Postoperative rehabilitation after simultaneous anterior cruciate ligament reconstruction and opening wedge high tibial osteotomy is a complex concept. Different osteotomy techniques, extremely selected patients, high expectations in returning to previous sport activities, and the different individual physical profile and performances make traditional chronological criteria impractical and unfeasible. This study presents a novel rehabilitation in which functional objective criteria are considered the key factors for standardizing a 4-step protocol. Each step is "individualized", based on the patient's response to the healing processes and to the different training phases, allowing for a safe return to sports competitions. This definitively implies a strict collaboration between patient, surgeon, physician and physiotherapists, as well as thorough and detailed patient education. Due to the high versatility of these new rehabilitation concepts, the application of the "individualized" steps described in this study may be broadened to include different sports medicine knee injuries that may benefit from a specific, detailed and carefully patient-centered rehabilitation project.

Periprosthetic osteolysis is still one of the major limitations of prosthetic joints longevity. The process of this "silent" iatrogenic disease involves both mechanical and biological factors that initiate a local immune response in the periprosthetic tissue that eventually lead to implant loosening and failure. There are many causes of the primary aseptic loosening inside the periprosthetic microenvironment, but the most important elements are the wear debris and the cell-particle interactions. Together with implant position, micromotion, bearings, joint fluid pressure, and increased load on the joints drive the pathogenesis of the disease. This narrative review aims to summarise recent studies describing the biological and mechanical factors in the pathogenesis of osteolysis and some of the current pharmacological attempts to "rescue" a failing implant.

13 morPhometrIC, geodetIC and geoPhYsICal surveYs of mud volCanoes: evIdenCe of teCtonIC Control In the sICIlIan CollIsIonal Belt G. De Guidi1, F. Carnemolla1, G. Barreca1, F. Brighenti1, C. Monaco1, A. Di Pietro1, S. Marchese1, D. Messina1, L. Scarfì2, A. Vecchio1 1 Dipartimento di Scienze Biologiche, Geologiche e Ambientali, Sezione di Scienze della Terra, Università di Catania, Italy 2 Istituto Nazionale di Geofisica e Vulcanologia, Osservatorio Etneo, Catania, Italy

2012; 27: 339–40. Cerasa A, Messina D, Pugliese P, Morelli M, Lanza P, Salsone M, et al. Increased prefrontal volume in PD with levodopa-induced dyskinesias: a voxel-based morphometry study. Mov Disord 2011; 26: 807–12. Cerasa A, Pugliese P, Messina D, Morelli M, Gioia MC, Salsone M, et al. Prefrontal alterations in Parkinson’s disease with levodopainduced dyskinesia during fMRI motor task. Mov Disord 2012; 27: 364–71. Cerasa A, Koch G, Donzuso G, et al. A network centred on the inferior frontal cortex is critically involved in levodopainduced dyskinesias. Brain 2015; 138: 414–27. Fahn S. The spectrum of levodopa-induced dyskinesias. Ann Neurol 2000, 47 (Suppl 1): 2–9. Gross RE, Lombardi WJ, Lang AE, Duff J, Hutchison WD, Saint-Cyr JA, et al. Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson’s disease. Brain 1999; 122: 405–16. Lees A, Tolosa E, Olanow CW. Four pioneers of L-dopa treatment: Arvid Carlsson, Oleh Hornykiewicz, George Cotzias and Melvin Yahr. Mov Disord 2015; 30: 3–6. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong MR, Olanow CW. Pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease: problems with the current model. Ann Neurol 2000, 47 (4 Suppl 1): 22–32. Page RD, Sambrook MA, Crossman AR. Thalamotomy for the alleviation of levodopa-induced dyskinesia: experimental studies in the 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine-treated parkinsonian monkey. Neuroscience 1993; 55: 147–65. Périer C, Tremblay L, Féger J, Hirsch EC. Behavioral consequences of bicuculline injection in the subthalamic nucleus and the zona incerta in rat. J Neurosci 2002; 22: 8711–19. Rascol O, Sabatini U, Brefel C, Fabre N, Rai S, Senard JM, et al. Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia. Brain 1998; 121: 527–33.

2011;77;1042-1047 Published Online before print August 10, 2011 Neurology M. Morelli, G. Arabia, F. Novellino, et al. A cohort study MRI measurements predict PSP in unclassifiable parkinsonisms: This information is current as of August 10, 2011 http://www.neurology.org/content/77/11/1042.full.html located on the World Wide Web at: The online version of this article, along with updated information and services, is

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. Relationships between immunohistochemical data and clinicopathological characteristics were investigated using the Chi-square test; the cohort was analysed with respect to pT1a and pT1b BC as well as to node status. Ductal infiltrating carcinoma was the prevalent histotype in the pT1a and pT1b stages; G2 was a more common tumour grade, with a range between 64.6% and 70% of pT1a and pT1b, respectively. Taking into consideration the lymph node involvement of pT1a,b BC. only 17.1% cases were node-positive without a relevant difference between pT1a and pT1b. No significant differences between pT1a and pT1b BC cases emerged in relation to Ki67 LI, hormone receptors and HER2 status. T1a,b BC cases were stratified by node involvement and a significant relationship was observed with grade as well as with HER2 status. A significant relationship for pT1a cases emerged only for tumour grade, while pT1b cases showed a significant correlation exclusively with HER2 status. Our data clearly support the operative guidelines of the National Comprehensive Cancer Network. Therefore, the combined treatment with trastuzumab plus chemotherapy should be administered only to patients with pT1b or larger BCs. In small HER2-positive pT1a or microinvasive BC, this therapy should be considered on a case-by-case basis, considering tumour grade as the first characteristic.

OBJECTIVE:Magnetic resonance parkinsonism index (MRPI) has been proposed as a powerful tool to discriminate patients with progressive supranuclear palsy (PSP) from those with Parkinson disease (PD) or other parkinsonisms, on an individual basis. We investigated the usefulness of MRPI in predicting the clinical evolution in PSP of patients with clinically unclassifiable parkinsonism (CUP), i.e., parkinsonism not fulfilling the established clinical diagnostic criteria for any parkinsonian disorders, using a cohort study.METHODS:Forty-five patients with CUP underwent baseline clinical evaluation and MRI with calculation of MRPI. All patients were divided in 2 groups according to MRPI values. A group included 30 patients with CUP with normal MRPI values while the other group included 15 patients with CUP with MRPI values suggestive of PSP (higher than 13.55). A clinical follow-up was performed in all patients.RESULTS:Duration of clinical follow-up in these 2 groups was 28.4 ± 11.7 months (mean ± SD). None of the patients with CUP with normal MRPI values fulfilled established clinical criteria for PSP (follow-up ranging from 24 to 60 months). By contrast, 11 of 15 patients with CUP with abnormal MRPI values (higher than 13.55) developed during the follow-up (range from 6 to 48 months) additional clinical features characteristic of probable (1 patient) or possible (10 patients) PSP. MRPI showed a higher accuracy in predicting PSP (92.9%) than clinical features, such as vertical ocular slowness or first-year falls (61.9% and 73.8%, respectively).CONCLUSIONS:Our findings suggest that MRPI is more powerful than clinical features in predicting the evolution of CUP toward PSP phenotypes.

Mutations in the gene DJ-1 have been shown to be a rare cause of early-onset Parkinson's disease (EOPD). Since DJ-1 mutations have been found in patients with Parkinson's disease (PD) from southern Italy, we aimed to investigate whether polymorphisms within the DJ-1 gene could represent a risk factor for sporadic PD. First, we genotyped 294 patients with PD and 298 controls coming from southern Italy to assess the distribution of the insertion/deletion (Ins/Del) polymorphism. In a second phase, we identified five single-nucleotide polymorphisms (SNPs) useful to delimit a region potentially involved and genotyped all patients and controls for these markers. All the markers analyzed were significantly associated with PD at both allelic and genotypic level. The most significant association with the disease was found at the Ins/Del polymorphism (p = 0.0001; adjusted odds ratio (OR ) = 2.05; confidence interval (CI ) = 1.36-3.08). When we considered a three-marker sliding window, we found a highly significant association between the disease and the haplotypes including markers rs17523802, Ins/Del, and rs3766606 (p = 0.0007) and markers Ins/Del, rs3766606 and rs7517357 (p = 0.0054). Our results indicate that polymorphisms located in a region spanning 3535 bp from the promoter to the intron 2 of the DJ-1 gene confer risk to sporadic PD in southern Italy.

BACKGROUND AND PURPOSE:Essential tremor (ET) is a slowly progressive disorder characterized by postural and kinetic tremors most commonly affecting the forearms and hands. Several lines of evidence from physiologic and neuroimaging studies point toward a major role of the cerebellum in this disease. Recently, voxel-based morphometry (VBM) has been proposed to quantify cerebellar atrophy in ET. However, VBM was not originally designed to study subcortical structures, and the complicated anatomy of the cerebellum may hamper the automatic processing of VBM. The aim of this study was to determine the efficacy and utility of using automated subcortical segmentation to identify atrophy of the cerebellum and other subcortical structures in patients with ET.MATERIALS AND METHODS:We used a recently developed automated volumetric method (FreeSurfer) to quantify subcortical atrophy in ET by comparing results obtained with this method with those provided by previous evidence. The study included T1-weighted MR images of 46 patients with ET grouped into those having arm ET (n = 27, a-ET) or head ET (n = 19, h-ET) and 28 healthy controls.RESULTS:Results revealed the expected reduction of cerebellar volume in patients with h-ET with respect to healthy controls after controlling for intracranial volume. No significant difference was detected in any other subcortical area.CONCLUSIONS:Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from a previous study based on VBM. The current findings extend the literature by providing initial validation for using fully automated segmentation to derive cerebellar volumetric information from patients with ET.

BACKGROUND AND PURPOSE:Our aim was to investigate the presence of brain gray matter (GM) abnormalities in patients with different forms of essential tremor (ET).MATERIALS AND METHODS:We used optimized voxel-based morphometry (VBM) and manually traced single region-of-interest analysis in 50 patients with familial ET and in 32 healthy subjects. Thirty patients with ET had tremor of the arms (a-ET), whereas the remaining 20 patients had both arm and head tremor (h-ET).RESULTS:VBM showed marked atrophy of the cerebellar vermis in the patients with h-ET with respect to healthy subjects (P(corrected) < .001). Patients with a-ET showed a trend toward a vermal GM volume loss that did not reach a significant difference with respect to healthy controls (P(uncorrected) < .01). The region-of-interest analysis showed a reduction of the cerebellar volume (CV) in the h-ET group (98.2 +/- 13.6 mm(3)) compared with healthy controls (110.5 +/- 15.5 mm(3), P < .012) as well as in the entire vermal area (790.3 +/- 94.5 mm(2), 898.6 +/- 170.6 mm(2), P < .04 in h-ET and control groups, respectively).CONCLUSIONS:Atrophy of the cerebellar vermis detected in patients with h-ET strongly supports the evidence for the involvement of the cerebellum in the pathophysiology of ET. The lack of a significant CV loss observed in patients with a-ET suggests that a-ET and h-ET might represent distinct subtypes of the same disease.

Previous MR studies have established that bilateral transverse sinus stenosis (BTSS) predicts idiopathic intracranial hypertension without papilledema (IIHWOP) in migraine. However, it is uncertain whether BTSS identifies IIHWOP in patients with chronic tension-type headache (CTTH): using cerebral MR venography this study aimed to address this question.In a prospective study from February 2002 to December 2006, 198 consecutive patients with CTTH underwent MR venography. Of these patients, 58 underwent lumbar puncture to measure cerebrospinal fluid (CSF) pressure. MR venography and lumbar puncture were also performed in 45 age-matched control subjects. BTSS was considered present when the signal flow was poor or lacking (flow gap) in the mid-lateral portion of both transverse sinuses. IIHWOP was diagnosed if the patient met the diagnostic criteria for idiopathic intracranial hypertension and did not have papilledema. Among the 198 patients with CTTH who underwent MR venography, 18 (9%) had BTSS. Thirteen of these 18 patients with BTSS underwent lumbar puncture, and nine (69.2%) had IIHWOP. CSF opening pressure was normal in all 45 patients as well as in all 45 controls with normal MR venography.These data suggest that BTSS on MR venography is associated with increased intracranial pressure in the absence of papilledema in patients with headache mimicking CTTH.

Background: The headache profile of patients with idiopathic intracranial hypertension without papilledema (IIHWOP) may be indistinguishable from that of migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in patients with migraine is unknown. Objective: To detect the frequency of BTSS in adult patients with migraine and to investigate whether the presence of BTSS identifies patients with IIHWOP. Methods: In a prospective study from December 2000 to November 2005, 724 consecutive patients with recurrent headaches who fulfilled International Headache Society diagnostic criteria for migraine underwent cerebral MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 70 age-matched control subjects. Results: Six hundred seventy-five of the 724 patients with migraines had normal MRV. Seventy of these 675 patients underwent LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724 patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF pressures within normal limits. CSF pressure was normal in both patients and controls with normal MRV. Conclusions: Of patients with migraine, 6.7% had bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic intracranial hypertension without papilledema (IIHWOP). These results suggest that patients with migraine who present bilateral transverse sinus stenosis on cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

BACKGROUNDSeveral factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD.OBJECTIVETo examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease.DESIGNCohort study.SETTINGReferral center for Parkinson disease in Calabria, southern Italy. Patients Two hundred fifty patients with Parkinson disease were screened for the presence or absence of PDD following a short-term levodopa administration, and 215 subjects were available for further evaluations, including genotypic analysis of the CA dinucleotide short tandem repeat (CAn-STR) polymorphism located in the dopamine receptor D2 gene (DRD2).RESULTSOne hundred five patients (48.8%) exhibited PDD following short-term levodopa administration, and 110 patients (51.2%) did not. Multivariate logistic regression analysis showed that independent predictors for the occurrence of PDD were female sex, earlier age at onset of Parkinson disease, longer duration of treatment, and higher dose of levodopa. Genetic factors related to the DRD2 CAn-STR polymorphism were not independent predictors for PDD in the total population, but they had a strong protective effect on the appearance of PDD when the multivariate analysis was performed in men (odds ratio, 0.34 [95% confidence interval, 0.14-0.84]). In women, a genetic protective effect on PDD was not evident.CONCLUSIONSRisk factors for PDD, both clinical and genetic, act in different ways for men and women. Genetic factors related to the DRD2 polymorphic status have a protective effect on PDD development in men but not in women. A female sex-related effect for the risk of PDD may be so strong that it overcomes any protective effect due to genetic factors.