Limb apraxia in individuals with multiple sclerosis: Is there a role of semi-immersive virtual reality in treating the Cinderella of neuropsychology?

BACKGROUND: Limb apraxia is an acquired cognitive-motor disorder characterized by spatial and temporal disorganization of limb movements, negatively affecting the quality of life of patients, including those with multiple sclerosis (MS). Although recent studies have shown the potential role of VR in increasing cognitive and motor functions, only a few studies have been carried out on the rehabilitation of upper limb apraxia. Hence, our study aims to evaluate the potential efficacy of VR training to improve upper limb ideomotor apraxia in patients with MS. METHODS: One hundred and six patients, affected by secondary progressive MS, who attended our Robotic and Behavioral Neurorehabilitation Service from March 2019 to February 2020, were enrolled in this study and randomly divided into two groups: the control group (CG: 53 patients) performed traditional therapy whereas the experimental group (EG:53 patients) received training using semi-immersive VR. All patients underwent the same amount of cognitive training, 3 times a week for 8 weeks. They were submitted to a specific neuropsychological assessment before (T0) and after the rehabilitation treatment (T1). RESULTS: The VR training led to a significant improvement in global cognitive functions, with regard to constructive and ideomotor apraxia. On the contrary, the CG achieved significant improvements only in ideomotor apraxia. Moreover, only in the EG, we observed an improvement in the mood at the end of training. CONCLUSION: The present study demonstrates that VR rehabilitation can be an effective tool for the treatment of apraxia, which is a neuropsychological problem often underestimated in MS patients. Further studies with long-term follow-up periods are needed to confirm the effect of this promising approach.

Clinical Screening for Posterior Cortical Atrophy.

BACKGROUND: Posterior cortical atrophy (PCA) is a progressive neurologic syndrome that presents with complex visual deficits. Although PCA is most commonly a form of Alzheimer disease (AD), its early diagnosis is usually delayed due to a lack of understanding for how best to clinically screen for the syndrome. OBJECTIVE: To identify neurobehavioral screening tasks for PCA-beyond simple visual constructions-that can be administered in clinic or at bedside. METHOD: We compared the performance of 12 individuals who met neuroimaging-supported consensus criteria for PCA with that of 12 matched individuals with typical AD (tAD) and 24 healthy controls (HC) on clinic/bedside tasks measuring (a) complex figure copying, (b) Balint syndrome, (c) visual object agnosia, (d) color identification, (e) figure-ground discrimination, (f) global-local processing, (g) dressing apraxia, (h) ideomotor apraxia, and (i) Gerstmann syndrome. RESULTS: All of the individuals with PCA were impaired on the figure-ground discrimination task compared with half of the tAD group and no HC. Approximately half of the PCA group had Balint syndrome, dressing apraxia, and ideomotor apraxia compared with none in the tAD group. Difficulty copying a complex figure, global-local processing impairment, and Gerstmann syndrome did not distinguish between the two dementia groups. CONCLUSION: The figure-ground discrimination task can be used successfully as an overall screening measure for PCA, followed by specific tasks for Balint syndrome and dressing and limb apraxia. Findings reinforce PCA as a predominant occipitoparietal disorder with dorsal visual stream involvement and parietal signs with spatiomotor impairments.

Delayed gait recovery by resolution of limb-kinetic apraxia in a chronic hemiparetic stroke patient: A case report.

RATIONALE: This paper reports on a chronic hemiparetic stroke patient who showed delayed gait recovery due to resolution of limb-kinetic apraxia (LKA). PATIENT CONCERNS: A 49-year-old man underwent comprehensive rehabilitation at a local rehabilitation hospital since 3 weeks after spontaneous intracerebral haemorrhage. However, he could not walk independently because of severe motor weakness in his right leg until 19 months after the onset. DIAGNOSIS: At the beginning of rehabilitation at our hospital (19 months after onset), we thought that he had the neurological potential to walk independently because the unaffected (right) corticospinal tract and corticoreticulospinal tract were closely related to the gait potential, representing intact integrities. As a result, we assumed that the severe motor weakness in the right leg was mainly ascribed to LKA. INTERVENTIONS: At our hospital, he underwent comprehensive rehabilitation including increased doses of dopaminergic drugs (pramipexole, ropinirole, amantadine, and carbidopa/levodopa). OUTCOMES: After 10 days to our hospital, he could walk independently on an even floor with verbal supervision, concurrent with motor recovery of the right leg. After 24 days after hospital admission, he could walk independently on an even floor. LESSONS: We believe that the resolution of LKA in his right leg by the administration of adequate doses of dopaminergic drugs was the main reason for the delayed gait recovery in this patient. The results suggest the importance of detecting the neurological potential for gait ability of a stroke patient who cannot walk after the gait recovery phase and the causes of gait inability for individual patients.

Kinetic Analysis of a Cysteine-Derived Thiyl-Catalyzed Asymmetric Vinylcyclopropane Cycloaddition Reflects Numerous Attractive Noncovalent Interactions.

Kinetic studies of a vinylcyclopropane (VCP) cycloaddition, catalyzed by peptide-based thiyl radicals, are described. Reactions were analyzed by using reaction progress kinetic analysis, revealing that ring-opening of the VCP is both rate- and enantio-determining. These conclusions are further corroborated by studies involving racemic and enantiopure VCP starting material. Noncovalent interactions play key roles throughout: both the peptide catalyst and VCP exhibit unproductive self-aggregation, which appears to be disrupted by binding between the catalyst and VCP. This in turn explains the requirement for the key catalyst feature, a substituent at the 4-position of the proline residue, which is required for both turnover/rate and selectivity.

Improvement in callosal disconnection syndrome with recovery of callosal connectivity.

Recent advancements in radiological techniques have enabled the observation of the topographic distribution of the human corpus callosum. However, its functional connectivity remains to be elucidated. The symptoms of callosal disconnection syndrome (CDS) can potentially reveal the functional connections between the cerebral hemispheres. Herein, we report a patient with CDS, whose callosal lesion was restricted to the posterior midbody, isthmus, and an anterior part of the dorsal splenium. A 53-year-old right-handed woman demonstrated CDS following cerebral infarction associated with subarachnoid hemorrhage. She exhibited CDS including ideomotor apraxia, and tactile anomia with the left hand, cross-replication of hand postures, cross-localization of the fingers, and constructional impairment with the right hand. Six months after onset, the left-handed ideomotor apraxia on imitation improved, but that to command did not, which indicated the difference in the nature of the transcallosal connections between ideomotor apraxia on imitation and ideomotor apraxia to command. Longitudinal CDS observation and corpus callosum tractography will prove useful in expanding our understanding of the nature of the organization of interhemispheric information transference.

Efficacy of virtual reality therapy in ideomotor apraxia rehabilitation: A case report.

RATIONALE: We report the possible therapeutic efficacy of immersive virtual reality (VR) rehabilitation for the treatment of ideomotor apraxia in a patient with stroke. PATIENT CONCERNS: A 56-year-old man with sudden weakness of his left side caused by right frontal, parietal, and corpus callosal infarction was transferred to rehabilitation medicine center for intensive rehabilitation. Although his left-sided weakness had almost subsided 10 days after the onset of symptoms, he presented difficulty using his left hand and required assistance in most activities of daily living. DIAGNOSES: Ideomotor apraxia in a patient with right hemispheric infarction. INTERVENTIONS: VR content was displayed to the study participants using a head-mounted display that involved catching of moving fish in the sea by grasping. Before and after of rehabilitative intervention including VR, functional measurements incorporating the Test of Upper Limb Apraxia (TULIA) were conducted. To directly compare therapeutic potencies under different conditions, success rates of consecutive grasping gesture performance were observed in VR, conventional occupational therapy setting, and augmented reality intervention. OUTCOMES: The patient demonstrated remarkable amelioration of apraxic symptoms while performing the task in the VR environment. At 1 and 3 months after the training, he showed significant improvement in most functions, and the TULIA score increased to 176 from 121 at the initiation of therapy. The number of successful grasps during 30 trials of each grasp trial was 28 in VR, 8 in the occupational therapy setting, and 20 in augmented reality. LESSONS: This case report suggests the possible therapeutic efficacy of immersive VR training as a rehabilitative measure for ideomotor apraxia.

Back in control of intentional action: Improvement of ideomotor apraxia by mirror box treatment.

OBJECTIVES: A novel method of rehabilitation for ideomotor apraxia (IMA), using a modified version of the mirror box (MB), is proposed. The rationale is based on the theory that disrupted body representation occurs in IMA and that MB training may improve body representation. In the present MB training, patients observed and reproduced movements made by the experimenter in a mirror. The visual perspective gave the illusory sensation of seeing one's own affected hand in the mirror. METHODS: Thirteen patients were included in the study; apraxia was measured four times: i) at baseline; ii) after a week of unspecific poststroke rehabilitation (rest); iii) after a week of imitation training for apraxia, used as a control; and iv) after a week of MB training. Imitation and mirror box training were presented in counterbalanced order between participants. The effect of the mirror box on a measure of body representation was also assessed. RESULTS: The results show that MB training improved apraxia when compared to the outcomes in both the imitation and rest conditions. The improvement correlates with the impact of the mirror box on the body representation (i.e., the degree of embodiment). CONCLUSIONS: MB training shows promising effects in promoting recovery from apraxia. The hypothesis is that the mirror box triggers a quickly generated sense of embodiment of the reflected moving arm into the observer's body representation. This embodiment of the visuomotor features of the observed movements would positively affect motor programming, promoting motor improvement. Crucially, this effect seems to extend to actions performed outside the mirror box setup, enhancing patients' performance on an apraxia test.

A connectivity model of the anatomic substrates underlying ideomotor apraxia: A meta-analysis of functional neuroimaging studies.

BACKGROUND: Patients with ideomotor apraxia (IMA) present with selective impairments in higher-order motor cognition and execution without damage to any motor or sensory pathways. Although extensive research has been conducted to determine the regions of interest (ROIs) underlying these unique impairments, previous models are heterogeneous and may be further clarified based on their structural connectivity, which has been far less described. OBJECTIVE: The goal of this research is to propose an anatomically concise network model for the neurophysiologic basis of IMA, specific to the voluntary pantomime, imitation and tool execution, based on intrinsic white matter connectivity. METHODS: We utilized meta-analytic software to identify relevant ROIs in ideomotor apraxia as reported in the literature based on functional neuroimaging data with healthy participants. After generating an activation likelihood estimation (ALE) of relevant ROIs, cortical parcellations overlapping the ALE were used to construct an anatomically precise model of anatomic substrates using the parcellation scheme outlined by the Human Connectome Project (HCP). Deterministic tractography was then performed on 25 randomly selected, healthy HCP subjects to determine the structural connectivity underlying the identified ROIs. RESULTS: 10 task-based fMRI studies met our inclusion criteria and the ALE analysis demonstrated 6 ROIs to constitute the IMA network: SCEF, FOP4, MIP, AIP, 7AL, and 7PC. These parcellations represent a fronto-parietal network consisting mainly of intra-parietal, U-shaped association fibers (40%) and long-range inferior fronto-occipital fascicle (IFOF) fibers (50%). These findings support previous functional models based on dual-stream motor processing. CONCLUSION: We constructed a preliminary model demonstrating the underlying structural interconnectedness of anatomic substrates involved in higher-order motor functioning which is seen impaired in IMA. Our model provides support for previous dual-stream processing frameworks discussed in the literature, but further clarification is necessary with voxel-based lesion studies of IMA to further refine these findings.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Motor sequence learning in patients with ideomotor apraxia: Effects of long-term training.

Recent studies show that limb apraxia is a quite frequent, yet often underdiagnosed, higher motor impairment following stroke. Because it adversely affects every-day life and personal independence, successful rehabilitation of apraxia is essential for personal well-being. Nevertheless, evidence of long-term efficacy of training schemes and generalization to untrained actions is still scarce. One possible reason for the tendency of this neurological disorder to persist may be a deficit in planning, conceptualisation and storage of complex motor acts. This pilot study aims at investigating explicit motor learning in apractic stroke patients. In particular, we addressed the ability of apractic patients to learn and to retain new explicit sequential finger movements across 10 training sessions over a 3-week interval. Nine stroke patients with ideomotor apraxia in its chronic stage participated in a multi-session training regimen and were included in data analyses. Patients performed an explicit finger sequence learning task (MSLT - motor sequence learning task), which is a well-established paradigm to investigate motor learning and memory processes. Patients improved task performance in terms of speed and accuracy across sessions. Specifically, they showed a noticeable reduction in the mean time needed to perform a correct sequence and the number of erroneous sequences. We found also a trend for improved performance at the Goldenberg apraxia test protocol: "imitation of meaningless hand and finger gestures" relative to when assessed before the MSLT training. Patients with ideomotor apraxia demonstrated the ability to acquire and maintain a novel sequence of movements; and, this training was associated with hints towards improvement of apraxia symptoms.

Body representation in people with apraxia post Stroke- an observational study.

Objective: To investigate how two types of body representation (body schema and body image) were affected in people with and without apraxia following a supratentorial stroke.Design: Observational cross-sectional studySetting: Level 1 Specialist Neurological Rehabilitation UnitParticipants: 30 participants post-stroke diagnosed with (n = 10) and without apraxia (n = 20) according to a modified version of the short Ideomotor Apraxia Test.Interventions: Not applicableMain Outcome Measures: Body schema assessed using the hand laterality recognition test and body part knowledge test; Implicit body image assessed using the sidedness test.Results: Left-sided lesions were more common in the apraxic group. Compared to people without apraxia post-stroke, those with apraxia showed significantly reduced accuracy and longer reaction times on the hand laterality test and fewer correct responses on the body part knowledge test. There was no between-groups difference in the sidedness test.Conclusions: People with apraxia showed deficits in online body representations (body schema) that are used to plan and execute actions. Future research studies could target body schema deficits as an adjunct in the rehabilitation of apraxia.

Complete monoplegia due to limb-kinetic apraxia in a patient with traumatic brain injury: A case report.

RATIONALE: Limb-kinetic apraxia (LKA) is a disorder of movement execution that is a result of injury to the corticofugal tracts (CFTs) from the secondary motor area. We report on a patient with traumatic brain injury (TBI) and complete monoplegia due to LKA, which was mainly ascribed to injury of the CFT from the secondary motor area using diffusion tensor tractography. PATIENT CONCERNS: A 35-year-old male was struck by a car from the side during riding an autocycle and received direct head trauma as a result of falling to ground. He lost consciousness for approximately 1 month and experienced continuous post-traumatic amnesia after the accident. The patient's Glasgow Coma Scale score was 3 and he showed quadriparesis including complete monoplegia of his left arm since the onset of TBI. DIAGNOSES: The patient diagnosed complete monoplegia due to LKA after traumatic brain injury. INTERVENTIONS: He underwent conservative management for TBI followed by rehabilitation at approximately 2 months after onset. OUTCOMES: At 32-month after onset, weakness on left arm (Manual Muscle Test [MMT]:0) and partial weakness of left leg (MMT:3). OUTCOMES: Results of electromyography and nerve conduction studies of left extremities were normal. Motor evoked potential values obtained from the abductor pollicis brevis muscle (APB) were: right APB latency 22.3msec, amplitude 1.6mV; left APB latency 22.8msec, amplitude 1.5mV. After 2 weeks of administration of dopaminergic drugs for improvement of LKA, left arm weakness had recovered to level that permitted movement against gravity (MMT:3). Diffusion tensor tractography at 32-month after onset showed right corticospinal tract discontinuation at the pontine level and partial tearing of the left corticospinal tract at the subcortical white matter. In addition, the left CFT from the supplementary motor area showed partial tearing at the subcortical white matter. LESSONS: The LKA due to injury of the left supplementary motor area-CFT was demonstrated in a patient with complete monoplegia following TBI. Accurate diagnosis of LKA is important for successful rehabilitation because LKA is known to respond to dopaminergic drug treatment.

Motor recovery of hemiparetic leg by improvement of limb-kinetic apraxia in a chronic patient with traumatic brain injury: A case report.

RATIONALE: Limb-kinetic apraxia (LKA), a kind of apraxia, means the inability to perform precise and voluntary movements of extremities resulting from injury of the premotor cortex (PMC) or the corticofugal tract (CFT) from the PMC. Diagnosis of LKA is made by observation of movements without specific assessment tools. PATIENT CONCERNS: A 44-year-old male underwent conservative management for traumatic intracerebral hemorrhage in the left basal ganglia and subarachnoid hemorrhage due to a pedestrian-car crash. When he was admitted to the rehabilitation department of a university hospital after 41 months after onset, he presented with right hemiparesis (Medical Research Council (MRC): shoulder abductor; 3, elbow flexor; 3, finger extensor; 0, hip flexor; 2- [range: 30°], knee extensor; 1 and ankle dorsiflexor; 3-). In addition, he exhibited slow, clumsy, and mutilated movements when performing movements of his right ankle. DIAGNOSES: The patient was diagnosed as traumatic brain injury (TBI). INTERVENTIONS: Clinical assessments and DTI were performed at 41 and 44 months after onset. During three months, rehabilitative therapy was performed including dopaminergic drugs (pramipexole 2.5 mg, ropinirole 2.5 mg, and amantadine 300 mg, and carbidopa/levodopa 75 mg/750 mg). OUTCOMES: The right leg weakness slowly recovered during 3 months, until 44 months after the initial injury (MRC: shoulder abductor, 3; elbow flexor, 3; finger extensor, 0; hip flexor, 3; knee extensor, 3; and ankle dorsiflexor, 3+). The fiber number of the right corticospinal tract (CST) was decreased on 44-month diffusion tensor tractography (DTT) (1319) compared with 41-month DTT (1470) and the left CST was not reconstructed on both DTTs. The fiber number of both CRTs were decreased on 44-month DTT (right: 1547, left: 698) than 41-month DTT (right: 3161, left: 1222). LESSONS: A chronic patient with TBI showed motor recovery of the hemiparetic leg by improvement of LKA after rehabilitation. This results have important implications for neurorehabilitation.

Discovery of Apraxia (Historical Note) / Descoberta da apraxia (Nota Histórica)

Skilled movements certainly exist since the dawn of the humans, embedded in the actions of daily living, and also represented by tools and weapons making and use, as well as by artistic activities as drawing and engraving. A very long period of time elapsed until such actions were recognized as special, and the designation 'praxis' was attributed to such ability of produce refined movements. Another long time passed, and only recently disturbances of such actions caused by brain lesions were identified, leading to the concept of 'apraxia'. Studies on this subject progressed quickly, and in a few decades reached the state resembling to what is seen nowadays.

Movimentos hábeis certamente existem desde a aurora dos humanos, incluídos nas ações da vida diária e também representados na feitura e uso de ferramentas e de armas, assim como por atividades artísticas como desenhar e gravar. Decorreu um longo período de tempo até que tais ações fossem reconhecidas como especiais e a designação de 'praxia' foi atribuída para tais habilidades para produzir movimentos refinados. Outro tempo prolongado passou, e apenas recentemente desordens de tais ações causadas por lesões cerebrais fossem identificadas, levando ao conceito de 'apraxia'. Estudos sobre esse assunto progrediram rapidamente e em poucas décadas alcançaram o estado que se assemelha ao que é visto atualmente.

The Effectiveness of Action Observation Therapy Based on Mirror Neuron Theory in Chinese Patients with Apraxia of Speech after Stroke.

OBJECTIVE: The present study aimed to evaluate the efficacy of action observation therapy (AOT) on apraxia of speech (AOS) in patients after stroke. MATERIALS AND METHODS: Forty-two patients diagnosed with AOS after stroke were randomly divided into an experimental group (n = 21) and a control group (n = 21). Both groups received 30 min of conventional language therapy twice daily, 5 days a week for 4 weeks. The patients in the experimental group additionally received 20 min of AOT before 10 min language therapy each day. The speech function and aphasia severity of the 2 groups were assessed using the speech apraxia assessment method of the China Rehabilitation Research Center, Western Aphasia Battery (WAB), and the Boston Diagnostic Aphasia Examination before and after treatment. RESULTS: AOS and WAB scores increased significantly after treatment in both groups (p < 0.05). AOS and WAB scores exhibited significant differences between the experimental group and the control group after training (p < 0.05). The response rate in the experimental group was significantly higher than that in the control group (p < 0.05). CONCLUSION: AOT based on mirror neuron theory may improve language function in patients with AOS after stroke.

A pilot study of fascia Bowen therapy for 8-11 year-old boys with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD), also known as dyspraxia, is a disorder emerging in childhood characterised by motor skill impairments. The motor difficulties often produce negative effects in other areas of life, such as poor self-esteem and reduced social interactions. One treatment used for DCD is fascia Bowen therapy, which involves stimulating the fascia tissues of the body using finger and thumb rolling movements over the skin to improve overall muscle movement. However, no studies to date have been reported testing the effectiveness of fascia Bowen in DCD. METHODS: The present pilot study tested the effectiveness of 6 weeks of fascia Bowen in 10 boys aged 8-11 years with DCD. None of the boys had ever received treatment in any form before this study. Motor skills were assessed using the Movement Assessment Battery for Children-2 (MABC-2) and the DCD questionnaire, and psycho-social functioning was measured using the Self-Perception Profile, Spence Social Skills Questionnaire, and Strengths and Difficulties Questionnaire. All measures of interest were assessed before and after the therapy. RESULTS: Results showed significant improvement in motor function post-intervention, with 60% of the children no longer clinically being classified as having a movement difficulty on the MABC-2. However, no significant improvements were seen in psycho-social measures, at least within the short time-frame of the therapy in the current study. CONCLUSIONS: The current pilot study revealed improvements in motor functioning after fascia Bowen therapy, across both performance and questionnaire measures, but that these improvements did not extend to wider areas of life. Further research in DCD is needed to test the effectiveness of fascia Bowen in larger studies with expanded ages and both genders over longer periods, including the generalisation of results of these longer interventions to different areas of life beyond motor ability.

Parietal Involvement in Constructional Apraxia as Measured Using the Pentagon Copying Task.

Deficits in copying ("constructional apraxia") is generally defined as a multifaceted deficit. The exact neural correlates of the different types of copying errors are unknown. To assess whether the different categories of errors on the pentagon drawing relate to different neural correlates, we examined the pentagon drawings of the MMSE in persons with subjective cognitive complaints, mild cognitive impairment, or early dementia due to Alzheimer's disease. We adopted a qualitative scoring method for the pentagon copy test (QSPT) which categorizes different possible errors in copying rather than the dichotomous categories "correct" or "incorrect." We correlated (regional) gray matter volumes with performance on the different categories of the QSPT. Results showed that the total score of the QSPT was specifically associated with parietal gray matter volume and not with frontal, temporal, and occipital gray matter volume. A more fine-grained analysis of the errors reveals that the intersection score and the number of angles share their underlying neural correlates and are associated with specific subregions of the parietal cortex. These results are in line with the idea that constructional apraxia can be attributed to the failure to integrate visual information correctly from one fixation to the next, a process called spatial remapping.

Basal ganglia involvement in ARX patients: The reason for ARX patients very specific grasping?

The ARX (Aristaless Related homeoboX) gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the ARX gene, a duplication of 24 base pairs (c.429_452dup24) in exon 2, results in a recognizable syndrome in which patients present ID without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip, described as developmental Limb Kinetic Apraxia (LKA). In this study, we first present ARX expression during human fetal brain development showing that it is strongly expressed in GABAergic neuronal progenitors during the second and third trimester of pregnancy. We show that although ARX expression strongly decreases towards the end of gestation, it is still present after birth in some neurons of the basal ganglia, thalamus and cerebral cortex, suggesting that ARX also plays a role in more mature neuron functioning. Then, using morphometric brain MRI in 13 ARX patients carrying c.429_452dup24 mutation and in 13 sex- and age-matched healthy controls, we show that ARX patients have a significantly decreased volume of several brain structures including the striatum (and more specifically the caudate nucleus), hippocampus and thalamus as well as decreased precentral gyrus cortical thickness. We observe a significant correlation between caudate nucleus volume reduction and motor impairment severity quantified by kinematic parameter of precision grip. As basal ganglia are known to regulate sensorimotor processing and are involved in the control of precision gripping, the combined decrease in cortical thickness of primary motor cortex and basal ganglia volume in ARX dup24 patients is very likely the anatomical substrate of this developmental form of LKA.

A progressive breakdown of the body in space.

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. The final diagnosis was that of a corticobasal degeneration, where the rare occurrence of a progressively emerging syndrome of self-management loss within peripersonal space is observed.

Deficient supplementary motor area at rest: Neural basis of limb kinetic deficits in Parkinson's disease.

Parkinson's disease (PD) patients frequently suffer from limb kinetic apraxia (LKA) affecting quality of life. LKA denotes an impairment of precise and independent finger movements beyond bradykinesia, which is reliably assessed by coin rotation (CR) task. BOLD fMRI detected activation of a left inferior parietal-premotor praxis network in PD during CR. Here, we explored which network site is most critical for LKA using arterial spin labeling (ASL). Based on a hierarchical model, we hypothesized that LKA would predominantly affect the functional integrity of premotor areas including supplementary motor areas (SMA). Furthermore, we suspected that for praxis function with higher demand on temporal-spatial processing such as gesturing, inferior parietal lobule (IPL) upstream to premotor areas would be essential. A total of 21 PD patients and 20 healthy controls underwent ASL acquisition during rest. Behavioral assessment outside the scanner involved the CR, finger tapping task, and the test of upper limb apraxia (TULIA). Whole-brain analysis of activity at rest showed a significant reduction of CR-related perfusion in the left SMA of PD. Furthermore, the positive correlation between SMA perfusion and CR, seen in controls, was lost in patients. By contrast, TULIA was significantly associated with the perfusion of left IPL in both patients and controls. In conclusion, the findings suggest that LKA in PD are linked to an intrinsic disruption of the left SMA function, which may only be overcome by compensatory network activation. In addition, gestural performance relies on IPL which remains available for functional recruitment in early PD.