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1.
Skeletal Radiol ; 51(3): 525-533, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34216246

ABSTRACT

OBJECTIVES: To assess the diagnostic accuracy of MRI in diagnosing ramp lesions in patients with an acute lesion of the anterior cruciate ligament (ACL). MATERIALS AND METHODS: All consecutive patients over 15 years of age who underwent surgical repair of the ACL at a single hospital between January and May 2019, with MRI data available, were included in this retrospective study, except patients who had previous knee surgery. The gold standard was arthroscopic evaluation. Two trained radiologists with 5 and 14 years of experience did a blinded review of the MRIs. The following pathological signs were studied: complete fluid filling between the capsule and the posterior horn of the medial meniscus, irregular appearance of the posterior wall of the medial meniscus, oedema of the capsule, fluid hyperintensity in contact with the medial meniscus and anterior subluxation of the medial meniscus. Logistic regressions in univariate then multivariate analysis were carried out and measures of diagnostic accuracy and interobserver agreement were calculated with R software (version 3.6). RESULTS: Fifty-seven patients were included. Twelve had a ramp lesion diagnosed by arthroscopy (21%). Only complete fluid hyperintensity between the posterior horn of the medial meniscus and the capsule was significantly associated with ramp lesions (P value < 0.01). The diagnostic accuracy of this specific sign was moderate, with a specificity of 84%, sensitivity of 75%, PPV of 56%, NPV of 93% and a good level of inter-observer agreement (k = 0.79). CONCLUSION: The complete fluid filling is the only significant pathological MRI sign for ramp lesions, with moderate accuracy.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Tibial Meniscus Injuries , Anterior Cruciate Ligament Injuries/surgery , Arthroscopy , Humans , Magnetic Resonance Imaging , Menisci, Tibial/surgery , Retrospective Studies , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery
2.
Diagn Interv Imaging ; 102(4): 241-245, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33008783

ABSTRACT

PURPOSE: The purpose of this study was to analyze the potential of ultrasound with a high frequency probe (24-MHz) in the assessment of the long thoracic nerve (LTN) and describe ultrasonographic landmarks that can be used for standardization. MATERIAL AND METHODS: Ultrasonography analysis of the LTN was done on 2 LTNs in a cadaver specimen and then on 30 LTNs in 15 healthy volunteers (12 men, 3 women; mean age, 28.8±3.8 [SD] years; age range: 24-39 years) by two independent radiologists (R1 and R2) using a 24-MHz probe. Interrater agreement was assessed using Kappa test (K) and intraclass correlation coefficient (ICC). RESULTS: In the cadaver, dissection confirmed that the India ink was injected near the LTN in the middle scalene muscle. In volunteers, visibility of the LTN above the clavicle was highly reproducible for the branches arising from C5 (R1: 87% [26/30]; R2: 90% [27/30]; K=0.83) and from C6 (R1: 100% [30/30]; R2: 97% [29/30]; K=0.94). Where the nerve emerged from the middle scalene muscle, the mean diameter was 0.85±0.24 (SD) mm (range: 0.4-1.6mm) for R1 and 0.9±0.23 (SD) mm (range: 0.4-1.7mm) for R2 (ICC: 0.96; 95% CI: 0.92-0.98%). Along the thoracic wall, where LTN run along the lateral thoracic artery, the mean diameter was 0.83±0.19 (SD) mm (range: 0.5-1.27mm) for R1 and 0.89±0.21 (SD) mm (range: 0.6-1.2mm) for R2 (ICC: 0.86; 95% CI: 0.72-0.93%). CONCLUSION: The LTN can be analyzed with ultrasound using high-frequency probe by using the C5 and C6 roots, the middle scalene muscle above the clavicle and the lateral thoracic artery on the chest wall as landmarks.


Subject(s)
Thoracic Nerves , Adult , Cadaver , Female , Humans , Male , Thoracic Nerves/anatomy & histology , Thoracic Nerves/diagnostic imaging , Ultrasonography , Young Adult
4.
Diagn Interv Imaging ; 98(12): 873-879, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29102312

ABSTRACT

PURPOSE: The aim of the study was to evaluate the assessability of the suprascapular nerve (SSN) by ultrasonography in cadavers and healthy volunteers. MATERIALS AND METHODS: With ultrasonography guidance, needles were placed at origin of the SSN of four cadavers and evaluated by dissection. Two blinded radiologists performed 60 ultrasonography scans in 30 healthy volunteers to study the entire SSN at five anatomical landmarks. RESULTS: Dissection revealed that the needles were correctly located at the nerve's origin. There were no significant differences between the two radiologists' measurements of nerve size and depth. The interobserver correlation for the description of the nerve at the five predefined anatomical landmarks was very good (ICC=0.7-1). CONCLUSION: Five anatomical landmarks were used to analyze the SSN with ultrasonography. Its supraclavicular portion was easier to describe than its scapular portion; a segment of the SSN was not visible between these two portions.


Subject(s)
Brachial Plexus/anatomy & histology , Brachial Plexus/diagnostic imaging , Adult , Aged , Aged, 80 and over , Cadaver , Female , Humans , Male , Middle Aged , Scapula , Ultrasonography
6.
Clin Anat ; 30(6): 747-752, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28612344

ABSTRACT

Anatomical variations in the suprascapular nerve (SSN) and its depth in the suprascapular notch can make it difficult to target with ultrasonography (US). One alternative could be a proximal approach to the SSN, if US provides a reliable description of its origin (orSSN). The primary objective of this study was to demonstrate that US can reliably locate the orSSN. The secondary objective was to describe the features of the proximal SSN. Seventy brachial plexuses (BPs) from 30 healthy volunteers (60 BPs) and 5 cadavers (10 BPs) were included. There were two parts to this study: (1) description of the proximal SSN in healthy volunteers using US to determine the diameter, depth and location of the orSSN; (2) targeting of the orSSN with US in cadaver limbs to determine its distance from the needle, ink marking and locating the orSSN. In Part I, the diameter of the orSSN averaged 1.33 mm (1-9 mm) and its depth averaged 5.12 mm (2.7-10.6 mm). The orSSN was located in the upper trunk of the BP (53) or its posterior division (7). In Part II, the orSSN was successfully targeted in nine of the 10 specimens by US; the needle/orSSN distance averaged 3.8 mm (0-8 mm). The implanted needle was at the orSSN in two cases, proximal to it in seven and distal to it in one. US is a valid modality for describing and pinpointing the orSSN, irrespective of patient morphology. Clin. Anat. 30:747-752, 2017. © 2017Wiley Periodicals, Inc.


Subject(s)
Brachial Plexus/anatomy & histology , Brachial Plexus/diagnostic imaging , Ultrasonography/methods , Adult , Aged , Aged, 80 and over , Cadaver , Female , Healthy Volunteers , Humans , Male , Middle Aged , Shoulder/innervation
7.
Diagn Interv Imaging ; 97(7-8): 749-65, 2016.
Article in English | MEDLINE | ID: mdl-27452631

ABSTRACT

Magnetic resonance imaging has now an indisputable role for the diagnosis of meniscus and ligament injuries of the knee. Some technical advances have improved the diagnostic capabilities of magnetic resonance imaging so that diagnoses, which may change the therapeutic approach, such as a partial tear of the anterior cruciate ligament or confirmation of unstable meniscal injuries, are now made easier. This article describes the essential about magnetic resonance imaging technique and pathological results for the menisci, collateral ligaments and damage to the central pivot of the cruciate knee ligaments.


Subject(s)
Knee Injuries/diagnostic imaging , Ligaments, Articular/diagnostic imaging , Ligaments, Articular/injuries , Tibial Meniscus Injuries/diagnostic imaging , Contusions/diagnostic imaging , Humans , Ligaments, Articular/anatomy & histology , Magnetic Resonance Imaging , Menisci, Tibial/anatomy & histology , Rupture/diagnostic imaging , Tibial Meniscus Injuries/epidemiology
8.
Diagn Interv Imaging ; 97(7-8): 789-807, 2016.
Article in English | MEDLINE | ID: mdl-27118690

ABSTRACT

Fat is not just used by the body as bulk tissue. In addition to its role in storing energy and regulating hormone action, fat is used in some parts of the body for its mechanical properties. The anatomy of anterior knee fat is more complex than it appears at first sight and is capable of withstanding considerable compressive and shear stress. Specific lesions occur when such mechanical stress exceeds the physiological limits and are yet little known. Superficial fat can be the site of either acute injury by closed degloving called the Morel-Lavallée lesion or chronic injury, when subject to repeat excessive shear forces, due to more complex and less well-defined disruptions that result in pseudo-bursitis. There are three main anterior, intracapsular and extrasynovial fat pads in the knee joint, which are the infrapatellar fat pad (IFP) or Hoffa's fat pad, the quadriceps fat pad and the prefemoral fat pad. The IFP plays an important role as a mechanical shock absorber and guides the patella tendon and even the patella itself during flexion-extension movements. In response to repeated excessive stress, an inflammatory reaction and swelling of the IFP is first observed, followed by a fibrotic reaction with metaplastic transformation into fibrous, cartilaginous or bone tissue. More rarely, the two other deep fat pads (quadriceps and prefemoral) can, if subject to repeated stress, undergo similar restructuring inflammatory reactions with metaplasia resulting in tissue hardening, anterior pain and partial loss of function.


Subject(s)
Adipose Tissue/diagnostic imaging , Adipose Tissue/injuries , Knee Injuries/diagnostic imaging , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/injuries , Bursitis/diagnostic imaging , Friction/physiology , Humans , Knee Joint/anatomy & histology , Knee Joint/diagnostic imaging , Patellar Ligament/diagnostic imaging , Patellar Ligament/physiopathology , Sprains and Strains/diagnostic imaging , Synovitis/diagnostic imaging
9.
Diagn Interv Imaging ; 97(7-8): 779-88, 2016.
Article in English | MEDLINE | ID: mdl-27017094

ABSTRACT

The knee is one of the most studied anatomical structures by magnetic resonance imaging (MRI). Bone abnormalities are very frequently detected, whether or not related to the symptoms for which imaging was indicated. The aim of this pictorial study is to review the most commonly observed bone abnormalities of the knee, bearing in mind that the interpretation of MR images should always take into consideration both clinical and laboratory data, as well as the results of conventional X-ray imaging.


Subject(s)
Knee Joint/diagnostic imaging , Magnetic Resonance Imaging , Bone Neoplasms/diagnostic imaging , Cancellous Bone/diagnostic imaging , Cortical Bone/diagnostic imaging , Cortical Bone/injuries , Edema/diagnostic imaging , Edema/etiology , Fractures, Cartilage/complications , Fractures, Cartilage/diagnostic imaging , Humans , Knee Injuries/complications , Osteonecrosis/diagnostic imaging , Periosteum/diagnostic imaging , Reflex Sympathetic Dystrophy/complications
10.
Diagn Interv Imaging ; 96(12): 1279-92, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26564614

ABSTRACT

The flexor system of the fingers consisting of flexor tendons and finger pulleys is a key anatomic structure for the grasping function. Athletes and manual workers are particularly at risk for closed injuries of the flexor system: ruptured pulleys, ruptures of the flexor digitorum profundus from its distal attachment ("jersey finger"), and less frequently, ruptures of the flexor digitorum superficialis and of the lumbrical muscles. Open injuries vary more and their imaging features are more complex since tendons may be torn in several locations, the locations may be unusual, the injuries may be associated with nerve and vascular injuries, fibrosis… Sonography is the best imaging modality to associate with the clinical exam for it allows an experienced physician to make an accurate and early diagnosis, crucial to appropriate early treatment planning.


Subject(s)
Finger Injuries , Tendon Injuries , Diagnostic Imaging , Finger Injuries/diagnosis , Finger Injuries/surgery , Humans , Tendon Injuries/diagnosis , Tendon Injuries/surgery
11.
Diagn Interv Imaging ; 96(12): 1293-306, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26564616

ABSTRACT

The assessment of a swelling or mass of the wrist or the hand is commonly performed by radiologists. Because cysts on the wrist are, by far, the most frequent pathology. Diagnosis is usually based on standard radiography and ultrasound alone. Additional imaging techniques, and in particular MR imaging, are necessary to assess tumors, although malignant tumors of the hand are rare. Some benign cysts have pathognomonic characteristics visible on imaging. By understanding them, treatment planning may be improved.


Subject(s)
Hand , Neoplasms/diagnosis , Aged , Diagnostic Imaging , Epidermal Cyst/diagnosis , Humans , Magnetic Resonance Imaging , Male , Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Ultrasonography
12.
Transl Psychiatry ; 4: e437, 2014 Sep 09.
Article in English | MEDLINE | ID: mdl-25203168

ABSTRACT

Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.


Subject(s)
Depression/pathology , Depression/physiopathology , Disease Models, Animal , Emotions/physiology , Fatty Acids, Omega-3/physiology , Neurons/pathology , Neurons/physiology , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Animals , Depression/psychology , Dominance-Subordination , Hypothalamo-Hypophyseal System/pathology , Hypothalamo-Hypophyseal System/physiopathology , Male , Mice , Mice, Inbred C57BL , Pituitary-Adrenal System/pathology , Pituitary-Adrenal System/physiopathology , Receptors, Glucocorticoid/physiology , Signal Transduction/physiology
13.
Orthop Traumatol Surg Res ; 100(3): 317-21, 2014 May.
Article in English | MEDLINE | ID: mdl-24725906

ABSTRACT

PURPOSE: To evaluate diffusion MRI of the proximal femoral epiphysis and metaphysis as a prognosis factor in Legg Calvé Perthes (LCP) disease. METHODS: Thirty-one children (mean age 5.5 years, range 2.5-10.5) with unilateral LCP were included in a prospective, consecutive series. Radiographs were analysed and classified as per Herring criteriae. Mean follow-up was 19 months (range 6-30). Forty-nine MRI scans were performed at either the condensation or fragmentation stage. Apparent Diffusion Coefficient (ADC) of both the femoral epiphysis and metaphysis were measured bilaterally and ADC ratio were calculated, then compared to the Herring group. RESULTS: Sixteen hips were rated Herring A or B, 3 Herring B-C and 12 Herring C. ADC was increased in affected hips compared to unaffected sides, both at the femoral epiphysis (P<0.001) and metaphysis (P<0.0001). ADC ratio of the femoral metaphysis was positively correlated to Herring classification: if superior to 1.63, it was associated with a bad prognosis (Herring B-C or C) (P=0.0017, sensitivity=89%, specificity=58%). Interobserver reliability of ADC measurement was excellent. The 1.63 threshold could be determined as early as the condensation stage. CONCLUSIONS: Diffusion presents several advantages including being non radiating and non invasive. It does not need contrast medium administration and it can be performed without anaesthesia. The origin of the increased ADC remains unknown. Basically, it reflects molecular changes (true diffusion) but it is also influenced by the vascular supply (pseudo-diffusion). ADC ratio could provide an early prognosis before Herring classification is applicable. LEVEL OF EVIDENCE: Level III. Prospective uncontrolled study.


Subject(s)
Diffusion Magnetic Resonance Imaging , Early Diagnosis , Femur/pathology , Legg-Calve-Perthes Disease/diagnosis , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Prognosis , Prospective Studies , Reproducibility of Results
14.
Diagn Interv Imaging ; 95(3): 259-75, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24603038

ABSTRACT

Ultrasound examination of the brachial plexus, although at first sight difficult, is perfectly feasible with fairly rapid practical and theoretical training. The roots are accurately identified due to the shape (a single tubercle) of the transverse process of C7 in the paravertebral space, and the superficial position of C5 in the interscalene groove. The téléphérique technique allows the roots, trunks and cords to be followed easily into the supraclavicular fossa. In just a few years, ultrasound imaging of the plexus has become a routine anesthesia examination for guiding nerve blocks. In trained hands, it also provides information in thoracic outlet syndromes, traumatic conditions (particularly for postganglionic lesions) and tumoral diseases. Even if MRI remains the standard examination in these indications, ultrasound, with its higher definition and dynamic character, is an excellent additional method which is still under-exploited.


Subject(s)
Brachial Plexus/diagnostic imaging , Adult , Brachial Plexus/anatomy & histology , Brachial Plexus/injuries , Brachial Plexus Neuropathies/diagnostic imaging , Female , Humans , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Male , Peripheral Nervous System Neoplasms/diagnostic imaging , Reference Values , Spinal Nerve Roots/anatomy & histology , Spinal Nerve Roots/diagnostic imaging , Thoracic Outlet Syndrome , Tomography, X-Ray Computed , Ultrasonography, Doppler , Ultrasonography, Interventional , Young Adult
16.
Lung Cancer ; 80(3): 341-3, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23474129

ABSTRACT

BACKGROUND: Radiofrequency thermal ablation is an alternative option to manage primary or metastatic lung malignancies. It is particular useful for unresectable lesions because of the disease's location, prior resection, or comorbidities. Patients presenting with a lung tumor that occurs in a single lung due to a prior pneumonectomy are difficult to manage with a curative intent due to the risk of complications after local treatment. MATERIALS AND METHODS: We hereby report on treatment of a primary non-small-cell lung cancer in a previously contralateral pneumonectomised patient using per-cutaneous pulmonary radiofrequency thermal ablation. We also discuss literature that describes similar alternative minimally invasive procedures. CONCLUSION: Despite being a high-risk procedure, radiofrequency should be considered for patients with a single lung particularly when ineligible to surgery or stereotactic ablative radiation therapy. The procedure should be ideally associated with a pre-operative preventive chest tube.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Catheter Ablation/methods , Lung/physiopathology , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Male , Radiosurgery , Treatment Outcome
17.
Diagn Interv Imaging ; 94(1): 78-83, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23206418

ABSTRACT

PURPOSE: To evaluate diffusion MR imaging of the neck of the femur in Legg-Calve-Perthes disease (LCPD). MATERIAL AND METHODS: This is a prospective study in 27 children followed for unilateral LCPD. Forty-six MRIs were carried out with bilateral quantification of the apparent diffusion coefficient (ADC) of the neck of the femur. The intra- and inter-observer variability of the ADC measurements was evaluated. The association between the ADC and age as well as the healthy or pathological status of the neck of the femur and the Catterall classification were looked for. RESULTS: Intra- and inter-observer reproducibility of the ADC measurements was excellent. A statistically significant negative correlation between the ADC of the healthy neck of the femur and age was found. There was a significant increase in the ADC of the pathological neck of the femur compared to the healthy neck. The ratio of the pathological neck ADC and the healthy neck ADC was significantly associated with the Catterall classification. CONCLUSION: The quantification of the ADC of the neck of the femur is reproducible. This could be useful in the treatment of LCPD, where there is an early and significant increase in the ADC on the pathological side. This increase could have a prognostic value, as it is correlated with the Catterall classification.


Subject(s)
Diffusion Magnetic Resonance Imaging , Femur Neck/pathology , Legg-Calve-Perthes Disease/pathology , Child , Child, Preschool , Female , Humans , Male , Prospective Studies , Reproducibility of Results
18.
Orthop Traumatol Surg Res ; 99(1): 46-51, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23270721

ABSTRACT

INTRODUCTION: The reproducibility of various classification systems for trochanteric fractures is poor. This problem could be related to a lack of readability when using conventional X-rays. HYPOTHESIS: Computed tomography scanning (CT scan) will improve the interobserver reproducibility of the AO classification for trochanteric fractures. PATIENTS AND METHODS: This was a prospective, observational, descriptive study following a group of 53 patients with trochanteric fractures. The fractures were evaluated with conventional X-rays, CT scan slices and 3D reconstruction (3DR). The resulting images were blinded and analysed by two observers using two classification systems: AO and Evans modified by Jensen (EVJE). A sample size of 53 was needed to show an improvement in the interobserver reproducibility when deciding the AO classification type with CT scan images. Kappa coefficients were used to measure interobserver reproducibility and agreement; agreement is the degree of consistency in the analysis by one observer who views the same fracture on two different imaging modalities. RESULTS: The interobserver reproducibility for the AO classification was 0.28 for X-rays, 0.33 for CT scan and 0.28 for 3DR. For the EVJE classification, these coefficients were 0.50 for X-rays, 0.35 for CT scan and 0.47 for 3DR. The agreement rate between the two imaging modalities was between 0.38 and 0.58 for X-rays/CT scan and between 0.79 and 0.86 for CT scan/3DR. DISCUSSION: The primary objective of this study was not achieved. CT imaging does not improve the interobserver reproducibility of various classification systems for trochanteric fractures. However, by providing images as slices, the complex nature of fractures in this area was revealed. The challenges related to classifying various fractures are not exclusively related to a "readability" problem, but also an understanding and analysis problem. LEVEL OF EVIDENCE: Prospective diagnostic study, level III.


Subject(s)
Hip Fractures/classification , Hip Fractures/diagnostic imaging , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Female , Humans , Male , Observer Variation , Prospective Studies , Reproducibility of Results
19.
Diagn Interv Imaging ; 93(6): 520-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22677300

ABSTRACT

Infectious spondylodiscitis is an infection of the intervertebral disc and the adjacent vertebral bodies due to the introduction of a pyogen, usually by the haematogenous route. Plain film radiography (which is usually normal in the early stages) shows blurring of the vertebral endplates and a loss of disc height that progresses quickly. MRI is the examination of choice, as it detects oedema within the trabecular bone very early, before the onset of destruction. Injection of a contrast medium with fat signal saturation improves detection and visualisation of the spread of infection in the soft tissue and epidural space. Imaging can also be used to guide a needle aspiration to investigate the infective agent.


Subject(s)
Aspergillosis/diagnosis , Bacterial Infections/diagnosis , Candidiasis/diagnosis , Diagnostic Imaging , Discitis/diagnosis , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Contrast Media/administration & dosage , Female , Humans , Image Enhancement , Infant , Male , Middle Aged , Sensitivity and Specificity , Young Adult
20.
Mol Psychiatry ; 17(1): 71-84, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21606927

ABSTRACT

Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies.


Subject(s)
Actins/metabolism , Carrier Proteins/genetics , Dendrites/ultrastructure , Dendritic Spines/genetics , Mutation/genetics , Neurons/cytology , Animals , Autistic Disorder/genetics , Cell Line, Transformed/cytology , Cells, Cultured , Chlorocebus aethiops , Dendrites/genetics , Dendritic Spines/physiology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hippocampus/cytology , Humans , Microscopy, Confocal , Nerve Tissue Proteins , Transfection , Tubulin/metabolism
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