Michele Fornaro, MD (born Oct 9th, 1977) graduated in 2002 from the University of Genova, Genoa, Italy, and completed his residency program in 2008. In 2007-2008 MF completed a one-year "research fellowship" program at the Depression and Clinical Research Program (DCRP) at the Massachusetts General Hospital (MGH) - Harvard University -, Boston, MA, USA, under the supervision of Prof. Fava and Director Prof. Rosenbaum (http://www2.massgeneral.org/allpsych/depression/staff/previous-staff.html). Then, MF joined the bipolar clinical and research group headed by Prof. Giulio Perugi, MD at the Santa Chiara Hospital, University of Pisa, Pisa, Italy (2008-2011/ongoing research collaboration), while still completing his Doctorate in Applied Neurosciences from the University of Genova (2008-2011). On September 2011, MF was assigned the title of "Assistant Professor" at the University of Catania, Catania, Italy, as a teaching faculty member. MF was also awarded first prize at the annual poster-presentation event on "clinical psychopharmacology of mood and anxious disorders" endorsed by the European College of Neuropsychopharmacology (ECNP), held in Cascais, Portugal, on October 2011. On December 2011, MF began his "visiting scholarship" program at the Veterans Hospital (VA) at the University of California San Diego (USCD), La Jolla, San Diego, CA, USA, under the supervision of Prof. Kelsoe (former Director, Prof. Akiskal). There, he was introduced to CDKN1A (cyclin-dependent kinase inhibitor 1A (p21, Cip1)) gene functioning and its putative mediating role between bipolar disorders, circadian rhythms and lithium therapeutic response, while still attending to his primary clinical and research interests focusing on the epidemiology of Bipolar Disorder, Cyclothymia and their affective temperamental substrates, as well as on clinical psychopharmacology of Mood and Anxiety Disorders MF essentially developed while in touch with the one he considers his mentor, Prof. Perugi, MD.
Abstract: The relationship between anxiety and impulsivity is controversial and not well explored. The present investigation aims to compare impulsivity, measured by different rating tools, in patients with anxiety disorders vs. healthy controls. Forty-seven subjects with different anxiety disorders and 45 matched controls underwent diagnostic and symptomatological evaluations by the Mini Neuropsychiatric Interview (M.I.N.I) Plus 5.0; Bech-Raphaelsen Depression and Mania Scale (BRDMS), State-Trait Anxiety Inventory (STAI), Hypomania Check List (HCL-32) and the Clinical Global Impression (CGI); temperamental evaluations by the Questionnaire for the Affective and Anxious Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Modified (TEMPS-M), the Separation Anxiety Sensitivity Index (SASI), the Interpersonal Sensitivity Symptoms Inventory (ISSI); and psychometric and a neurocognitive evaluations of impulsivity using the Barratt Impulsiveness Scale (BIS-11) and the Immediate and Delayed Memory Task (IMT\DMT). Subjects with anxiety disorders were more impulsive than the controls in all the explored measures reporting higher scores in symptomatological and, temperamental scales. Patients with anxiety disorders without lifetime comorbidity with major mood episodes had greater trait and state impulsivity than controls. Further investigations are needed to assess whereas impulsivity might or might not be directly related to the anxiety disorder.
Abstract: Catatonic patients often experience prolonged inactivity and dehydration, thus being prone to venous stasis leading to life-threatening thrombosis and pulmonary embolism (PE). When this occurs, the prescription of electroconvulsive therapy (ECT), actually irreplaceable in most life-threatening cases, remains controversial essentially due to an increased risk for PE and cerebral haemorrhage, with timing clinical decisions being as crucial as difficult to take. We report the case of a catatonic patient affected by malnutrition, deep venous thrombosis, severe pressure ulcers and septic syndrome resulting from previous untimely management, successfully treated with 16 well-tolerated ECT applications upon intensive supportive care. Although anecdotal, cases like this remind the relevance of early ECT to reduce the risk for potentially life-threatening complications due to prolonged catatonic inactivity, especially to those clinicians substantially disregarding this practice.
Abstract: Introduction: Despite the clinical and social relevance of depression, and the availability of numerous antidepressants and non-pharmacological interventions, response rates remain unsatisfactory and novel therapeutic targets are being explored. Areas covered: This review starts with a brief overview of the evolution of the current antidepressant drug scenario and ends with a focus on the potential influence of the underestimation of bipolarity on the exploration of novel antidepressant drugs. Expert opinion: The field of antidepressant drug development has suffered from a relative decline recently and, with the exception of agomelatine, innovative non-monoaminergic antidepressants have yet to be developed. The need for more effective compounds is evident. Clinicians and researchers should pay greater attention to the impact of bipolarity in depression. The ultimate goal of this review is not to discourage the use of antidepressants but rather to encourage judicious prescriptions, and also to solicit a better collaboration between clinicians and preclinical researchers so that more reliable diagnostic criteria can be adopted.
Abstract: INTRODUCTION: Despite intense research efforts, still too little is known about the biological determinants of depression, thus soliciting diverse study approaches. Among others, the electroretinography (ERG) has been proposed even as a putative proxy (retinal) measurement of central dopaminergic activity for Major Depressive Disorder (MDD) both in drug-naïve patients and subjects receiving antidepressant treatments. Nonetheless, current evidences are merely preliminary, essentially considering just older classes of antidepressants, thus requiring confirmation studies even with newer agents as duloxetine. METHOD: Twenty MDD subjects and 20 matched controls received duloxetine 60mg/day for 12weeks, being monitored both by standard ERG recording and by administration of the Hamilton scales for Depression and Anxiety and the Young Mania Rating Scale at baseline and week 12 (end of the study). RESULTS: ERG mean rod b-wave amplitude significantly reduced from baseline to week 12 in those depressed subjects achieving final response (p=.024), decreasing from the highest rank values to the ones, substantially unmodified, seen among non-responders and controls. LIMITATIONS: Small sample size and lack of multiple assessments. CONCLUSIONS: At least some MDD patients responding to duloxetine might exhibit a peculiar ERG pattern, hypothetically indicating a specific biological background. If confirmed by larger-sampled studies, these results might shed further light in the understanding of the biological determinants of different subtypes of depression, ideally showing alternative patters of response upon different treatment interventions.
Abstract: Self-injurious behavior (SIB) associated with Tourette's syndrome (TS) is a severe neuropsychiatric condition that causes significant distress and can impair social functioning. The current treatment options for the condition include pharmacological, physical and psychosocial interventions. However, given the need for more effective interventions, especially for those patients who are unresponsive and/or intolerant to standard medications, further exploration of novel treatments is imperative. In this report, we present a case of SIB-TS that was successfully treated with pregabalin. The patient received 1-year of follow-up and was noted to have considerable improvement in symptoms. Although rigorous controlled studies are required, based on our case study, pregabalin may be a potential treatment option in some cases of SIB with TS.
Abstract: ABSTRACT: BACKGROUND: Despite multiple antidepressant options, major depressive disorder (MDD) still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide. METHODS: A total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24) augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score [greater than or equal to]50% vs baseline defined 'non-response'), the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale. RESULTS: At week 12, 15 patients out of 39 (38.5%) were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3%) had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001), while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 +/- 12.14 kg; P = 0.001) independently of the outcome. CONCLUSIONS: Although only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.
Abstract: The sequential endoproteolytic cleavages operated by the γ-secretase and the β-secretase (BACE1) on the amyloid-β protein precursor (AβPP) result in the production of the amyloid-β (Aβ) species, with two C-terminal variants, at residue 40 or at residue 42. Accumulation in brain tissue of small, soluble aggregates of Aβ42 is the major pathogenic event of Alzheimer's disease (AD). However, the physiologic activity of Aβ peptides is still elusive. Here, we show that expression of BACE1 is regulated by Aβ42, which augments BACE1 gene transcription through the JNK/c-jun signaling pathway. Of note, Aβ40 has much less effect on BACE1 expression. These findings unveil a positive feedback loop in which γ-secretase cleavage of AβPP releases a functionally-active peptide, Aβ42, that promotes BACE1 transcription. Thus, gene expression induced by Aβ42 may have implications in the neuronal dysfunction and degeneration that occurs in AD.
Abstract: The relationship between anxiety and impulsivity is controversial and not well explored. In a previous study we compared impulsivity, measured by different rating tools, in patients with anxiety disorders vs. healthy controls. In the same sample we now explore the influence of comorbid soft bipolar spectrum disorders on the relationship between anxiety disorders and impulsivity.
Abstract: The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.
Abstract: Catatonic syndromes involve a complex mixture of motor, behavioral, and systemic manifestations that are derived from unclear mechanisms. What is clear is that neurotransmitters, such as dopamine (DA), gamma-aminobutyric acid (GABA), and glutamate (GLU), are of major importance in the pathogenesis of catatonia and Neuroleptic Malignant Syndrome (NMS) and that serotonin (5-hydroxytryptamine [5-HT]) is crucial to the development of Serotonin Syndrome (SS). As medications with potent effects on modulation of monoamines proliferate, the diagnosis and management of these complex disorders become even more important. Without question, these syndromes have signs, symptoms and treatments that overlap, thus, considering the symptomatological load and the associated clinical burden (including potentially life-threatening conditions), the need for a better knowledge of the hypothesized biological mechanisms and pharmacological management is imperative. Although the search for a unique, conclusive approach to the management of catatonia is futile, stating the heterogeneity of the clinical pictures and the wide range of effective treatment choices (including non-pharmacological interventions), clinicians should not disregard an accurate, critical therapeutic approach to such a relevant, yet often disregarded, topic. The aim of this narrative review is to provide both clinicians and pharmacologists with a narrative, panoramic review on catatonia and associated clinical pictures, focusing on its general pharmacological management.
Abstract: To assess the prevalence and distribution of medically unexplained painful somatic symptoms (PSSs) versus nonpainful somatic symptoms (NPSSs) in patients diagnosed with major depressive episode (MDE).
Abstract: Immune modifications, including changes in interleukin (IL)-6 levels, have often been observed in major depressive disorder (MDD) during treatment with selective serotonin reuptake inhibitors (SSRIs) or the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine. Nevertheless, no equivalent observation for the SNRI duloxetine has been made to date.
Abstract: To evaluate the impact of Eating Disorders (EDs) lifetime co-morbidity among female with Bipolar Disorders (BDs) and to compare clinical and cognitive features among EDs subgroups.
Abstract: To evaluate the impact of Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV)-defined premenstrual dysphoric disorder (PMDD) lifetime co-morbidity among 92 bipolar patients.
Abstract: ABSTRACT: Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea.
Abstract: Mental Retardation (MR) is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD) and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over) prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for "agitated" TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.
Abstract: Isotretinoin, a drug used for moderate to severe acne, has been repeatedly associated with various psychiatric complications, although a definitive causal relationship has not been established to date. This case report describes a 25-year-old male who developed obsessive-compulsive disorder at the age of 23 years following isotretinoin treatment for acne (10-20 mg/day) since the age of 16 years. Although standard treatment for obsessive-compulsive disorder caused mood swings, the combination of fluvoxamine 300 mg/day and olanzapine 15 mg/day significantly improves the clinical picture. Although rare, severe adulthood psychiatric complications may occur following isotretinoin treatment, requiring management which is individually tailored to the patient.
Abstract: The activity of the β-secretase involved in the cleavage of amyloid-β (Aβ) is increased in sporadic late-onset Alzheimer's disease (AD). Whether the corresponding γ-secretase activity is altered is still uncertain. We evaluated mRNA expression and protein levels of presenilin 1 (PS1) and γ-secretase activity in the frontal cortex of 32 cases with late-onset sporadic AD and those of 29 control subjects. We found a significant increase in PS1 mRNA, protein levels and γ-secretase activity in AD cases. These findings suggest that upregulation of PS1 leads to Aβ overproduction and accumulation in sporadic AD.
Abstract: Treatment-Resistant Depression (TRD) represents a source of ongoing clinical and nosological controversy and confusion. While no univocal consensus on its definition and specific correlation with major mood disorders has been reached to date, a progressively greater number of evidences tend to suggest a revision of current clinical nosology. Since a better assessment of TRD should be considered mandatory in order to achieve the most appropriate clinical management, this narrative review aims to briefly present current most accepted definitions of the phenomenon, speculating on its putative bipolar diathesis for some of the cases originally assessed as unipolar depression.
Abstract: To determine the prevalence of major depressive disorder (MDD) and other selected axis-I disorders among women with newly diagnosed, untreated endocrine disorders.
Abstract: Subjective tinnitus is a frequent, impairing condition, which may also cause neurotransmitter imbalance at the cochlea. Psychopharmacologic agents, although not being the first-line treatment for tinnitus, may modulate cochlear neurotransmission, thereby influencing the subjective tinnitus experience.
Abstract: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes. METHOD:: Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile. RESULTS:: Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6. LIMITATION:: No blind evaluation and uncertain validity of personality inventory. CONCLUSION:: Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.
Abstract: The origins of Western culture extensively relate to Ancient Greek culture. While many ancient cultures have contributed to our current knowledge about medicine and the origins of psychiatry, the Ancient Greeks were among the best observers of feelings and moods patients expressed towards medicine and toward what today is referred to as 'psychopathology'. Myths and religious references were used to explain what was otherwise impossible to understand or be easily communicated. Most ancient myths focus on ambiguous feelings patients may have had towards drugs, especially psychotropic ones. Interestingly, such prejudices are common even today. Recalling ancient findings and descriptions made using myths could represent a valuable knowledge base for modern physicians, especially for psychiatrists and their patients, with the aim of better understanding each other and therefore achieving a better clinical outcome. This paper explores many human aspects and feelings towards doctors and their cures, referring to ancient myths and focusing on the perception of mental illness.
Abstract: While many ancient cultures contributed to our current knowledge about medicine and psychiatry origins, Ancient Greeks were among the best observers of feelings and moods patients could express toward medicine and toward what today referred as "psychopathology". Myths and religious references were used to explain what elsewhere impossible to understand or easily communicated. Most of ancient myths focus on ambiguous feelings patients could have towards drugs, especially psychotropic ones. Interestingly, such prejudices are common yet today. Recalling ancient findings and descriptions made using myths, should represent a valuable knowledge for modern physicians, especially for psychiatrists, and their patients, with the aim of better understanding each other and therefore achieving a better clinical outcome. The paper explores many human aspects and feelings toward doctors and their cures, referring to ancient myths, focusing on the perception of mental illness.
Abstract: Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease (AD). We measured plasma levels of amyloid-beta40 (Abeta40) and Abeta42 in 191 subjects with aMCI. Seventy-nine of them were clinically followed for two years. In the total cohort of aMCI cases, the average level of Abeta42, as well as the Abeta42/Abeta40 ratio, was significantly higher than those of the 102 cognitively normal age-matched subjects. The aMCI cases that converted to probable AD within 2 years had higher levels of Abeta42 and, to a lesser extent, Abeta40 than the stable cases. However the large variability of measured values indicates that plasma Abeta is not a suitable marker of incipient AD.
Abstract: Our aim was to present a comprehensive, updated survey on obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders (OCRDs) and their clinical management via literature review, critical analysis and synthesis. Information on OCD and OCRD current nosography, clinical phenomenology and etiology, may lead to a better comprehension of their management. Clinicians should become familiar with the broad spectrum of OCD disorders, since it is a pivotal issue in current clinical psychiatry.
Abstract: The density of the serotonin transporter in the plasma membranes of blood platelets was evaluated by labelled paroxetine binding in three different groups. These groups were: normal controls, epileptic patients having undergone a recent seizure (less than 4 days before) and patients who equally recently presented psychogenic non-epileptic seizures (pseudoseizures). Real seizures resulted in a significant decrease of membrane serotonin transporter density. In the instances of pseudoseizures, its membrane density was undistinguishable from that of normal controls. These data lend further support to the idea that down regulation of serotonin transporter may play a homeostatic role in the cessation of epileptic seizures.
Abstract: Obsessive-compulsive disorder is associated with a relevant impairment in social and interpersonal functioning and severe disability. This seems to be particularly true for the poor insight subtype, characterised by a lack of consciousness of illness and, consequently, compliance with treatment. Poor responsiveness to serotonergic drugs in poor insight obsessive-compulsive patients may also require an augmentation therapy with atypical antipsychotics.
Abstract: A case of subclavian-axillary vein thrombosis prompted us to review the recent literature on the subject. Paget-Shroetter disease is an uncommon disease, which is still associated with high early and late morbidity rates and the prevention of which requires early diagnosis and treatment. The importance of trauma (in the form of physical strain) in determining the symptoms of the disease is universally accepted. We observed subclavian-axillary vein thrombosis in a young 22-year-old athlete who complained of unexpected onset of pain in the left armpit, spreading to the arm and to the shoulder on the same side, functional impotence of the upper arm and swelling of the hand and forearm, and engorgement of the vessels in the arm, shoulder and clavipectoral region, which in the course of time developed the characteristics of a collateral circulation. The patient underwent phlebography which documented lack of opacification of the axillo-subclavian axis and showed the presence of a collateral circulation with dilation of the vein of the shoulder and arm. We first attempted to dissolve the thrombus by locoregional infusion of urochinase and later started anticoagulative therapy with an intravenous infusion of heparin (10,000 IU/h after a bolus of 500 units). Because of the poor result of thrombolysis and anticoagulative therapy and the progressive worsening of the disease, the patient underwent surgery to restore the continuity of the venous axis. The surgical procedure was performed through a skin incision along the upper edge of the collar-bone. This was dissected and the two stumps were well separated to allow a clear view of the subclavian vein. Phlebotomy, thrombectomy and reconstruction of the venous axis with an expanded polytetrafluoroethylene patch were performed. The postoperative course was uneventful and the patient underwent phlebography again on postoperative day 8, which demonstrated complete patency of the subclavian vein, and was discharged on postoperative day 20 on oral anticoagulative therapy.
