Daniel Levi

Istituto Clinico Humanitas IRCCS, Milano, Lombardy, Italy

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Publications (14)42.02 Total impact

  • Article: Treatment of Chronic Headache of Cervical Origin With Lipostructure: An Observational Study.
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    ABSTRACT: Objective.- To test feasibility, safety, and efficacy of local transplant of stromal fraction of adipose tissue in the treatment of chronic headaches of cervical origin. Background.- Chronic headaches of cervical origin (chronic cervicogenic headache and occipital neuralgia) are characterized by persistent pain due to the involvement of the great occipital nerve, with concurrent myofascial spasm and the consequent nerve entrapment within the trapezoid tunnel. Methods.- Tolerability and effectiveness of treatment of chronic cervicogenic headaches refractory to conventional therapies were evaluated in 24 patients. The visual analog scale of pain and the medication use diary were used in the 3 months preceding treatment; moreover, in order to verify the quality of life, patients are required to fill before surgery the Neck Pain Disability Index, the Headache Disability Index, migraine disability assessment scale questionnaire, and the short-form 12 standard v1 questionnaire. Follow-up examination was performed at 3 and 6 months. Results.- In 19 cases (79.2%), a good clinical response was recorded. At 6-month follow-up analysis, recurrence of occipital pain was recorded in 7 cases (29.2%); there is a significant reduction in disability and pain scores, and also a significant reduction of need for pharmacologic treatment and a fast return to previous work capacities. Conclusions.- The key point of our therapeutic strategy might be the regenerative role of stromal fraction of adipose tissue transplanted in the area of the occipital nerve entrapment; the results of the present study are encouraging both in terms of reduction of pain scores and in terms of quality of life improvement. The technique is minimally invasive, and no complications were recorded; indeed, the procedure seems to be safe and effective, and thus, a randomized study with larger follow-up and in a large series will be started.
    Headache The Journal of Head and Face Pain 10/2012; · 2.52 Impact Factor
  • Article: Rai is a new regulator of neural progenitor migration and glioblastoma invasion.
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    ABSTRACT: The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knockdown impairs progenitor migration to the olfactory bulb. Its expression is retained in GBM stem/progenitor cells where it exerts the same promigratory activity. Rai silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple-signaling pathways, yet it always leads to reduced expression of proinvasive genes.
    Stem Cells 02/2012; 30(5):817-32. · 7.78 Impact Factor
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    Article: Neurovascular compression of the greater occipital nerve: implications for migraine headaches.
    Plastic and reconstructive surgery 02/2012; 129(2):353e-354e. · 2.74 Impact Factor
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    Article: Five-year outcome of surgical treatment of migraine headaches.
    Plastic and reconstructive surgery 11/2011; 128(5):564e-565e; author reply 565e. · 2.74 Impact Factor
  • Article: Human glioblastoma tumours and neural cancer stem cells express the chemokine CX3CL1 and its receptor CX3CR1.
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    ABSTRACT: Human gliomas represent an unmet clinical challenge as nearly two-thirds of them are highly malignant lesions with fast progression, resistance to treatment and poor prognosis. The most severe form, the glioblastoma multiforme, is characterised by a marked and diffuse infiltration through the normal brain parenchyma. Given the multiple effects of chemokines on tumour progression, aim of this study was to analyse the expression of the chemokine CX3CL1 and of its specific receptor CX3CR1 in 36 human surgical glioma samples, with different degrees of histological malignancy and in glioblastoma-derived neurospheres. Herein we show that both ligand and receptor are expressed at the mRNA and protein levels in most specimens (31/36). While receptor expression was similarly detected in low or high grade tumours, the uppermost scores of CX3CL1 were found in grades III-IV tumours: oligodendrogliomas, anaplastic astrocytomas and glioblastomas. Accordingly, the expression of CX3CL1 was inversely correlated with patient overall survival (p = 0.01). Glioblastoma-derived neurospheres, containing a mixed population of stem and progenitor cells, were positive for both CX3CR1 and for the membrane-bound chemokine, which was further up-regulated and secreted after TNF-IFNγ stimulation. Confocal microscopy of 3D neurospheres showed that the ligand was primarily expressed in the outer layer cells, with points of co-localisation with CX3CR1, indicating that this ligand-receptor pair may have important intercellular adhesive functions. The high expression of CXC3L1 in the most severe forms of gliomas suggests the involvement of this chemokine and its receptor in the malignant behaviour of these tumours.
    European journal of cancer (Oxford, England: 1990) 12/2010; 46(18):3383-92. · 4.12 Impact Factor
  • Article: Vertebroplasty for pain relief and spinal stabilization in multiple myeloma.
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    ABSTRACT: Mechanical stabilization of oncological vertebral fractures with cement augmentation is the first mechanism of pain relief, with or without restoration of vertebral body height. The aim of this study was to assess the safety and efficacy of vertebroplasty for painful vertebral body fractures in patients with multiple myeloma, in each phase of the disease. The authors reviewed a consecutive group of patients with multiple myeloma who underwent vertebroplasty at our Institute between November 2003 and December 2005. Twenty-eight levels were performed on 11 patients during 14 treatment sessions. All patients suffered from intractable back pain, and presented various lesion types (with and without fractures of posterior wall, and with and without epidural disease). The preoperative median visual analog scale (VAS) score was 7. The median duration of symptoms was 1.1 months. Eight patients were ambulating with orthopaedic devices (57%) in the pre-treatment period. Improvement or complete pain relief was observed in all patients (immediately in 8 cases, and after 2 days in 6 cases). The median VAS pain score decreased to 2. There was no symptomatic procedure-related complication. There were three cases (21%) of PMMA leakage: in the disc space in one case (7%), and in the anterior spinal canal in two cases (14%). Complete removal of orthopaedic devices was obtained in five patients (36%). No new deformation or collapse of the treated vertebrae was observed during the follow-up (range 1 day-25 months). In conclusion, vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease. We also treated three and more levels in 28% of cases in a single session without complications. Due to the early pain relief and the low complication rate, it is possible to expand the indication to vertebroplasty for the prophylactic augmentation of those vertebral bodies at risk of fracture in which significant neoplastic substitution of the body is present.
    Neurological Sciences 04/2010; 31(2):151-7. · 1.32 Impact Factor
  • Article: Anatomical variations of the occipital nerves: implications for the treatment of chronic headaches.
    Plastic and reconstructive surgery 11/2009; 124(5):1727-8; author reply 1728. · 2.74 Impact Factor
  • Article: Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules.
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    ABSTRACT: The degenerative pathologies of the intervertebral disc have a remarkable social impact in the industrialized countries and can provide serious disabilities in the population. The current treatment consists of conservative treatments (such as symptomatic pharmacological therapies and physiokinetic therapy) and surgical treatments (intervertebral fusion, total disc replacement, nucleus pulposus (NP) replacement, or surgical exeresis). Recent advances in cell therapy foresee the possibility of regenerating the damaged disc; the autologous disc tissue can be withdrawn, in vitro regenerated, and re-implanted. The aim of this work was to verify whether autologous adipose-derived adult stem cells can improve the quality of an in vitro reconstructed nucleus pulposus tissue. A three-dimensional (3D) co-culture of NP cells and adipose tissue non-adipocyte fraction cells (nAFs) was assessed in a previously developed alginate 3D culture system following the good manufacturing practice guidelines to ensure patient safety for clinical studies. Morphological investigation of cultured and co-cultured cells was performed using transmission electron microscopy and immunofluorescence for collagen type I, aggrecan, CD90, CD34, and vimentin. Results indicate that co-culture of NP and nAFs improves the quality of the in vitro reconstructed tissue in term of extracellular matrix production and 3D cell organization. Technological resources are available for NP cell encapsulation intended for regenerating the intervertebral disc.
    Tissue Engineering Part A 08/2008; 14(8):1415-23. · 4.64 Impact Factor
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    Article: A role for the transcription factor HEY1 in glioblastoma.
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    ABSTRACT: Abstract Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically up-regulated in glioma and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1 may be a therapeutic target for glioblastoma patients. Moreover, HEY1 may represent a molecular marker to distinguish GBM patients with a longer survival prognosis from those at high risk.
    Journal of Cellular and Molecular Medicine 04/2008; 13(1):136-46. · 4.13 Impact Factor
  • Article: Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue.
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    ABSTRACT: It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two-dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non-Euclidean geometrical complexity of the two-dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space-filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues (P = 0.01), normal versus secreting adenomatous tissues (P = 0.0003), and normal versus non-secreting adenomatous tissues (P = 0.047), whereas the difference between the secreting and non-secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two-dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.
    Journal of Anatomy 12/2007; 211(5):673-80. · 2.37 Impact Factor
  • Article: The neuroanatomical plates of Guido da Vigevano.
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    ABSTRACT: Guido da Vigevano was an Italian physician and engineer who lived in the 13th and 14th centuries. He was the first scientist who used pictures to illustrate his anatomical descriptions, developing for the first time a close relationship between anatomical studies and artistic drawings. This was further developed in the Renaissance. In his textbook Anathomia are displayed six plates showing for the first time neuroanatomical structures and techniques: dissection of the head by means of trephination, and depictions of the meninges, cerebrum, and spinal cord. On the surface of the brain painting it is possible to recognize a vague patterning of cortical convolutions. Ventricles are also described and shown. This book constituted the first attempt in the history of neuroscience to illustrate an anatomical description with schematic pictures to achieve a better understanding of such complex structures.
    Neurosurgical FOCUS 02/2007; 23(1):E15. · 2.87 Impact Factor
  • Article: Spinal decompression and vertebroplasty in Paget's disease of the spine.
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    ABSTRACT: Paget's disease is an osteometabolic disorder affecting in particular long bones. The spine is the second most commonly involved site in Paget's disease. This pathology can cause low back pain, spinal stenosis, myeloradiculopathy, and vertebral collapse. Medical therapy is the first choice for the treatment of Paget's disease of the spine; in case of failure, surgery remains a valid option. In the present article, we report a case of a patient with leg disability due to myelopathy caused by spinal Paget's disease treated with spinal decompression and vertebroplasty. To our knowledge, this is the first case report in which these procedures have been performed together in the same operation to treat spinal pathologies due to Paget's disease.
    Surgical Neurology 09/2006; 66(2):189-91; discussion 191. · 1.67 Impact Factor
  • Article: Functional disability after instrumented stabilization in lumbar degenerative spondylolisthesis: a follow-up study.
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    ABSTRACT: Low back pain (LBP) is a widespread health problem and a major contributor to increasing health costs and lost work days. Different pathologies cause LBP and one of these is lumbar degenerative spondylolisthesis (SPL). There are no generally accepted and standardized methods for assessing the outcome of patients treated for degenerative lumbar SPL. This study aims to assess quality of life after surgery for lumbar degenerative SPL through the adoption of outcome measures. We studied 76 patients treated, for degenerative lumbar SPL, with spinal stabilization, decompression and bilateral dorsolateral fusion, followed up for at least two years. We used the Roland-Morris (RM) scale and the Oswestry Disability Index (ODI) to assess the quality of life of the patients before surgery and at follow up. Each patient was pre-operatively studied through standard and dynamic x-rays, CT scan and MRI of lumbar column. Relationships between clinical, radiological and disability scores, grouped by categories, were tested. The sample comprised 25 males and 51 females. Mean age was 59.6 years (SD 12.2). The mean duration of symptoms (from clinical onset to surgery) was 23.42 months (median 13, range 4-100 months). In about half of the cases, duration of symptoms before surgery was >12 months. At follow up, the fusion rate was 85.5%, and the ODI score was significantly reduced: an improvement of <20 points in 35.7% of patients, and of >20 points in 55.7%. On the RM scale, 59.4% of patients had a reduction >5 points, 13.1% a reduction of 2-4 points, and 27.5% an unchanged or worse score. There was no significant reduction in RM scale and ODI scores in patients with fusion versus pseudoarthrosis. Instrumental pedicle screw fixation and arthorodesis seem to be very effective in improving quality of life, as shown by the reduced disability scores at follow up.
    Functional neurology 21(1):31-7. · 1.52 Impact Factor
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    Article: Expression of the transcription factor HEY1 in glioblastoma: a preliminary clinical study.
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    ABSTRACT: The hairy/enhancer of split (E(spl))-related family of transcription factors (HES and HEY) are established targets of the notch signaling pathway, which has been implicated in different developmental processes, tumor formation and the self-renewal of neural stem cells. We determined the expression of HEY1 in human malignant gliomas to investigate whether its expression might be related to prognosis. The expression of HEY1 was studied by in situ hybridization on 62 cases of glioblastoma. Patients were treated with surgery followed by chemotherapy and radiotherapy. We considered as end points of the study the overall survival time and progression-free interval. Correlations between HEY1 expression and tumor grade/patient overall survival and free interval before recurrence were analyzed using univariate analysis. Based on the in situ hybridization results, HEY1 expression rate was reported as negative staining in 13 cases (20.6%), as weak staining in 11 cases (17.3%), as moderate staining in 21 cases (33.3%), and as strong staining in 17 cases. We considered in the analysis the cumulative expression of HEY1 at in situ hybridization (Hey Index) as negative in 13 cases and positive in 49 cases (77.78%). The overall survival (P = 0.002) and the free-interval (P = 0.012) were significantly longer in patients who were negative for HEY1 expression. Our data suggest that expression of HEY1 might be used as a marker to distinguish glioblastoma patients with a relatively good prognosis from those at high-risk, and that, in the future, HEY1 might represent a therapeutic target.
    Tumori 96(1):97-102. · 0.86 Impact Factor