representation and cognition. Vestibular signals are important to maintain an internal, updated representation of the body position and movement in space. However, it is not clear to what extent they are also necessary to mentally simulate movement in situations that do not involve displacements of the body, as in mental imagery. The present study assessed how vestibular loss can affect object-based mental transformations (OMTs), i.e., imagined rotations or translations of objects relative to the environment. Participants performed one task of mental rotation of 3D-objects and two mental scanning tasks dealing with the ability to build and manipulate mental images that have metric properties. Menière's disease patients were tested before unilateral vestibular neurotomy and during the recovery period (1 week and 1 month). They were compared to healthy participants tested at similar time intervals and to bilateral vestibular-defective patients tested after the recovery period. Vestibular loss impaired all mental imagery tasks. Performance varied according to the extent of vestibular loss (bilateral patients were frequently the most impaired) and according to the time elapsed after unilateral vestibular neurotomy (deficits were stronger at the early stage after neurotomy and then gradually compensated). These findings indicate that vestibular signals are necessary to perform OMTs and provide the first demonstration of the critical role of vestibular signals in processing metric properties of mental representations. They suggest that vestibular loss disorganizes brain structures commonly involved in mental imagery, and more generally in mental representation.

Sensorimotor performance deficits induced by chronic chlorpyrifos exposure in Wistar rats: mitigative effect of vitamin C

This study was aimed at evaluating the ameliorative effect of vitamin C on chlorpyrifos-induced sensorimotor changes involving postural reflex, limb placing, and vibrissae touch in Wistar rats. Forty adult Wistar rats of either sex were divided into 4 groups of 10 animals in each group. Group I was administered soya oil (2 mL kg−1) while group II was given vitamin C (100 mg kg−1); group III was dosed with chlorpyrifos (10.6 mg kg−1, i.e. ∼1/8th of the LD50); group IV was administered vitamin C (100 mg kg−1) and then exposed to chlorpyrifos (10.6 mg kg−1), 30 min later. The regimens were administered by gavage once daily for a period of 17 weeks. Neurobehavioral parameters involving postural reflex, limb placing, and vibrissae touch responses measured at various intervals revealed a deficit in postural reflex, limb placing, and vibrissae touch responses in the CPF group, which was mitigated by vitamin C pretreatment. The neuronal and glial cell degeneration, increased brain malonaldehyde concentration, and decrease in superoxide dismutase, catalase, and acetylcholinesterase activities recorded in the group given chlorpyrifos were ameliorated by vitamin C. Therefore, vitamin C was shown to mitigate chlorpyrifos-induced sensorimotor deficits partly due to its antioxidant and acetylcholinesterase restoration properties.

Aripiprazole-Induced Parkinsonism in a Child

To the Editor: Parkinsonism is a neurologic syndrome that manifests as any combination of 6 cardinal features: tremor at rest, rigidity, bradykinesia/hypokinesia, flexed posture, loss of postural reflexes, and the freezing phenomenon.1 At least 2 of these features, with at least 1 being either tremor at rest or bradykinesia, must be present for a definitive diagnosis of parkinsonism.1 The biochemical abnormality in parkinsonism is reduced dopaminergic neurotransmission in the basal ganglia.1 In 1954, Steck2 first described neuroleptic-induced parkinsonism in patients taking chlorpromazine. This observation was confirmed by Gade and Heinrich3 in 1955. The prevalence of neuroleptic-induced parkinsonism is difficult to ascertain because of heterogenous patient populations, variable drug regimens, and other factors that make this distinction extremely difficult. In most cases, however, it is second only to Parkinson's disease as the most common cause of parkinsonism.4,5,6 Various medications such as neuroleptics, selective serotonin reuptake inhibitors, lithium, valproic acid, calcium channel blockers, antiarrhythmics, procholinergics, chemotherapeutics, amphotericin B, estrogen, and others have been implicated.4 To our knowledge, we are reporting the first published case of aripiprazole-induced parkinsonism. Case report. A 12-year-old white boy presented to the emergency department in 2010 with chief complaints of excessive drooling, generalized slowing of body movements, and difficulty in walking with stiffness in arms and legs for 3 days. His psychiatric history was significant for posttraumatic stress disorder (PTSD; nightmares, flashbacks, numbing, avoidance, and sexually acting-out behavior) due to physical and sexual abuse, attention-deficit/hyperactivity disorder (ADHD; hyperactivity, impulsivity, and inattention), oppositional defiant disorder (ODD), and mood disorder not otherwise specified (longstanding history of mood dysregulation, mood swings, and excessive irritability). On mental status examination, he described his mood as “sad.” His affect was blunted, his speech was limited to short response, and he denied having audiovisual hallucinations. He was not delirious. On physical examination, he was found to have bradykinesia, lip smacking, flexed posture, and cogwheel rigidity. There was no past history of illicit substance or alcohol abuse. There was no family history of movement disorders. His outpatient medications included lisdexamfetamine 70 mg orally every morning and guanfacine 1 mg orally every morning. Within 3 days of initiation of benztropine 1 mg orally twice daily and aripiprazole 5 mg/d orally, he developed classic parkinsonian symptoms, ie, bradykinesia, cogwheel rigidity, and flexed posture. After emergency department stabilization, he was admitted to the inpatient psychiatry unit with an additional diagnosis of neuroleptic-induced parkinsonism. Findings from his routine blood work including complete blood cell count with differential, comprehensive metabolic profile, and drug screen as well as noncontrast head computed tomography scan were within normal limits. All medications were stopped except benztropine 1 mg orally twice daily, and amantadine 100 mg orally twice daily was given, which led to symptom resolution within 72 hours. After release from the hospital, he was rechallenged with an antipsychotic, quetiapine extended release (XR) 50 mg orally every evening, with reemergence of parkinsonian symptoms. Quetiapine XR was discontinued, with dramatic resolution of parkinsonian symptoms. A PubMed search for the years 1954 to 2010 with the keywords antipsychotics, aripiprazole, parkinsonism, and children was performed, and a Google Scholar search incorporating the same keywords and range of years was also conducted. To our knowledge, only 2 casereports of drug-induced parkinsonism in children7,8 have been published. Neuroleptic-induced parkinsonism results from a diminution in dopamine activity.9 This can be induced by depletion of dopamine in presynaptic stores (eg, during reserpine treatment), dopamine-blocking agents (eg, antipsychotics), and the atypical calcium-blocking agent cinnarizine.9 Dopamine-2 blockade in nigrostriatal dopamine system results in parkinsonian symptoms in patients who are taking antipsychotics.10 This effect is frequent with typical antipsychotics, being strong D2 blockers, compared to atypical antipsychotics, which are relatively weak D2 blockers.11 Absence of tremor and reversibility are typical of drug-induced parkinsonism rather than Parkinson's disease.12 This syndrome usually subsides with dose reduction or medication cessation.9 As such reduction or cessation is not always possible, alternative strategies include switching from a high-potency D2 blocking agent (eg, fluphenazine) to a lower-potency first-generation antipsychotic or second-generation antipsychotic agent (eg, quetiapine). According to the literature, aripiprazole, a partial D2 agonist, may also decrease the risk of acute extrapyramidal symptoms.9 Adjunctive anticholinergic agents, eg, benztropine or dopamine agonists such as amantadine, are effective agents to alleviate extrapyramidal symptoms (EPS).9 Physicians should look for the symptoms of parkinsonism and movement disorders in children who are on treatment with antipsychotics, either typical or atypical. Incidence of EPS appears to be greater for typical antipsychotics. Among atypical antipsychotics, hierarchy of EPS risk is risperidone > olanzapine = ziprasidone = aripiprazole > quetiapine > clozapine.10,13 If challenged by a neuroleptic again, patients may have reemergence of parkinsonian symptoms.

Facilitation of postural limb reflexes in spinal rabbits by serotonergic agonist administration, epidural electrical stimulation, and postural training

In quadrupeds, spinalization in the thoracic region severely impairs postural control in the hindquarters. The goal of this study was to improve postural functions in chronic spinal rabbits by regular application of different factors: intrathecal injection of the 5-HT(2) agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), epidural electrical spinal cord stimulation (EES), and specific postural training (SPT). The factors were used either alone (SPT group) or in combination (DOI+SPT, EES+SPT, and DOI+EES+SPT groups) or not used (control group). It was found that in none of these groups did normal postural corrective movements in response to lateral tilts of the supporting platform reappear within the month of treatment. In control group, reduced irregular electromyographic (EMG) responses, either correctly or incorrectly phased in relation to tilts, were observed. By contrast, in DOI+SPT and EES+SPT groups, a gradual threefold increase in the proportion of correctly phased EMG responses (compared with control) was observed. The increase was smaller in DOI+EES+SPT and SPT groups. Dissimilarly to these long-term effects, short-term effects of DOI and EES were weak or absent. In addition, gradual development of oscillatory EMG activity in the responses to tilts, characteristic for the control group, was retarded in DOI+SPT, EES+SPT, DOI+EES+SPT, and SPT groups. Thus regular application of the three tested factors and their combinations caused progressive, long-lasting plastic changes in the isolated spinal networks, resulting in the facilitation of spinal postural reflexes and in the retardation of the development of oscillatory EMG activity. The facilitated reflexes, however, were insufficient for normal postural functions.

Gait disturbances in Parkinson disease. Did freezing of gait exist before levodopa? Historical review

Gait disturbances occur frequently in advanced Parkinson's disease (PD) including slow gait, postural changes, festination and freezing of gait. We have reviewed descriptions of gait abnormalities in PD from classic predopa-literature and compared them with those found in contemporary references.Several components of gait disturbances associated with shaking palsy were very well known in classic literature. James Parkinson, Charcot, Gowers and Wilson described slowness of gait, postural changes, loss of postural reflexes and festination; according to James Parkinson, festination was a pathognomonic element in shaking palsy. In contrast, freezing of gait was rarely mentioned in historic literature save for anecdotal reports (Buzzard 1888). Freezing of gait was fully noticed after the chronic use of levodopa (Barbeau and Ambani).In this historical review, we analyze the concept, identification and evolution of gait disturbances in PD through the time.

Can imagined whole-body rotations improve vestibular compensation?

Unilateral damage to the labyrinth and the vestibular nerve cause rotational vertigo, postural imbalance, oculomotor disorders and spatial disorientation. Electrophysiological investigations in animals revealed that such deficits are partly due to imbalanced spontaneous activity and sensitivity to motion in neurons located in the ipsilesional and contralesional vestibular nuclei. Neurophysiological reorganizations taking place in the vestibular nuclei are the basis of the decline of the symptoms over time, a phenomenon known as vestibular compensation. Vestibular compensation is facilitated by motor activity and sensory experience, and current rehabilitation programs favor physical activity during the acute stage of a unilateral vestibular loss. Unfortunately, vestibular-defective patients tend to develop strategies in order to avoid movements causing imbalance and nausea (in particular body movements towards the lesioned side), which impedes vestibular compensation. Neuroanatomical evidence suggests a cortical control of postural and oculomotor reflexes based on corticofugal projections to the vestibular nuclei and, therefore, the possibility to manipulate vestibular functions through top-down mechanisms. Based on evidence from neuroimaging studies showing that imagined whole-body movements can activate part of the vestibular cortex, we propose that mental imagery of whole-body rotations to the lesioned and to the healthy side will help rebalancing the activity in the ipsilesional and contralesional vestibular nuclei. Whether imagined whole-body rotations can improve vestibular compensation could be tested in a randomized controlled study in such patients beneficiating, or not, from a mental imagery training. If validated, this hypothesis will help developing a method contributing to reduce postural instability and falls in vestibular-defective patients. Imagined whole-body rotations thus could provide a simple, safe, home-based and self-administered therapeutic method with the potential to overcome the inconvenience related to physical movements.