The impact of SARS-CoV-2 pandemic on Oncologic and Degenerative Spine Surgery Department activity: the experience of Rizzoli Orthopaedic Institute under COVID-19 lockdown.

OBJECTIVE: Experience of Department of Oncologic and Degenerative Spine Surgery of Rizzoli Orthopaedic Institute during SARS-CoV-2 pandemic lockdown. PATIENTS AND METHODS: Retrospective observational study of surgically treated patients from 09th March 2020 to 04th May 2020. DATA COLLECTED: age, sex, type of disease, neurological status, days of hospitalization, complications and type of discharge. A comparison analysis with same period of the last year was performed in order to evaluate the impact of COVID-19 spreading on daily surgical activity. RESULTS: A total of 107 surgical procedures in 102 patients were performed from 09th March 2020 to 04th May 2020. Analysis showed a statistically significant difference in age, sex, ASIA class and type of treated disease compared to the same period of the last year (p=0.042, 0.006, 0.022 and 0.007, respectively). No statistically significant differences were observed in type of discharge, length of hospitalization and complications (p= 0.447, 0.261 and 0.127, respectively). 3 COVID-19 infections have been identified in hospitalized patients. 1 COVID-19 patient wad admitted from Emergency Department and was managed according to a dedicated path. CONCLUSIONS: Surgical activity was paradoxically increased during SARS-CoV-2 pandemic lockdown through the management of urgent and non-deferrable spinal disease with a low rate (3,9%) of COVID-19 infections.

Spinal tuberculosis: proposed spinal infection multidisciplinary management project (SIMP) flow chart revision.

OBJECTIVE: We propose a revised flow chart of spinal infection multidisciplinary management project (SIMP) aimed to standardize the diagnostic process and management of spinal tuberculosis (TB). MATERIALS AND METHODS: We reviewed data from all TB cases with osteoarticular involvement treated at a large tertiary teaching hospital in Bologna, Northern Italy, from January 2013 to December 2017. We cross-linked notified osteoarticular TB cases with SIMP database and we analysed clinical, diagnostic, and treatment data of all cases managed by SIMP. RESULTS: Osteoarticular TB accounted for the 7.8% (n=40) of all TB cases notified between 2013 and 2017 (N=513). Among the identified cases, 52% (n=21/40) had spine involvement: all were enrolled and evaluated by SIMP multidisciplinary group. Females accounted for 57% (12/21) of patients, the median age was 52 years (range 24-82). In the 67% (n=14/21) of cases, the major clinical symptom of spinal TB was back pain reported for a median of 4.5 months (range 1-12 months) before hospital admission. The interferon gamma release assay was positive in 75% (n=16/21) of patients. All patients performed MRI with gadolinium, which indicated spondylodiscitis in 90%. 18F-FDG-PET/CT revealed average maximum standardized uptake value (SUV max) of 12.54 (range 5.3-22) in 17/19 (89.5%). Bacteriological confirmation of TB was obtained in 86% of cases (n=18/21). One-third of patients (7/21) underwent surgery and 95% successfully completed the anti-TB treatment. CONCLUSIONS: Our data reveal that a multidisciplinary approach to spine tuberculosis facilitates early and accurate diagnosis and can improve medical and surgical management of this disease.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

Biomaterials as bone graft substitutes for spine surgery: from preclinical results to clinical study.

Vertebral fusion is performed in order to stabilize the spine in the presence of degenerative, traumatic or oncological pathologies that alter its stability. The autologous bone, harvested from the patient's iliac crest or from the lamina during surgery, is still considered the "gold standard" for spine fusion due to its osteogenic, osteoinductive and osteoconductive properties. However, several biological and synthetic bone substitutes have been introduced as alternatives for regenerating bone tissue. We have studied in particular the use of ceramic biomaterials prepared from hydroxypatite (HA), starting from in vitro analysis, through an in vivo study on ovine animal model and a post-market surveillance analysis, to finally design and perform a clinical study, which is ongoing in our Department. In the first step, HA-derived biomaterials were tested in vitro in the presence of bone marrow-derived human mesenchymal stem cells (hMSCs) and evaluated for their ability to activate precursor cells. In the second step, the biomimetic bone graft substitute SintLife® putty (MgHA) was evaluated in vivo. A posterolateral fusion procedure was applied on 18 sheep, where a fusion level was treated with MgHA, while the other level was treated with autologous bone. Microtomography and histological/histomorphometric analysis were performed six months of after surgery. In the third step, we reported the results of a post-market surveillance study conducted on 4 independent cohorts of patients (total 115 patients), in which HA-derived biomaterials were used as bone graft substitutes or extenders. Finally, a clinical study has been designed and approved by the Ethics Committee of our Institute and is currently ongoing. This study aims to evaluate the efficacy of the ceramic biomaterial SintLife® putty for bone replacement in patients treated by posterolateral fusion for degenerative spine disorders. HA biomaterials were effective in promoting the in vitro growth of hMSCs and their osteogenic differentiation. In the animal model, SintLife® putty has been effective in generating neo-formed bone tissue with morphological and structural features similar to those of the pre-existing bone. The post-market surveillance analysis has not reported any intra-operative nor early or late post-operative adverse events. Seven patients are currently recruited for the clinical trial designed to evaluate Sintlife efficacy for spine fusion (FU range: 1-7 months). No adverse events have been recorded. The first CT analysis performed at 6 months FU showed a good spine fusion. The study is ongoing. Our results, obtained from in vitro, preclinical and clinical studies, suggest that biomaterials derived from hydroxyapatite could be a valid alternative to autologous bone graft for vertebral fusion. This would potentially avoid or reduce the need of autologous bone harvesting and therefore, the risk of drawback-related side effects.

Denosumab: non-surgical treatment option for selective arterial embolization resistant aneurysmal bone cyst of the spine and sacrum. Case report.

OBJECTIVE: Aneurysmal Bone Cyst (ABC) is a cystic lesion of bone, occurring in 70% of cases as a primary lesion. Even if the metaphyseal region of long bones is more frequently involved, vertebral localization is not rare: ABC represents 15% of all primary spine and sacral tumours. Selective arterial embolization (SAE) represents the first treatment option for vertebral ABC. However, in few cases, multiple SAEs are not possible. The aim of this work is to report two cases of vertebral ABC unresponsive to SAE positively treated with Denosumab. PATIENTS AND METHODS: Two patients affected by ABC of the lumbar spine were treated by SAE without any response. Thus, the patients were submitted to an off-label treatment with Denosumab, following the same protocol already used in case of Giant Cell Tumour (GCT): 120 mg once a week for 4 weeks consecutively, then once every 40 days. RESULTS: In both cases, patients resulted to be pain-free after 11-13 Denosumab administrations and CT scan showed almost complete ossification of the lesions. CONCLUSIONS: The two cases reported here are not conclusive but they may support the project of a prospective study to confirm the effectiveness of Denosumab in ABC treatment as an alternative to SAE.

Medial olivocochlear reflex in ankylosing spondylitis patients.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease. Via autoimmune mediators, AS can damage the auditory system similar to other systems. Otoacoustic emission studies in AS patients showed that the damage that causes hearing loss was in the outer hair cells. The medial olivocochlear (MOC) reflex is used to evaluate the MOC efferent system (MOES), which includes the outer hair cells. The aim of this study was to evaluate the presence of subclinical damage in the inner ear with the aid of the MOC reflex test in AS patients with no hearing complaints. PATIENTS AND METHODS: Thirty-four patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. Otoacoustic emission responses, MOC reflex results, and frequency-specific and total suppression findings were compared between the groups. The relationship between clinical and laboratory findings for the AS patients, and the MOC reflex data were also investigated. RESULTS: Reduced MOC reflex response (p = 0.04) and suppression (p = 0.019) were detected in AS patients. When the clinical and laboratory findings for the AS patients and the MOC reflex test results were compared, a significant correlation was found only between the MOC reflex and the erythrocyte sedimentation rate. CONCLUSION: The results showed that AS can damage the inner ear, especially the MOES, and can reduce the MOC reflex response without clinical hearing loss.

Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers.

Diagnostic value of the wideband acoustic absorbance test in middle-ear effusion.

OBJECTIVES: This study aimed to investigate the diagnostic value of wideband acoustic absorbance testing in otitis media with effusion. METHODS: This prospective study compared middle-ear wideband acoustic absorbance rates in three paediatric patient groups: a healthy group of 34 volunteers; 48 patients diagnosed with otitis media with effusion; and 28 patients with chronic effusion but no sign of effusion during myringotomy. The diagnostic value of absorbance testing was analysed with the receiver operating characteristic test. RESULTS: The wideband acoustic absorbance rate was significantly lower in the otitis media with effusion group than in both the otitis media and healthy groups at the 0.375-2 kHz averaged mean absorbance (p < 0.017 and p < 0.001, respectively). Receiver operating characteristic analysis showed the highest diagnostic value for the 0.375-2 kHz averaged mean (area under the curve 0.984), followed by those at 1 and 1.5 kHz (area under the curve: 0.973 and 0.967, respectively). CONCLUSION: The wideband acoustic absorbance test is more accurate for detecting middle-ear effusion compared with conventional 226-Hz tympanometry. Its practicality and objectivity suggest that the wideband acoustic absorbance test may be a better alternative for diagnosing otitis media with effusion.

Endoscopic cartilage tympanoplasty in chronic otitis media.

OBJECTIVES: The use of endoscopic techniques is becoming more widespread in otological and neuro-otological surgery. One such procedure, endoscopic tympanoplasty, is used in chronic otitis media treatment. This study aimed to analyse the results of endoscopic transcanal cartilage tympanoplasty. METHODS: Data of tubotympanic chronic otitis media patients who underwent transcanal endoscopic type I cartilage tympanoplasty between June 2012 and May 2013 were analysed. The main outcome measures were graft success and hearing improvement. RESULTS: Graft success rates were 94.3 per cent and 92.5 per cent at post-operative months one and six, respectively. Post-operative air-bone gap values were significantly improved over pre-operative values (p < 0.01). CONCLUSION: Transcanal endoscopic type I cartilage tympanoplasty is a minimally invasive, effective and reliable surgical treatment option for chronic otitis media.

Carotid Doppler ultrasound evaluation in patients with pulsatile tinnitus.

A wide range of conditions, including atherosclerosis, may lead to pulsatile tinnitus. The objective of this study was to evaluate the patients with pulsatile tinnitus by means of carotid Doppler ultrasound parameters. Thirty-four patients with pulsatile tinnitus were enrolled in the study. Internal carotid artery intima-media thickness (IMT), blood flow velocities and arterial lumen diameters (LD) were measured and compared with the control group. Mean end diastolic velocity (EDV) (32.29 ± 17.22) and IMT (1.06 ± 0.36) values were significantly higher and mean LD (6.69 ± 1.20) was significantly lower compared to the control group. Peak systolic velocity and EDV values were significantly higher in patients whose IMT were greater than 1 mm. Pulsatile tinnitus may be the first symptom of a severe, life threatening disease. Doppler sonography is a noninvasive, safe and easily applicable diagnostic tool for the evaluation of the vascular structures, in patients with pulsatile tinnitus.

Spina bifida occulta in high grade spondylolisthesis.

A 14-year-old boy presented with symptomatic high-grade dysplastic type spondylolisthesis, with a presence of spina bifida occulta, not diagnosed by plain radiographs, but confirmed on preoperative CT and MR. Circumferential fusion with partial reduction of L5/S1 was performed. Awareness of the coexistence of spondylolisthesis and spina bifida by an accurate preoperative planning is paramount to avoid iatrogenic damage to neural elements during surgery.

Spondylodiscitis in familial dysautonomia: a case report.

Familial dysautomonia (FD, or Riley-Day syndrome) is a rare but fatal autosomal recessive peripheral neuropathy caused by a point mutation in I-κ-B kinase complex associated protein (IKBCAP) gene. The disease, that affects primarily people of Ashkenazi Jewish origin, prejudices the development of primary sensory neurons determining depletion of autonomic and sensory neurons. Musculoskeletal problems include: spinal deformities, foot deformities, fractures and arthopathies. In this article we review a case of a 34 years old male of non-Jewish origin affected by FD presenting L2-L3 kyphosis and inability to walk due to chronic L2-L3 spondylodiscitis not surgically treated 14 years before as acute disease. De novo spondylodiscitis affecting patients presenting FD and its subsequent management was not previously described in the literature.

Surgical treatment of thoraco-lumbar fractures in sickle cell disease: a case report.

Sickle cell disease (or drepanocytosis) is a hemoglobinopathy characterized by an increase in viscosity and adhesivity of the typically sickle-shaped erythrocytes. The pathological osteo-articular involvement in the course of drepanocytosis is secondary to the avascular necrosis of the bone marrow, caused by vaso-occlusive episodes in the microcirculation during acute painful crises. Osteoporosis and extramedullary hematopoiesis are also consequences of the disease. The involvement of the spine is common, with clinical features ranging from simple changes in spinal morphology ("fish-mouth" appearance) up to vertebral bodies fractures with kyphotic deformity. In the presence of vertebral fracture, treatment options listed in the literature are conservative (rest, symptomatic therapy, orthosis), because of the high incidence of intra- and perioperative complications (acute respiratory syndrome, vaso-occlusive crisis…), in addition to the increased rate of implant failure. We report here a case of a young man affected by multiple pathological symptomatic vertebral fractures at the thoraco-lumbar junction, secondary to a well controlled but severe form of sickle cell disease. We decided to treat the patient surgically because of a worsening and potentially invalidating kyphosis deformity. We describe the surgical procedure and the management of a later complication consisting in the collapse of the osteoporotic vertebra below the instrumentation that required a surgical revision. Although a conservative approach is most frequently indicated, we believe that the surgical option should be considered when a clinical worsening occurs in a young patient with otherwise well-controlled disease.

Is lumbar drainage of postoperative cerebrospinal fluid fistula after spine surgery effective?

AIM: This study is a retrospective consecutive case series analysis of 198 patients who underwent spine surgery between 2009 and 2010. The aim of this paper was to assess the efficacy and safeness of bed rest and lumbar drainage in treating postoperative CSF fistula. Postoperative cerebrospinal fluid (CSF) fistula is a well-known complication in spine surgery which lead to a significant change in length of hospitalization and possible postoperative complications. Management of CSF leaks has changed little over the past 20 years with no golden standard advocated from literature. METHODS: Postoperative CSF fistulas were described in 16 of 198 patients (8%) who underwent spine surgery between 2009 and 2010. The choice of the therapeutic strategy was based on the clinical condition of the patients, taking into account the possibility to maintain the prone position continuously and the risk of morbidity due to prolonged bed rest. Six patients were treated conservatively (position prone for three weeks), ten patients were treated by positioning an external CSF lumbar drainage for ten days. The mean follow-up period was ten months. RESULTS: All patients healed their wound properly and no adverse events were recorded. Patients treated conservatively were cured in a mean period of 30 days, while patients treated with CSF drainage were cured in a mean period of 10 days. CONCLUSION: Lumbar drainage seems to be effective and safe both in preventing CSF fistula in cases of large dural tears and debilitated/irradiated patients and in treating CSF leaks.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

Osteoporotic vertebral fractures: a disabling and expensive disease of our century. A minimally invasive surgical technique to reduce the pain, the hospitalization, and restore the function.

BACKGROUND AND OBJECTIVES: Minimally invasive spine surgery has gained a great consent in the treatment of vertebral osteoporotic fractures. We perform a retrospective clinical and radiographic review on 32 consecutive patients (22 female and 10 male) surgically treated for a thoracolumbar osteoporotic fracture (type A) by a minimally invasive system. By this study, we propose to determine the safety and efficacy of an expandable, percutaneous, minimally invasive technique to reduce the disability caused by vertebral osteoporotic fractures. MATERIAL AND METHODS: We retrospectively reviewed 32 patients who were operated on between 2003 and 2004 by means of an innovative technique which employs an expandable system inserted by a minimally invasive approach into the vertebral body. Average age at surgery was 64.8 years (range, 27-82). All patients were mobilized in first post-operative day with no external immobilization and discharged from the Hospital in the second post-operative day. RESULTS AND CONCLUSIONS: This innovative technique which employs an expandable system inserted by a minimally-invasive approach into the vertebral body permits to obtain a double mechanical support for the vertebral plate, to partially reduce the fracture, to mobilize the patient immediately, reducing disability and costs related to the vertebral osteoporotic fractures.

Management of bone metastases.

Bone metastases are only apparently similar lesions, considering the large varieties of istotypes and the spread of the primary tumour. Although these metastases develop early and are not terminal events, they have to be considered as severe complications. When possible, surgical treatment can improve the history of the patient in terms of life expectancy and quality of life. The approach to these lesions should be multidisciplinary in collaboration with oncologists and radiotherapists. In fact the average of survival of these patients has increased in recent years. The evolution of anesthesiological techniques permits surgical treatments that once were considered prohibitive. The application of new adjuvant therapies increases the effectiveness for surgical treatment. Controversy exists over the most appropriate treatment for patients with bone metastatic disease. The purpose was to determine the best sequential process to arrive at the most appropriate treatment considering the individual general conditions and the parameters of the metastases. As the number of treatment options for metastatic bone disease has grown, it has become clear that effective implementation of these treatments can only be achieved by a multidisciplinary approach.

Major bone defect treatment with an osteoconductive bone substitute.

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided by musculoskeletal tissue bank, heterologous bone graft (xenograft), or prostheses, each one of them dealing with both specific advantages and complications and drawbacks. The main concerns related to these techniques respectively are: donor site morbidity and limited available amount; possible immune response and viral transmission; possible animal-derived pathogen transmission and risk of immunogenic rejection; high invasiveness and surgery-related systemic risks, long post-operative. physical recovery and prostheses revision need. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes. Many synthetic substitutes are available, used either alone or in combination with other bone graft. Synthetic bone graft materials available as alternatives to autogeneous bone include calcium sulphates, special glass ceramics (bioactive glasses) and calcium phosphates (calcium hydroxyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium phosphate, BCP). These materials differ in composition and physical properties fro each other and from bone (De Groot in Bioceramics of calcium phosphate, pp 100-114, 1983; Hench in J Am Ceram Soc 74:1487-1510, 1994; Jarcho in Clin Orthop 157:259-278, 1981; Daculsi et al. in Int Rev Cytol 172:129-191, 1996). Both stoichiometric and non-stoichiometric HA-based substitutes represent the current first choice in orthopedic surgery, in that they provide an osteoconductive scaffold to which chemotactic, circulating proteins and cells (e.g. mesenchymal stem cells, osteoinductive growth factors) can migrate and adhere, and within which progenitor cells can differentiate into functioning osteoblasts (Szpalski and Gunzburg in Orthopedics 25S:601-609, 2002). Indeed, HA may be extemporarily combined either with whole autologous bone marrow or PRP (platelet rich plasma) gel inside surgical theatre in order to favour and accelerate bone regeneration. A case of bifocal ulnar bone defect treated with stoichiometric HA-based bone substitute combined with PRP is reported in here, with a 12-month-radiographic follow-up.

Glial heterotopia of the middle ear.

A choristoma is the presence of histologically normal tissue in an area where it is not normally located. The most frequently reported choristoma of the middle ear is salivary choristoma. Heterotopic brain tissue is very uncommon in the middle ear and mastoid. We present a rare case of glial choristoma of the middle ear, together with a review of the literature.

Relationship between the frequency of autonomic dysfunction and the severity of chronic obstructive pulmonary disease.

OBJECTIVE: The relationship between the frequency of autonomic dysfunction (AD) and the severity of chronic obstructive pulmonary disease (COPD) has not been exactly known, despite its importance in the pathogenesis of COPD. Therefore, we aimed to evaluate the relationship between the clinical stage severity of the disease and the frequency of AD in COPD patients. METHODS: The frequency and type of AD were determined according to the clinical severity of 35 stable COPD patients. The results were compared between the mild and moderate-severe COPD groups. Sympathetic system (SS) was evaluated with sympathetic skin response (SSR), QT and QTc intervals (ms) analyses. Parasympathetic system was evaluated with the heart rate interval variations (RRIV). RESULTS: For the total group, an AD was detected in 20 patients (57%), a parasympathetic dysfunction (PD) in 14 (40%), a mixed-type dysfunction in five (14%) and a sympathetic dysfunction (SD) in only one patient (3%). For the 12 mildly affected patients, there were cases of isolated SD in only one patient (8.5%), isolated PD in five (42%) and AD in six patients (50%). For the 23 moderate-severe COPD patients, mixed AD was detected in five patients (22%), isolated PD in nine (39%) and AD in 14 patients (61%). There were no significant differences between the two patient groups, neither for isolated parasympathetic and sympathetic, mixed form nor for total AD (P>0.05). CONCLUSIONS: The results suggested that PD was dominant in patients with COPD. However, the frequencies of autonomic parasympathetic and sympathetic dysfunction did not increase significantly with the severity of COPD. The severity of hypoxemia and/or airflow limitation may not be the only unique or definite reason for AD in COPD, as there was not an exact correlation between the presence of AD and the severity of airflow limitation and hypoxemia.