Turning visual shapes into sounds: early stages of reading acquisition revealed in the ventral occipitotemporal cortex.

The exact role of the left ventral occipitotemporal cortex (VOTC) during the initial stages of reading acquisition is a hotly debated issue, especially regarding the comparative effect of learning on early stimulus-dependent vs. later task-dependent processes. We show that this controversy can be solved with high-temporal resolution intracerebral EEG recordings of the VOTC. We measured High-Frequency Activity (50-150 Hz) as a proxy of population-level spiking activity while participants learned Japanese Katakana symbols, and found that learning primarily affects top-down/task-dependent neural processing, after a few minutes only. In contrast, adaptation of early bottom-up/stimulus-dependent processing takes several days to adapt and provides the basis for fluent reading. Such evidence that two consecutive stages of neural processing, stimulus- and task-dependent are differentially affected by learning, can reconcile seemingly opposite hypotheses on the role of the VOTC during reading acquisition.

Outcome of unstable isolated fractures of the posterior acetabular wall associated with hip dislocation.

BACKGROUND: Traumatic hip dislocation with fracture of the posterior acetabular wall is associated with high rates of residual invalidity. METHODS: The records of patients who underwent surgical treatment of traumatic dislocation of the hip associated with an isolated fracture of the posterior acetabular wall from 1999 to 2009 were reviewed. There were 30 men and 12 women, who at the time of the trauma had a mean age of 42 years (range 21-65). Mean follow-up duration was 5 years (range 2-10). Pre-operative fracture evaluation was based on the classification of Judet et al. which divided this fractures into three types: type 1 is characterized by a single fracture line separating a single bone fragment from the remaining part of the posterior wall; type 2 fracture involves several fragments of the posterior wall and in type 3, a type 1 or type 2 fracture is associated with a sunk cancellous area in the acetabular wall medial to the fracture line but not affected by it, due to the shear impact of the femoral head at the time of dislocation. Clinical evaluation of the outcome was according to the criteria of Merle D'Aubigné and Postel as modified by Matta. Outcomes were divided into excellent/good and fair/poor. Since treatment was standard, data were further analyzed to assess the relative importance of age, sex, follow-up duration, sciatic nerve lesion on admission and mechanism of injury, using the Chi-square test. RESULTS: Full clinical recovery without sequelae or radiographic abnormalities was achieved by 10 patients, 8 with type 1 fracture and 2 with type 2 fracture. A good outcome was seen in 13 patients, 3 with type 1 fracture, 9 with type 2 fracture and 1 with type 3 fracture. Eight patients, 3 with type 2 fracture and 5 with type 3 fracture, had a fair outcome. Only follow-up ≥6 years influenced outcome significantly (p > 0.005). CONCLUSION: Our conclusions in light of our experience are that in type 1 lesions, anatomical reduction and stabilization achieve excellent outcomes, both clinical and radiographic; type 2 fractures pose greater prognostic problems because their outcome is determined by the success of the reduction and fixation of a multi-fragment fracture; finally, different considerations apply to type 3 fractures, which present varying degrees of comminution and an impacted acetabular surface: their outcome depends on the quality of the anatomical and morphological restoration of acetabular congruence.

Seizure outcome after epilepsy surgery in tuberous sclerosis complex: Results and analysis of predictors from a multicenter study.

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Clinical and pathological aspects of solitary spinal neurofibroma.

Four cases are described of solitary spinal neurofibroma, a rare tumour of the spinal cord or nerve roots. Computerised tomography provided an accurate topographical definition of the tumour. Magnetic resonance imaging showed an increased T2-weighted signal and multiple areas of decreased T1- and T2-weighted signals centrally. The MR signals matched the histological examination which showed hyperplastic interfascicular connective tissue, pleomorphic cells, and tightly packed nerve fibres compressed by the surrounding loose connective tissue. Electron microscopy showed three types of cell: Schwann cells, fibroblast-like cells, and mast cells. The histological findings suggests that solitary spinal neurofibroma is a distinct pathological entity which could be diagnosed preoperatively from the MR images.

Morphological changes in growth-plate cartilage in osteogenesis imperfecta.

We obtained specimens of growth-plate cartilage from four patients with osteogenesis imperfecta. Light microscopy showed structural changes in the tissue and morphological changes in chondrocytes and matrix, particularly in the hypertrophic zone. There were changes in the process of calcification in the primary mineralisation zone of the cartilage. We also found histochemical changes in the matrix glycosaminoglycans (GAGs) in the zones where physiological mineralisation was disturbed and where the trabeculae were interrupted and poorly mineralised. In addition to the known molecular defects in collagen, changes in GAGs and non-collagenous proteins are important factors in the pathogenesis of the disease.

Antenatal diagnosis and obstetric management of Dandy-Walker syndrome.

Real-time ultrasound equipment has the potential for investigating the fetal neural axis and allows the diagnosis of many anomalies arising from this area. Five cases of Dandy-Walker syndrome, one of the major causes of congenital hydrocephalus, were diagnosed antenatally. In all cases ultrasound allowed specific recognition of the defect in the cerebellar vermis. This defect connected the fourth ventricle to a posterior fossa cyst in four cases and to an occipital meningocele in one case. In three cases the diagnosis was made prior to viability, and the parents elected termination of pregnancy. In two cases recognized in the third trimester, neurosurgical care was provided soon after delivery.

Subungual exostosis of the foot.

Eleven subungual exostoses of the foot (10 on the hallux, 1 on the third toe) were studied. The initial symptom was subungual pain. When a subungual mass of fibrous tissue appeared, the nail was pushed up and in one case the mass became infected. X-rays exhibited a bone mass protruding from the terminal phalanx on the dorsomedial aspect of the toe in all cases. All patients underwent surgical excision of the lesions with partial onychectomy. Three layers were identified in five cases: a cap of fibrous tissue, a middle zone of hyaline cartilage with enchondral ossification, and a deep zone of cancellous bone. In three other cases, the histological pattern was pleomorphic and poorly characterized. The study shows that most subungual bone masses exhibited the pathological features of conventional osteochondromas. Nonetheless, a small number of lesions were pleomorphic and differed from osteochondromas, with abundant fibrous tissue merging irregularly into scattered islets of cartilage that was not organized in columns. Radical excision of the mass achieved complete relief of symptoms and recovery without recurrences in all cases.

Anatomy of the Lisfranc joint complex.

The authors studied the Lisfranc joint complex using gross dissection and examination of anatomical sections of frozen samples in the frontal and sagittal planes. They distinguished a medial compartment, a central compartment, a lateral compartment, the secondary joint line, and the connections with the cuneoscaphoid articulation. The ligaments were divided on the basis of topography (dorsal, interosseous, and plantar) and course (longitudinal, oblique, and transverse). The dorsal and plantar ligaments reinforce the articular capsules. The interosseous ligaments are the strongest. A common characteristic of these ligaments is that they vary considerably in course, number, and insertions.

Plantar fibromatosis: an immunohistochemical and ultrastructural study.

The analogies between plantar fibromatosis and Dupuytren's disease (palmar fibromatosis) are well known. The latter is clinically more frequent and has been the object of extensive immunohistochemical and ultrastructural studies, with a view to investigating its pathogenesis. By contrast, such data on plantar fibromatosis are quite scarce. A histochemical, immunohistochemical, and ultrastructural study was performed on nodule tissue from six patients who were subjected to total fasciectomy for plantar fibromatosis. The study of myofibroblasts revealed features suggestive of their fibroblastic origin and evidenced a cytoskeleton and an extracellular filamentous system that could enable myofibroblasts to generate and exert the intracellular forces that contribute to the contraction of the aponeurosis. These aspects are similar to those observed in Dupuytren's disease and seem to lend support to the theory that the two diseases are expressions of the same disorder.

Polymethylmethacrylate-antiblastic drug compounds: an in vitro study assessing the cytotoxic effect in cancer cell lines--a new method for local chemotherapy of bone metastasis.

An in vitro study was performed assessing the pharmacologic properties of polymethylmethacrylate (PMMA)-antiblastic agent (doxorubicin and cisplatinum) mixtures in normal and neoplastic cell lines cultures. The study's aim was to analyze the polymerization capacity of PMMA in the presence of doxorubicin and cisplatinum, the release of drug from the mixture, the kinetics of release, and the effect of the released drugs in normal and neoplastic cell cultures. Our data show that even at high concentrations neither doxorubicin nor cisplatinum inhibit the polymerization of PMMA. Moreover, mixtures in vitro can release the antiblastic drug which maintains its pharmacologic activity on sensitive neoplastic cells. Therefore, the PMMA-antiblastic drug mixtures, along with current anti-cancer therapy (systemic chemotherapy and radiation therapy), may provide better local control of the metastatic lesion and of some bone tumors.

[Morton's disease: optic and electron microscopy observations]. / La maladie de Morton: observations en microscopie optique et électronique.

The authors performed an optic and electron-microscope investigation above the common digital nerve of the foot, whose fragments had been surgically removed from patients suffering from "Morton metatarsalgia" (neuroma). Histological sections were taken from pre-stenotic swelling in patients with clinical symptoms persisting for one year; perineural thickening without evidence of fibroblastic proliferation could be demonstrated, together with an intraneural deposition of an amorphous substance. In other patients suffering from Morton's disease for a longer time, a more pronounced epineural thickening in the pre-stenotic zone could be shown, with partial replacement of nerve fibers by amorphous substance. In the same patients endoneural fibrositis was seen at the level of the stenosis. Electron-microscopy in patients after one year showed an increase in collagenous endoneural fibers and microfibrils. These histopathological findings suggest a compressive mechanism in the pathogenesis of the damage to the common interdigital nerve in Morton's disease, caused by the extrinsic anatomical structures surrounding the nerve. The so-called "neuroma" can be identified with the pre-stenotic swelling.

[Heyman's operation for the treatment of congenital metatarsus varus]. / L'opération de Heyman pour le traitement du metatarsus varus congénital.

The authors report their experience with the operation of Heyman, i.e. complete release of the tarsometatarsal and intermetatarsal joint for the treatment of congenital metatarsus varus. This operation of Heyman is capable of meeting the requirements of correction if the indications are precise and if the surgical technique is perfect. The operation is indicated in cases of varus over 15 degrees, passively reducible, with good axes of the hindfoot and without bony alterations of the Lisfranc joint, in children between 3 and 8 years old. There should be a dorsal and medial capsulotomy, with section of the medial 2/3 of the plantar aspects of tarsometatarsal and intermetatarsal capsules; the lateral portion, the lateral 1/3 of the capsule and the insertions of the fibularis brevis and tibialis anticus should be spared. A complete capsulotomy is not indicated owing to the risk of dislocation of the tarsometatarsal joint. The correction should be stabilized during the operation by Kirschner wires to avoid a loss of correction when putting the foot in plaster.

The role of instrumental diagnostic methods in the staging of Sudeck's disease.

Forty patients with Sudeck's atrophy were assessed in order to evaluate the diagnostic accuracy of x-ray, scintigraphy and telethermography in staging the 3 phases of the disease. The dynamic and early static phases of scintigraphy were the most sensitive and specific instrumental tests for detecting the early stage, whereas telethermography was fairly sensitive but not very specific. Radiographic examination was not sensitive in detecting slight changes in bone density, but it was the most reliable index for recognizing the transition to stage II of the disease. Moreover, it was possible to confirm that the late static phase of scintigraphy is the index which is best related to bone metabolism.

Involvement of the muscle-tendon junction in skeletal muscle atrophy: an ultrastructural study.

BACKGROUND: The muscle-tendon junction (MTJ) is a physiologically vital tissue interface and a highly specialized region in the muscle-tendon unit. It is the weakest point in the muscle-tendon unit, making it susceptible to strain injuries. Nonetheless, knowledge of the pathological changes affecting this region and of its response to the atrophy process is very limited. The aim of the study was to examine MTJ ultrastructural morphology in patients with different conditions that induce skeletal muscle atrophy and to attempt a grading of the atrophy process. MATERIALS AND METHODS: Fifteen patients undergoing amputation in the distal or proximal third of the lower leg due to chronic or acute conditions were divided into two groups. Specimens of gastrocnemius muscle collected at the time of surgery were analyzed by histology and electron microscopy. The contact between muscle and tendon was measured using a dedicated software that calculated semi-automatically the base (B) and perimeter (P) of muscle cell finger-like processes at the MTJ. RESULTS: Electron microscopy. The cells in the atrophic muscle of the chronic group were shallow and bulky. In the acute group, the myotendinous endings differed significantly in their structure from those of the chronic group. In atrophic muscle, the contact between muscle and tendon was reduced by quantitative and qualitative changes in the myotendinous endings. The B/P ratio allowed definition of three grades of myotendinous ending degeneration. DISCUSSION: It is unclear whether degenerative changes induced by immobilization in muscle and, specifically, the MTJ are temporary and reversible or permanent. CONCLUSIONS: This preliminary study suggested a classification of ultrastructural MTJ changes into grade 0, reflecting a quite normal MTJ; grade 1, an intermediate process that might lead to irreversible atrophy or to recovery, spontaneously or with drug therapy; and grade 2, irreversible process with complete structural alteration.

Clinical outcome of closed isolated subtalar dislocations.

INTRODUCTION: Subtalar dislocation (SD) is an uncommon injury accounting for 1-2% of all dislocations. It involves simultaneous disruption of the talocalcaneal and talonavicular joints, without involvement of the calcaneocuboid or tibiotalar joints or talar neck fracture. We present a retrospective study of pure medial and lateral SDs treated conservatively and discuss the pathogenesis, classification, prognostics and therapeutic aspects of SD. MATERIALS AND METHODS: Thirty patients, 24 men and 6 women (mean age 33 years; range 18-55) with closed isolated SD were treated conservatively and re-evaluated at 5-12 years. There were 20 medial and 10 lateral dislocations. All patients were managed with immediate closed reduction under general anaesthesia. Open dislocations and SDs associated with fractures were excluded. RESULTS: The mean AOFAS Ankle-Hindfoot score was 78.8. Seven patients (all with medial SDs) had an AOFAS score of 100; 14 patients (11 with medial and 3 with lateral SD) had a mean AOFAS score of 85; 6 patients (three with medial and three with lateral SD) had a mean AOFAS score of 65; and 3 patients (all with lateral SDs) had a mean AOFAS score of 28. The latter patients subsequently underwent subtalar fusion, with a fair outcome. The mean AOFAS scores of patients with lateral and medial SD were not significantly different (P = 0.05). CONCLUSION: Various factors adversely affect outcome, including type of dislocation (lateral/medial, open/closed), severity of the injury, associated fractures, length of immobilization. Management of closed isolated SD is by immediate conservative treatment in order to avoid or reduce the incidence of early soft-tissue and vascular complications and poor long-term outcomes due to post-traumatic arthritis, talus necrosis and subtalar joint stiffness. However, complications may still arise despite correct treatment.

Cost-effectiveness of cemented versus cementless total hip arthroplasty. A Markov decision analysis based on implant cost.

BACKGROUND: Probabilistic decision analysis is a means of reflecting the uncertainty parameter in models and of presenting it in a comprehensible manner to decision-makers. MATERIALS AND METHODS: A cost-effectiveness model was constructed to compare the cementless and cemented total hip prostheses implanted at our department in terms of lifetime costs and quality-adjusted life-years (QALY). Revision rates were obtained from the Orthopaedic Prosthesis Register of the Laboratory of Medical Technology, Istituti Ortopedici Rizzoli, Bologna, Italy. RESULTS: The risk of early revision (at 5 years of follow-up) for cementless and cemented prostheses was 1.6% and 1.4%, respectively, resulting in equal QALY for the two implant types. Analysis of mean cost and QALY indicated that use of either implant is not associated with cost savings. DISCUSSION: Management with cementless or cemented total hip prostheses in a theoretical cohort of 70-year-old patients with fracture of the femoral neck or arthritis involving the hip is not significantly different according to the probabilistic results from the model.