Cerebellum and apraxia

Classical tenits posit that the role of the cerebellum is limited to pure sensorimotor control. However, evidence from clinical and imaging studies shows that the cerebellum is crucially involved in nonmotor cognitive and affective functions. Schmahmann and Sherman (1998) [1] introduced the cerebellar cognitive affective syndrome (CCAS), characterised by executive, visuo-spatial, affective and linguistic impairments caused by cerebellar pathology. Apraxia, as a planning, organisation and execution disorder of a skilled motor action (not caused by motor, sensory or intellectual impairment) [2], may be regarded to form part of the executive cluster of CCAS. Indeed, several anatomoclinical studies have confirmed involvement of the cerebellum in at least some types of apraxia, which adds to the nonmotor role of the cerebellum. According to Hugo Liepmann [3], apraxia is thought to evolve from a disruption of the creation, activation or retrieval of movement formulae. These formulae represent the idea of a movement as a visual or acoustic image and are stored in the left parietal lobe. The left prefrontal area subsequently associates these formulae with an inherently stored innervatory pattern to transfer the information to the left primary motor areas. The corpus callosum transfers this information to the right motor cortex if the movement is to be executed by the left limb [3]. Based on some recent clinical evidence we hypothesize that the cerebellum forms an intrinsic part of this connectionist model of Liepmann

Clinicians' views of using cortical auditory evoked potentials (CAEP) in the permanent childhood hearing impairment patient pathway

Objective: To obtain clinicians' views on the use of cortical auditory evoked potentials (CAEP) in the clinical pathway. Design: A questionnaire aimed at clinicians who use the HEARLab system with the Aided Cortical Assessment (ACA) Module. Results compared for Australians (where HEARLab produced) to other countries. Sample: The questionnaire was completed by 49 clinicians; 33 from Australia and 13 clinicians outside of Australia and 3 clinicians, destination unknown. Results: The findings of this research demonstrated that clinicians using CAEPs found them valuable for clinical practice. CAEPs were used to verify or modify hearing aid fittings and were used for counselling parents to reinforce the need for hearing aids. With the use of speech token as the stimulus clinicians had more relevant information to increase confidence in decision-making on paediatric hearing management. Conclusions: The main benefit from the use of CAEPs (using speech token stimuli) was for infant hearing aid fitting programmes, to facilitate earlier decisions relating to hearing aid fitting, for fine-tuning the aids and as an additional measure for cochlear implant referrals

The undervalued potential of positional therapy in position-dependent snoring and obstructive sleep apnea—a review of the literature

PURPOSE: Research during the past 10–20 years shows that positional therapy (PT) has a significant influence on the apnea–hypopnea index. These studies are predominantly performed as case series on a comparably small number of patients. Still, results have not found their way into the daily diagnostic and treatment routine. An average of 56 % of patients with obstructive sleep apnea (OSA) have position-dependent OSA (POSA), commonly defined as a difference of 50 % or more in apnea index between supine and non-supine positions. A great deal could be gained in treating patients with POSA with PT. The aim of this paper was to perform a thorough review of the literature on positional sleep apnea and its therapy. METHODS: A broad search strategy was run electronically in the MEDLINE and EMBASE databases using synonyms for position and sleep apnea. RESULTS: Sixteen studies were found which examined the effect of PT on OSA. In this literature review, we discuss the various techniques, results, and compliance rates. CONCLUSION: Long-term compliance for PT remains an issue, and although remarkable results have been shown using innovative treatment concepts for PT, there is room for both technical improvement of the devices and for further research

Cerebellar induced differential polyglot aphasia: a neurolinguistic and fMRI study

Research has shown that linguistic functions in the bilingual brain are subserved by similar neural circuits as in monolinguals, but with extra-activity associated with cognitive and attentional control. Although a role for the right cerebellum in multilingual language processing has recently been acknowledged, a potential role of the left cerebellum remains largely unexplored. This paper reports the clinical and fMRI findings in a strongly right-handed (late) multilingual patient who developed differential polyglot aphasia, ataxic dysarthria and a selective decrease in executive function due to an ischemic stroke in the left cerebellum. fMRI revealed that lexical-semantic retrieval in the unaffected L1 was predominantly associated with activations in the left cortical areas (left prefrontal area and left postcentral gyrus), while naming in two affected non-native languages recruited a significantly larger bilateral functional network, including the cerebellum. It is hypothesized that the left cerebellar insult resulted in decreased right prefrontal hemisphere functioning due to a loss of cerebellar impulses through the cerebello-cerebral pathways

A review of the anti-tumor potential of current therapeutics targeting the mitochondrial protease ClpP in H3K27-altered, diffuse midline glioma

Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors recognized as the leading cause of cancer-related death in children. DMGs are high-grade gliomas (HGGs) diagnosed along the brain's midline. Euchromatin is the hallmark feature of DMG, caused by global hypomethylation of H3K27 either through point mutations in histone H3 genes (H3K27M), or by overexpression of the enhancer of zeste homolog inhibitory protein (EZHIP). In a clinical trial for adults with progressive HGGs, a 22-year-old patient with a thalamic H3K27-altered DMG, showed remarkable clinical and radiological responses to dordaviprone (ONC201). This response in a H3K27-altered HGG patient, coupled with the lack of response of patients harboring wildtype-H3 tumors, has increased the clinical interest in dordaviprone for the treatment of DMG. Additional reports of clinical benefit have emerged, but research defining mechanisms of action (MOA) fall behind dordaviprone's clinical use, with biomarkers of response unresolved. Here, we summarize dordaviprone's safety, interrogate its preclinical MOA- identifying the mitochondrial protease 'ClpP' as a biomarker of response, and discuss other ClpP-agonists, expanding the arsenal of potential weapons in the fight against DMG. Finally, we discuss combination strategies including ClpP-agonists, and its immunomodulatory effects suggestive of a role for the tumor microenvironment in DMG patients' response

Metal Cation Pre-Intercalated Ti3C2Tx MXene as Ultra-High Areal Capacitance Electrodes for Aqueous Supercapacitors

Two-dimensional transition-metal carbides and nitrides “MXenes” have demonstrated great potential as electrode materials for electrochemical energy storage systems. This is especially true for delaminated Ti3C2Tx, which already shows outstanding gravimetric and volumetric capacitance, with areal capacitance limited by thickness (only a few microns). However, the performance of multilayer Ti3C2Tx has been more modest. Here, we report on using metal cation (viz., Na+, K+, and Mg2+) pre-intercalated multilayer Ti3C2Tx as electrodes for aqueous supercapacitors. These electrodes are scalable and amenable to roll-to-roll manufacturing, with adjustable areal loadings of 5.2 to 20.1 mg/cm2. K–Ti3C2Tx exhibited the highest capacitances at different scan rates. A gravimetric capacitance comparable to that of delaminated MXene of up to 300 F/g was achieved for multilayer K–Ti3C2Tx but with an outstanding ultra-high areal capacitance of up to 5.7 F/cm2, which is 10-fold higher than the 0.5 F/cm2 of delaminated MXene and exceeds the 4.0 F/cm2 of microengineered MXene electrodes