The Theory and Neuroscience of Cerebellar Cognition.

Cerebellar neuroscience has undergone a paradigm shift. The theories of the universal cerebellar transform and dysmetria of thought and the principles of organization of cerebral cortical connections, together with neuroanatomical, brain imaging, and clinical observations, have recontextualized the cerebellum as a critical node in the distributed neural circuits subserving behavior. The framework for cerebellar cognition stems from the identification of three cognitive representations in the posterior lobe, which are interconnected with cerebral association areas and distinct from the primary and secondary cerebellar sensorimotor representations linked with the spinal cord and cerebral motor areas. Lesions of the anterior lobe primary sensorimotor representations produce dysmetria of movement, the cerebellar motor syndrome. Lesions of the posterior lobe cognitive-emotional cerebellum produce dysmetria of thought and emotion, the cerebellar cognitive affective/Schmahmann syndrome. The notion that the cerebellum modulates thought and emotion in the same way that it modulates motor control advances the understanding of the mechanisms of cognition and opens new therapeutic opportunities in behavioral neurology and neuropsychiatry.

Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity.

Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have greater force dysmetria but display better temporal accuracy during fast goal directed contractions. Here, we test whether greater temporal accuracy occurs in all individuals with SCA6, and can be explained by lesser temporal variability. Further we examine whether it is linked to disease severity and specific degenerative changes in the cerebellum. Nineteen human participants with SCA6 (13 woman) and 18 healthy controls performed fast goal-directed ankle dorsiflexion contractions aiming at a spatiotemporal target. We quantified the endpoint control of these contractions, gray matter (GM) integrity of the cerebellum, and disease severity using the International Cooperative Ataxia Rating Scale (ICARS). SCA6 individuals exhibited lower temporal endpoint error and variability than the healthy controls (p = 0.008). Statistically, SCA6 clustered into two distinct groups for temporal variability. A group with low temporal variability ranging from 10 to 19% (SCA6a) and a group with temporal variability similar to healthy controls (SCA6b; 19-40%).SCA6a exhibited greater disease severity than SCA6b, as assessed with ICARS (p < 0.001). Lower temporal variability, which was not associated with disease duration (R2 = 0.1, p > 0.2), did correlate with both greater ICARS (R2 = 0.3) and reduced GM volume in cerebellar lobule VI (R2 = 0.35). Other cerebellar lobules did not relate to temporal variability. We provide new evidence that a subset of SCA6 with greater loss of GM in cerebellum lobule VI exhibit temporal invariance and more severe ataxia than other SCA6 individuals.SIGNIFICANCE STATEMENT Variability is an inherent feature of voluntary movement, and traditionally more variability in the targeted output infers impaired performance. For example, cerebellar patients present exacerbated temporal variability during multijoint movements, which is thought to contribute to their motor deficits. In the current work, we show that in a subgroup of spinocerebellar ataxia type 6 individuals, temporal variability is lower than that of healthy controls when performing single-joint fast-goal directed movements. This invariance related to exacerbated atrophy of lobule VI of the cerebellum and exacerbated disease severity. The relation between invariance and disease severity suggests that pathological motor variability can manifest not only as an exacerbation but also as a reduction relative to healthy controls.

Temporal but not spatial dysmetria relates to disease severity in FA.

Friedreich's ataxia (FA) is an inherited disease that causes degeneration of the nervous system. Features of FA include proprioceptive and cerebellar deficits leading to impaired muscle coordination and, consequently, dysmetria in force and time of movement. The aim of this study is to characterize dysmetria and its association to disease severity. Also, we examine the neural mechanisms of dysmetria by quantifying the EMG burst area, duration, and time-to-peak of the agonist muscle. Twenty-seven individuals with FA and 13 healthy controls (HCs) performed the modified Functional Ataxia Rating Scale and goal-directed movements with the ankle. Dysmetria was quantified as position and time error during dorsiflexion. FA individuals exhibited greater time but not position error than HCs. Moreover, time error correlated with disease severity and was related to increased agonist EMG burst. Temporal dysmetria is associated to disease severity, likely due to altered activation of the agonist muscle.NEW & NOTEWORTHY For the first time, we quantified spatial and temporal dysmetria and its relation to disease severity in Friedreich's ataxia (FA). We found that FA individuals exhibit temporal but not spatial dysmetria relative to healthy controls. Temporal dysmetria correlated to disease severity in FA and was predicted from an altered activation of the agonist muscle. Therefore, these results provide novel evidence that FA exhibit temporal but not spatial dysmetria, which is different from previous findings on SCA6.

Dysmetria and Errors in Predictions: The Role of Internal Forward Model.

The terminology of cerebellar dysmetria embraces a ubiquitous symptom in motor deficits, oculomotor symptoms, and cognitive/emotional symptoms occurring in cerebellar ataxias. Patients with episodic ataxia exhibit recurrent episodes of ataxia, including motor dysmetria. Despite the consensus that cerebellar dysmetria is a cardinal symptom, there is still no agreement on its pathophysiological mechanisms to date since its first clinical description by Babinski. We argue that impairment in the predictive computation for voluntary movements explains a range of characteristics accompanied by dysmetria. Within this framework, the cerebellum acquires and maintains an internal forward model, which predicts current and future states of the body by integrating an estimate of the previous state and a given efference copy of motor commands. Two of our recent studies experimentally support the internal-forward-model hypothesis of the cerebellar circuitry. First, the cerebellar outputs (firing rates of dentate nucleus cells) contain predictive information for the future cerebellar inputs (firing rates of mossy fibers). Second, a component of movement kinematics is predictive for target motions in control subjects. In cerebellar patients, the predictive component lags behind a target motion and is compensated with a feedback component. Furthermore, a clinical analysis has examined kinematic and electromyography (EMG) features using a task of elbow flexion goal-directed movements, which mimics the finger-to-nose test. Consistent with the hypothesis of the internal forward model, the predictive activations in the triceps muscles are impaired, and the impaired predictive activations result in hypermetria (overshoot). Dysmetria stems from deficits in the predictive computation of the internal forward model in the cerebellum. Errors in this fundamental mechanism result in undershoot (hypometria) and overshoot during voluntary motor actions. The predictive computation of the forward model affords error-based motor learning, coordination of multiple degrees of freedom, and adequate timing of muscle activities. Both the timing and synergy theory fit with the internal forward model, microzones being the elemental computational unit, and the anatomical organization of converging inputs to the Purkinje neurons providing them the unique property of a perceptron in the brain. We propose that motor dysmetria observed in attacks of ataxia occurs as a result of impaired predictive computation of the internal forward model in the cerebellum.

Impaired Motor Learning in a Disorder of the Inferior Olive: Is the Cerebellum Confused?

An attractive hypothesis about how the brain learns to keep its motor commands accurate is centered on the idea that the cerebellar cortex associates error signals carried by climbing fibers with simultaneous activity in parallel fibers. Motor learning can be impaired if the error signals are not transmitted, are incorrect, or are misinterpreted by the cerebellar cortex. Learning might also be impaired if the brain is overwhelmed with a sustained barrage of meaningless information unrelated to simultaneously appearing error signals about incorrect performance. We test this concept in subjects with syndrome of oculopalatal tremor (OPT), a rare disease with spontaneous, irregular, roughly pendular oscillations of the eyes thought to reflect an abnormal, synchronous, spontaneous discharge to the cerebellum from the degenerating neurons in the inferior olive. We examined motor learning during a short-term, saccade adaptation paradigm in patients with OPT and found a unique pattern of disturbed adaptation, quite different from the abnormal adaption when the cerebellum is involved directly. Both fast (seconds) and slow (minutes) timescales of learning were impaired. We suggest that the spontaneous, continuous, synchronous output from the inferior olive prevents the cerebellum from receiving the error signals it needs for appropriate motor learning. The important message from this study is that impaired motor adaptation and resultant dysmetria is not the exclusive feature of cerebellar disorders, but it also highlights disorders of the inferior olive and its connections to the cerebellum.

Cerebellar Contribution to Social Cognition.

Emotion attribution (EA) from faces is key to social cognition, and deficits in perception of emotions from faces underlie neuropsychiatric disorders in which cerebellar pathology is reported. Here, we test the hypothesis that the cerebellum contributes to social cognition through EA from faces. We examined 57 patients with cerebellar disorders and 57 healthy controls. Thirty-one patients had complex cerebrocerebellar disease (complex cerebrocerebellar disease group (CD)); 26 had disease isolated to cerebellum (isolated cerebellar disease group (ID)). EA was measured with the Reading the Mind in the Eyes test (RMET), and informants were administered a novel questionnaire, the Cerebellar Neuropsychiatric Rating Scale (CNRS). EA was impaired in all patients (CD p < 0.001, ID p < 0.001). When analyzed for valence categories, both CD and ID missed more positive and negative stimuli. Positive targets produced the highest deficit (CD p < 0.001, ID p = 0.004). EA impairments correlated with CNRS measures of deficient social skills (p < 0.05) and autism spectrum behaviors (p < 0.005). Patients had difficulties with emotion regulation (CD p < 0.001, ID p < 0.001), autism spectrum behaviors (CD p < 0.049, ID p < 0.001), and psychosis spectrum symptoms (CD p < 0.021, ID p < 0.002). ID informants endorsed deficient social skills (CD p < 0.746, ID p < 0.003) and impaired attention regulation (CD p < 0.144, ID p < 0.001). Within the psychosis spectrum domain, CD patients were worse than controls for lack of empathy (CD p = 0.05; ID p = 0.49). Thus, patients with cerebellar damage were impaired on an EA task associated with deficient social skills and autism spectrum behaviors and experienced psychosocial difficulties on the CNRS. This has relevance for ataxias, the cerebellar cognitive affective/Schmahmann syndrome, and neuropsychiatric disorders with cerebellar pathology.

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

Predicting and correcting ataxia using a model of cerebellar function.

Cerebellar damage results in uncoordinated, variable and dysmetric movements known as ataxia. Here we show that we can reliably model single-joint reaching trajectories of patients (n = 10), reproduce patient-like deficits in the behaviour of controls (n = 11), and apply patient-specific compensations that improve reaching accuracy (P < 0.02). Our approach was motivated by the theory that the cerebellum is essential for updating and/or storing an internal dynamic model that relates motor commands to changes in body state (e.g. arm position and velocity). We hypothesized that cerebellar damage causes a mismatch between the brain's modelled dynamics and the actual body dynamics, resulting in ataxia. We used both behavioural and computational approaches to demonstrate that specific cerebellar patient deficits result from biased internal models. Our results strongly support the idea that an intact cerebellum is critical for maintaining accurate internal models of dynamics. Importantly, we demonstrate how subject-specific compensation can improve movement in cerebellar patients, who are notoriously unresponsive to treatment.

Psychiatric misdiagnoses in Dandy-Walker variant.

Cases of intellectual impairment and aberrant behavior in patients with cerebellar diseases have been described since the early nineteenth century. Here, we report on a patient suffering from Dandy-Walker variant who presented with symptoms of obsessive compulsive disorder and delusional disorder. The current findings emphasize the potential relevance of focal cerebellar lesions as organic correlates of these disorders.

Comprehensive Evaluation of Sporadic Late-Onset Cerebellar Ataxias: Clinical Presentation, Diagnostic Challenges, and Treatment Outcomes.

Sporadic late-onset cerebellar ataxias (SLOCA) present a diagnostic challenge due to their heterogeneous etiologies and complex clinical manifestations. This retrospective study aimed to conduct a comprehensive evaluation of six male patients diagnosed with SLOCA, with a mean age of 55 years and an average symptom onset at 47 years. All patients presented with gait and balance disturbances, with additional sensory abnormalities observed in two cases. Neurological examinations revealed varied cerebellar syndromes, including static and static-kinetic presentations, accompanied by peripheral neurogenic syndromes in some instances. Brain MRI findings showed cerebellar atrophy, predominantly involving the vermis, in a subset of patients. Biochemical and serological investigations yielded mostly unremarkable results, although two patients exhibited significant vitamin E deficiency and anti-Hu antibodies (anti-neuronal nuclear antibody type 1). Electromyography confirmed sensory axonal neuropathy in those with peripheral neurogenic syndromes. Treatment with TOCO 500 mg (Vitamin E) was administered to four patients, with follow-up indicating stable disease progression in two cases. This study underscores the complexity of SLOCA and the need for a multidisciplinary approach to diagnosis and management. Further research is warranted to elucidate the underlying mechanisms and improve clinical outcomes for affected individuals.

Virtual reality assessment of reaching accuracy in patients with recent cerebellar stroke.

Background: Dysmetria, the inability to accurately estimate distance in motor tasks, is a characteristic clinical feature of cerebellar injury. Even though subjective dysmetria can be quickly detected during the neurological examination with the finger-to-nose test, objective quantification of reaching accuracy for clinical assessment is still lacking. Emerging VR technology allows for the delivery of rich multisensory environmental stimuli with a high degree of control. Furthermore, recent improvements in the hand-tracking feature offer an opportunity to closely examine the speed, accuracy, and consistency of fine hand movements and proprioceptive function. This study aims to investigate the application of virtual reality (VR) with hand tracking in the rapid quantification of reaching accuracy at the bedside for patients with cerebellar stroke (CS). Methods and results: Thirty individuals (10 CS patients and 20 age-matched neurologically healthy controls) performed a simple task that allowed us to measure reaching accuracy using a VR headset (Oculus Quest 2). During this task, the participant was asked to reach for a target placed along a horizontal sixty-degree arc. Once the fingertip passed through the arc, the target immediately extinguished. 50% of the trials displayed a visible, real-time rendering of the hand as the participant reached for the target (visible hand condition), while the remaining 50% only showed the target being extinguished (invisible hand condition). The invisible hand condition isolates proprioception-guided movements by removing the visibility of the participant's hand. Reaching error was calculated as the difference in degrees between the location of the target, and where the fingertip contacted the arc. Both CS patients and age-matched controls displayed higher average reaching error and took longer to perform a reaching motion in the invisible hand condition than in the visible hand condition. Reaching error was higher in CS than in controls in the invisible hand condition but not in the visible hand condition. Average time taken to perform each trial was higher in CS than in controls in the invisible hand conditions but not in the visible hand condition. Conclusions: Reaching accuracy assessed by VR offers a non-invasive and rapid approach to quantifying fine motor functions in clinical settings. Furthermore, this technology enhances our understanding of proprioceptive function in patients with visuomotor disabilities by allowing the isolation of proprioception from vision. Future studies with larger cohorts and longitudinal designs will examine the quantitative changes in reaching accuracy after stroke and explore the long-term benefits of VR in functional recovery.

[Cerebellar cognitive affective syndrome and vertebrobasilar ischemia. From cerebello-cerebral diaschisis to "dysmetria of thought"].

Cerebellum, along with it' s role in coordinating motor functions, exercises a significant regulatory influence in fields of cognitive and affective functions. Therefore, studying the effect of cerebrovascular atherosclerotic pathology on mood and cognition should not be limited to stenotic dysfunctions of carotid arteries, but also extend its methodological framework to the consideration of the integrity of vertebrobasilar system (VBS), cerebellar perfusion and posterior cerebral circulation in general, as it has not been yet sufficiently addressed whether VBS insufficiency is associated with deterioration of patients' mental and emotional status and quality of life (QoL). Vertebrobasilar circulatory dysfunction has been pointed out, since decades, as a cause of progressive memory impairment and dementia, due to multiple infarcts in cerebral areas which are topographically critical for mental and emotional functions. Indicative of the pathophysiological and anatomic-functional association of VBS with these neuro-psychiatric domains are cerebellar cognitive-affective syndrome (CCAS) and crossed cerebello-cerebral diaschisis (CCCD). Mental and psychiatric components of CCAS, along with ataxic motor disability, constitute the conceptual hypothesis of "dysmetry of thought", while diagnostic significance of mental dysfunctions and psychopathological manifestations, in terms of symptoms preceding motor impairments that ascribe cerebellar malfunction in the epicenter of their pathophysiology, such as cerebellar ataxias, in which, early recognition of CCAS may facilitate therapeutic interventions aimed at improving QoL, reveal that cerebellar pathology, either of degenerative etiology or vascular substrate on the ground of vertebrobasilar insufficiency (VBI) or other surgical conditions of the posterior fossa, is associated with deterioration of patients' QoL which is related to significant impairments in their cognitive functions with (co)manifested emotional disorders. Studies in animal models also support these conclusions. Since VBI is responsible for a wide range of psychiatric and neurological symptoms, new findings concurred with current indications advocating that, without consideration of VBS disorders, it is impossible to clarify the connection of cerebral perfusion dysfunctions to neurocognitive deficits. The inclusion of cerebellar perfusion disorders in scientific research and clinical approaches to cognitive and affective disorders that may occur in patients with cerebrovascular lesions constitutes a paradigm of best clinical practices implementation and interdisciplinary convergence of neurosciences and vascular medicine.

Impaired Cortico-Thalamo-Cerebellar Integration Across Schizophrenia, Bipolar II, and Attention Deficit Hyperactivity Disorder Patients Suggests Potential Neural Signatures for Psychiatric Illness.

Understanding aberrant functional changes between brain regions has shown promise for characterizing and differentiating the symptoms associated with progressive psychiatric disorders. The functional integration between the thalamus and cerebellum significantly influences learning and memory in cognition. Observed in schizophrenic patients, dysfunction within the corticalthalamocerebellar (CTC) circuitry is linked to challenges in prioritizing, processing, coordinating, and responding to information. This study explored whether abnormal CTC functional network connectivity patterns are present across schizophrenia (SCHZ) patients, bipolar II disorder (BIPOL) patients, and ADHD patients by examining both task- and task-free conditions compared to healthy volunteers (HC). Leveraging fMRI data from 135 participants (39 HC, 27 SCHZ patients, 38 BIPOL patients, and 31 ADHD patients), we analyzed functional network connectivity (FNC) patterns across 115 cortical, thalamic, subcortical, and cerebellar regions of interest (ROIs). Guiding our investigation: First, do the brain regions of the CTC circuit exhibit distinct abnormal patterns at rest in SCHZ, ADHD, and BIPOL? Second, do working memory tasks in these patients engage common regions of the circuit in similar or unique patterns? Consistent with previous findings, our observations revealed FNC patterns constrained in the cerebellar, thalamic, striatal, hippocampal, medial prefrontal and insular cortices across all three psychiatric cohorts when compared to controls in both task and task-free conditions. Post hoc analysis suggested a predominance in schizophrenia and ADHD patients during rest, while the task condition demonstrated effects across all three disorders. Factor-by-covariance GLM MANOVA further specified regions associated with clinical symptoms and trait assessments. Our study provides evidence suggesting that dysfunctional CTC circuitry in both task-free and task-free conditions may be an important broader neural signature of psychiatric illness.

Cerebellum: From the identification of the cerebellar motor syndrome to the internal models.

Cerebellar circuitry is topographically arranged in closed loops with the cerebral cortex. The three cornerstones of clinical ataxia have emerged from studies on connectional anatomy and from clinical/neuropsychological observations, leading to the definition of clinical syndromes encountered in daily practice: (a) the cerebellar motor syndrome (CMS), (b) the vestibulocerebellar syndrome (VCS), and (c) the cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). These syndromes are either isolated or coexist, depending on the underlying pathological process and its degree of extension within the cerebellum. Dysmetria is the core feature of cerebellar deficits, encompassing motor dysmetria (hypermetria, hypometria) in CMS, oculomotor dysmetria in VCS, and dysmetria of thought in CCAS/SS. The leading hypothesis is that dysmetria results from errors in building or maintaining internal models, which are inherent to predictive behavior. Errors in prediction would lead to clumsiness and incoordination of limbs, oculomotor impairments, and aberrant cognitive/affective behavior. The cerebellum is currently viewed as a learning machine enriched with multiple plasticity mechanisms, allowing the permanent adaptation to the external world by generating and maintaining predictive operations, from motor to cognitive, affective, emotional, and social operations essential for daily human life.

ITPR1-associated spinocerebellar ataxia with craniofacial features-additional evidence for germline mosaicism.

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum-bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement-an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

The underpinnings of cerebellar ataxias.

The human cerebellum contains more than 60% of all neurons of the brain. Anatomically, the cerebellum is divided into 10 lobules (I-X). The cerebellar cortex is arranged into three layers: the molecular layer (external), the Purkinje cell layer and the granular layer (internal). Purkinje neurons and interneurons are inhibitory, except for granule cells. The layer of Purkinje neurons inhibit cerebellar nuclei, the sole output of the cerebellar circuitry, as well as vestibular nuclei. The cerebellum is arranged into a series of olivo-cortico-nuclear modules arranged longitudinally in the rostro-caudal plane. The cerebro-cerebellar connectivity is organized into multiple loops running in parallel. From the clinical standpoint, it is now considered that cerebellar symptoms can be gathered into 3 cerebellar syndromes: a cerebellar motor syndrome (CMS), a vestibulocerebellar syndrome (VCS) and a cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). CMS remains a cornerstone of modern clinical ataxiology, and relevant lesions involve lobules I-V, VI and VIII. The core feature of cerebellar symptoms is dysmetria, covering motor dysmetria (errors in the metrics of motion) and dysmetria of thought. The cerebellar circuitry plays a key-role in the generation and maintenance of internal models which correspond to neural representations reproducing the dynamic properties of the body. These models allow predictive computations for motor, cognitive, social, and affective operations. Cerebellar circuitry is endowed with noticeable plasticity properties.

Long-Lasting Efficacy of Radio Electric Asymmetric Conveyer Neuromodulation Treatment on Functional Dysmetria, an Adaptive Motor Behavior.

Background Fluctuating asymmetry (FA) is widely defined as the deviation from perfect bilateral symmetry and is considered an epigenetic measure of environmental stress. Rinaldi and Fontani hypothesized that the FA morpho-functional changes originate from an adaptive motor behavior determined by functional alterations in the cerebellum and neural circuits, not caused by a lesion, but induced by environmental stress. They called this phenomenon functional dysmetria (FD). On this premise, they developed the radio electric asymmetric conveyer (REAC) technology, a neuromodulation technology aimed at optimizing the best neuro-psycho-motor strategies in relation to environmental interaction. Aims Previous studies showed that specific REAC neuro postural optimization (NPO) treatment can induce stable FD recovery. This study aimed to verify the duration of the NPO effect in inducing the stable FD recovery over time. Materials and methods Data were retrospectively collected from a population of 29,794 subjects who underwent a specific semiological FD assessment and received the NPO treatment, regardless of the pathology referred. Results The analysis of the data collected by the various participants in the study led us to ascertain the disappearance of FD in 100% of the cases treated, with a stability of the result detected up to 18 years after the single administration of the REAC NPO treatment. Conclusions The REAC NPO neurobiological modulation treatment consisting of a single administration surprisingly maintains a very long efficacy in the correction of FD. This effect can be explained as the long-lasting capacity of the NPO treatment to induce greater functional efficiency of the brain dynamics as proven in previous studies.

Neuro Postural Optimization Neuromodulation Treatment of Radio Electric Asymmetric Conveyer Technology on Stress and Quality of Life in Institutionalized Children in a Capital City of the Brazilian Amazon.

Background The deviation from perfect bilateral symmetry is defined as fluctuating asymmetry (FA) and is a common phenomenon among living organisms. This deviation from perfection is thought to reflect the environmental pressures experienced during development and, therefore, the FA represents an epigenetic measure of the environmental stress, which affects all living beings from conception, progressively affecting all aspects of life. Rinaldi and Fontani hypothesized that the FA morpho-functional changes are originated by an adaptive motor behavior determined by functional alterations in the cerebellum and neural circuits, not caused by a lesion, but induced by the experienced environmental stress. They identified in the asymmetric activation of symmetrical muscle groups, detectable even in healthy subjects, the expression of the dysfunctional adaptation state of the subject and named this clinical semeiotic phenomenon functional dysmetria (FD). On these premises, they developed the radio electric asymmetric conveyer (REAC) technology, a neuromodulation technology aimed at optimizing the best neuro-psycho-motor strategies in relation to environmental interaction. Neuro postural optimization (NPO) is a neurobiological stimulation treatment administered with the REAC technology and it has been specifically studied to treat the state of dysfunctional adaptation that is revealed through the presence of FD. Aim The purpose of this study was to verify whether a single administration of the REAC NPO treatment can trigger the improvement of the capacity of stress management and the quality of life in a population of children housed in a group home in Macapá, Brazil. Materials and methods The sample of this study consisted of nine children (six boys and three girls) in the age group of 6-11 years, which represented the totality of the children present in the structure. The children was investigated for the assessment of the presence of functional dysmetria and with the Pediatric Quality of Life Inventory TM 4.0 (PedsQL) before and one week after the administration of the REAC NPO. Results The stable disappearance of FD was found in all children at follow-up. In addition, improvements were found in stress management and quality of life, in the physical, emotional, social, and scholastic aspects evaluated with PedsQL. Conclusions It was seen that the REAC NPO neurobiological modulation treatment induced the stable disappearance of FD and triggered the initial improvement of neurophysical aspects also in a population of children housed in a group home in the Amazon region of Macapá, Brazil.

Limb lengthening with PRECICE magnetic nail in pediatric patients: A systematic review.

BACKGROUND: Limb lengthening techniques play an increasingly important role in the pediatric orthopedic field. The principles of the osteogenesis distraction bonded traditionally with external fixators; however, the recent deployment of fully implantable systems has been able to overcome severities related to external fixators. The PRECICE® is an implantable limb lengthening intramedullary nail system that is remotely controlled and magnetically driven. AIM: To review the current literature available on this matter in order to assess the PRECICE clinical and radiological outcomes and its possible complications in a population of pediatric patients undergoing limb lengthening. METHODS: Only five studies met the inclusion criteria and were consequently included in the review for a total of 131 patients and 135 femurs. The clinical and radiological outcomes of interest were: the main lengthening obtained, the distraction rate, the period of time to full weight bearing, the consolidation index, and the Association for the Study and Application of Methods of Ilizarov score. RESULTS: In conclusion, data collected from the articles under investigation were comparable with the exception of the consolidation index. Unfortunately, the study population was too small and the patients' follow-up was too short to make definitive conclusions. CONCLUSION: This review shows that the PRECICE Nail System is still a therapeutic challenge in limb lengthening for pediatric orthopedic surgeons; however, careful pre-operative planning and an accurate surgical technique could allow the correction of more complex deformities with a low rate of complications.