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February 2002, Volume 26, Number 2, Pages 253-261
Table of contents    Previous  Article  Next   [PDF]
Paper
Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term longitudinal study
G Enzi, L Busetto, E Ceschin, A Coin, M Digito and S Pigozzo

Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

Correspondence to: L Busetto, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Padova, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy. E-mail: luca.busetto@unipd.it

Abstract

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterized by the growth of uncapsulated masses of adipose tissue. MSL is associated with high ethanol intake and complicated by somatic and autonomic neuropathy and by the infiltration of the adipose tissue at the mediastinal level. To date, the disease is considered as slowly progressive, but long-term longitudinal data are still lacking. In this study, a long-term follow-up of a large series of MSL patients is presented.

METHODS: We studied 31 patients with MSL (30 males and one female) first evaluated at our institution from 1973 to 1992. All patients were followed until 1998-1999 or until death, with a mean follow-up of 14.5±5.0 y (range 4-26 y). Both at baseline and during follow-up, the location and the size of the subcutaneous lipomatous fat depots, the presence and the extension of deeply localized lipomatous tissue, and the presence and the severity of both somatic and autonomic neuropathy were evaluated.

RESULTS: Eight MSL patients died during follow-up (25.8% of patients). A sudden death was proved to be the cause of death in three patients. All these three patients had severe autonomic neuropathy and none had coronary disease, acute myocardial infarction or other cardiac abnormalities. No signs or symptoms of coronary heart disease were present in the whole series. In addition to this high fatality rate, a substantial morbidity related to the occupation of the mediastinal space by the lipomatus tissue and to somatic neuropathy was also observed.

CONCLUSIONS: MSL is associated with a significant morbidity and mortality. Therefore, the definition of 'benign symmetric lipomatosis', still adopted by several authors, cannot be justified.

International Journal of Obesity (2002) 26, 253-261. DOI: 10.1038/sj/ijo/0801867

Keywords

adipose tissue; lipomatosis; Madelung's disease; Launois-Bensaude syndrome

Introduction

Multiple symmetric lipomatosis (MSL) was first described in the middle of the nineteenth century by Sir Benjamin Brodie, who in 1846 reported on two patients with symmetrical nucal lipomas 'as large as two oranges'.1 Forty years later, in 1888, Madelung described three patients with a typical symmetrical submental deposition of fat, subsequently named 'Madelung's collar'.2 In 1898, the condition was carefully characterised by Launois and Bensaude in a large series of patients as a well-defined clinical entity, named 'benign symmetrical lipomatosis'.3 The eponimous term of 'Launois-Bensaude disease' was subsequently frequently used in medical publications. The more descriptive designation of MSL has been proposed since 1977.4

MSL is characterised by the formation of multiple non-encapsulated lipomas with a symmetrical distribution and with sparing of distal arms and legs.5 The disease is more frequently diagnosed in middle-aged mediterranean subjects,6 but several cases have been also recently reported in north European7 as well as in non European patients.8,9 The disease is largely more prevalent in males.6 A history of high ethanol intake, chiefly in the form of red wine, is recorded in the large majority of MSL patients. In addition, upper airways compression and dislocation, dyslipidaemia, hyperuricaemia and impaired glucose tolerance have been frequently reported. The association with somatic and autonomic neuropathies was first documented in 1984.6

To date, the natural course of MSL is considered as slowly progressive, so that the disease is still defined as 'benign symmetrical lipomatosis'. In this study, a long-term follow-up of a large series of patients provides valuable information on morbidity and mortality in MSL, arguing against the definition of 'benign', still adopted by several authors.

Patients and methods

From 1973 we identified 68 patients (66 males and two females) with MSL. Diagnosis of MSL required the presence of multiple nonencapsulated lipomas and the recognition that these fat masses are symmetric and that the distal arms and legs are spared.5 The origin of the nonencapsulated masses from adipose tissue was always biopsy-confirmed. For the purposes of the present long-term longitudinal study, only patients with a possible follow-up of at least 6 y were considered. Therefore, only the 31 MSL patients (30 males and one female) first evaluated at our institution from 1973 to 1992 were included. All these patients underwent regular follow-up visits on a biennial basis until 1998-1999 or until death. The mean follow-up was 14.6±5.0 y (range 4-26 y). In case of death, the cause of death was determined from the autopsy report. If a postmortem examination was not performed or if the autopsy report cannot be traced, the cause of death was derived from an interview of the family physician.

At the first evaluation, the age at the onset of the disease, as evaluated from the patient's statement and interviews of relatives, was recorded and patients were classified, according to the distribution of lipomatous masses, as having type I or type II MSL. According to our previous definition,6 patients were defined as type I MSL if the fatty tumours maintained the aspect of distinct, well circumscribed, grossly round masses protruding from the body surface, and as type II MSL if the lipomatous tissue involved extensively and diffusely the subcutaneous fat layer, giving the patients the appearance of simple obesity (Figure 1). The daily alcohol intake, almost exclusively in the form of red wine, was also recorded from the patients and their relatives both at the first visit and during follow-up. Alcohol intake was categorised as low (less than 50 ml of ethanol per day), moderate (51-100 ml of ethanol per day) or elevated (more than 100 ml of ethanol per day).

At baseline and at the subsequent visits, height and body weight were measured. All anthropometric measurements were made with the subjects wearing only light clothes without shoes. Height was measured to the nearest 0.01 m using a wall-mounted stadiometer. Body weight was determined to the nearest 0.05 kg using a calibrated balance beam scale. BMI was calculated as weight (kg) divided by the height squared (m2).

Both at baseline and during follow-up, the location and the size of the subcutaneous lipomatous fat depots were evaluated on photographic images with standardised magnification. The presence and extension of deeply localised lipomatous tissue were evaluated by computerised tomography of the neck and the thoracic inlet. If clinically indicated, compression of the oropharyngeal tract and infiltration of oropharygeal mucosa were evaluated with video-laryngoscopy.

Somatic neuropathy was evaluated by neurological examination, including tests for pain, temperature and vibratory sensation, and deep reflexes elicitation. Electromyography (EMG) was also performed for the determination of the motor conduction velocity (MCV) at the ulnar and peroneal nerves and of the sensory conduction velocity (SCV) at the left sural nerve. An MCV of 44 m/s was assumed as the cut-off value for the diagnosis of motor neuropathy and an SCV of 43 m/s as the cut-off value for sensory neuropathy. These values represented the mean -2 s.d. of MCV and SCV of a group of age-matched control subjects previously studied at our institution.10 Autonomic neuropathy was evaluated by the Valsalva manoeuvre, heart rate variations on deep breathing, RR-interval variation in electrocardiographic record during lying to standing manoeuvre, diastolic blood pressure increments in sustained handgrip and postural hypotension. A detailed description of the tests we used for the diagnosis of an impairment of cardiovascular autonomic reflexes in MSL has been published previously.11

Finally, a selected set of laboratory examinations was performed including red blood cell count, liver function tests, blood glucose, total cholesterol and HDL-cholesterol fraction, triglycerides and plasma uric acid. Venous blood sampling was drawn early in the morning, after a 12 h overnight fast. Total cholesterol and triglycerides were measured by standard enzymatic-colorimetric methods.12,13 HDL-cholesterol was determined after selective lipoprotein precipitation with a magnetic antibody.14 LDL-cholesterol was calculated according to Friedewald.

Results

At baseline, the mean age of the 31 MSL patients included in this study was 50.1±10.2 y (range 33-76 y), and the approximate age at the onset of the disease was 41.8±11.4 y (range: 22-74 y). Two of the patients are natural brothers.

A large variability in body weight and body mass index (BMI) levels was observed (Table 1). The 22 patients (70.9%) categorised as type I MSL according to the distribution of lipomatous masses (see Methods) were thinner than the nine patients (29.1%) with type II MSL (Table 1; Figure 1). A small but significant increase in the BMI values, corresponding to a weight gain of 3.0±8.1 kg, was observed during follow-up (BMI at baseline vs BMI at the last evaluation: 24.2±3.3 vs 25.9±4.7 kg/m2; P<0.01). This small weight gain was observed in both type I and type II patients.

The mean daily ethanol intake at the first evaluation was 148.4±71.3 ml, ranging from 50 up to 400 ml/day. Only two patients (6.5%) showed a low alcohol intake, 14 patients (45.2%) had a moderate alcohol intake and 15 patients (48.3%) were heavy drinkers. None of the patients was a non-drinker at baseline. During the follow-up, the mean daily alcohol intake fell to 108.7±76.7 ml (P<0.05 from baseline). Alcohol consumption increased in four patients (12.9%), remained unchanged in nine (29.0%) and was reduced in 18 (58.1%). Four of these latter patients declared complete abstinence from drinking.

The most frequent location of the subcutaneous lipomatous masses at baseline was at the submental area (92.3%), followed by the nucal region (67.7%), dorsal and deltoid areas (54.8%), abdomen (45.2%), upper segment of arms (41.9%), mammary region (32.3%), and upper segment of legs (19.4%). During follow-up, the size of the lipomatous masses was unchanged in 16 patients (51.6%), enlarged in 13 (41.9%) and decreased in 2 (6.5%). Patients showing a reduction of the fat masses tended to have a lower alcohol intake at the last evaluation (50.0±70.7 ml of ethanol per day) than patients with stable disease (88.8±75.0 ml of ethanol per day), or patients with growing lipomatous masses (142.3±70.3 ml of ethanol per day; P for trend, 0.09 by ANOVA). The relationship between the changes of the size of the lipomatous masses and the variations of alcohol intake during follow-up is further analysed in Figure 2. The two patients showing a spontaneous reduction of the size of the lipomatous masses had a reduced ethanol intake at follow-up, with one of them being completely abstinent from drinking, whereas the four patients with an increased alcohol consumption suffered from a progressive increase of the subcutaneous fat depots.

An extension of the lipomatous tissue around the upper airways, associated with compression or dislocation of deeply located mediastinal structures, was observed by computerised tomography of the neck and the thoracic inlet in 10 patients at baseline and in a further two patients during follow-up, leading to a total of 12 cases (38.7%) of mediastinal involvement. In three of these patients, the lipomatous masses observed at the palatal, peri-pharyngeal, peri-laryngeal and peri-tracheal areas showed a rapidly progressive growth, causing dyspnoea, dysphagia and superior vena cava syndrome, and requiring a surgical toilette or tracheostomy (Figure 3). At baseline, about one-third of the MSL patients complained of symptoms related to the deep extension of lipomatous tissue at the level of the neck and of the thoracic inlet (excessive snoring in eight patients, dyspnoea in four, dysphagia in three). A severe obstructive sleep apnoea syndrome was present in one patient. The prevalence of these symptoms did not increase during follow-up (Figure 4). The reported frequency of dyspnoea and snoring was lower at the final control, due to the surgical removal of lipomatous tissue around the upper airways in the most severely affected patients.

At baseline, the most frequently reported symptoms were symptoms related to the presence of a somatic neuropathy. Paraesthesias at upper and lower limbs and muscular cramps were reported in 16 out of 31 patients (51.6%) and in 14 out of 31 cases (45.1%), respectively (Figure 4). The prevalence of such symptoms remained substantially stable (Figure 4). In one patient the signs of a severe peripheral neuropathy (bilateral plantar ulcers) manifested before the formation of fatty tumours at the neck. Although symptoms related to autonomic neuropathy (tachycardia, sudoresis, erectile dysfunction) were reported only by a minority of patients (Figure 4), objective signs of autonomic involvement (segmental hyperhydrosis, gustatory sweating, interosseal atrophy, tachycardia at rest, postural hypotension) were observed in 23 out of 31 patients (74.2%).

At baseline, electromyography demonstrated the presence of motor neuropathy in 26 patients (83.9%). The mean MCV was 40.4±3.9 m/s (range 35-51 m/s). Sensory neuropathy was detected in 23 patients (74.2%) and the mean SCV was 44.6±6.7 m/s (range 34-47 m/s). At the end of the follow-up period, MCV did not significantly differ from the initial values (42.2±4.4 m/s), while SCV showed a slight, but not statistically significant, decrement (40.1±7.1 m/s). At multiple regression analysis, no correlation emerged between motor and sensory conduction velocities and the duration of the disease or the daily alcohol intake, both at baseline and during follow-up.

The results of haematology and serum chemistry at baseline and at the final visit were reported in Table 2. At baseline, fasting blood glucose concentrations ranged between 72 and 148 mg/dl. Fasting glucose levels exceeding 110 mg/dl were observed in three patients (9.7%). Plasma uric acid concentrations ranged between 4.0 and 9.6 mg/dl. Uric acid levels exceeding the upper limit of the normal range (7.0 mg/dl) were found in 11 MSL patients (35.5%). Total cholesterol values ranged between 125 and 260 mg/dl. Plasma HDL-cholesterol levels ranged between 28 and 103 mg/dl, with a mean concentration significantly higher than the expected level of a normal adult male population. Triglycerides concentrations ranged between 60 and 820 mg/dl, exceeding the upper limit of normality (200 mg/dl) in six patients (19.3%). No inverse correlation was found between HDL-cholesterol and triglycerides values. LDL-cholesterol concentration was generally low, with no patients having LDL-concentrations higher than 160 mg/dl. No significant changes of these metabolic parameters were observed during follow-up.

Abnormalities of liver function tests (Table 2) were highly prevalent at baseline (12 out of 31 patients; 38.7%) and strictly related to the daily ethanol intake. Similarly, a red blood cells macrocytosis was recorded in 15 patients (48.4%) and an overt macrocytic anaemia in eight (25.8%; Table 2). Both liver function tests and haematology improved during follow-up in those patients who reduced ethanol intake.

During the follow-up period eight patients died (25.8% of patients; Table 3). The earliest death occurred 7 y after the onset of the disease in a 52-y-old man, and the latest 38 y after the onset of the disease in a 75-y-old man. No time trends in the rate of mortality were noted. The age at the onset of MSL and the duration of the disease did not differ between the patients who died and the whole series. A sudden death was proved to be the cause of death in three patients. All these three patients had severe autonomic neuropathy (Table 3). Autopsy records can be obtained in two of these three cases: coronary disease, acute myocardial infarction or other cardiac abnormalities were excluded in both patients. No signs or symptoms of coronary heart disease were present at admission and during follow-up in the whole of our series. Finally, in spite of the elevated alcohol intake, no patients in our series died from liver cirrhosis.

Discussion

The evaluation of both the clinical aspects and the outcome of a large series of patients with MSL presented in this study provides a complete description of the signs and the symptoms of this disease and gives some new insights into the natural evolution and the prognosis of MSL. This series represents the largest sample of MSL patients reported and the only published long-term study on this disease. Baseline clinical data confirm all the typical aspects of MSL and longitudinal data underline the presence of a substantial unsuspected disease-related mortality and morbidity.

The baseline characteristics of the 31 MSL patients evaluated in this study confirm the epidemiologic features of the disease that we previously described in a smaller number of cases.6 The onset of MSL is usually in the fourth or in the fifth decade of life, although the disease could occur also at very young ages (20 y). We also confirm that MSL is more prevalent in males.6 Moreover, our series includes two natural brothers, and we are aware of another familial case of MSL (a father and a son with a too short follow-up to be included in this study). Familial cases of MSL have also been reported by others,15,16 and an autosomic dominant inheritance of MSL has been proposed.17 Cutaneous and visceral lipomas have been frequently observed in Multiple Endocrine Neoplasia type 1 (MEN 1), and an allelic loss at the D11S146 locus was found to be associated with the formation of the lipomas in this syndrome. We previously analysed several samples of lipomatous tissue from MSL patients for a loss of heterozygosity on the chromosome 11 region, but all samples were found to be negative for allelic lesions.18 Thus, the genetic basis of inheritance in MSL remains to be elucidated.

The previously reported association between MSL and high ethanol intake6 is also confirmed in this study, with the large majority of MSL patients admitting a high alcohol intake at baseline. Moreover, our longitudinal follow-up firstly prove that alcohol discontinuation is associated with a slight regression of lipomatous depots and that an increase in ethanol consumption seems to accelerate the lipomatous growth. Therefore, ethanol seems to act as a trigger of the lipoma formation and growth. Abstinence from alcohol is to date the only non-surgical treatment found to be at least partially effective in MSL.

Finally, our series confirms the typical location of the lipomatous masses in MSL.6 Lipomatous masses are located at the nucal region, neck, dorsal, deltoid and mammary regions, abdomen and proximal segments of limbs. It is noteworthy that the sites of formation of the lipomatous tissue in MSL are almost the same of the brown adipose tissue (BAT) distribution in the human foetus.19 Moving from this observation, an origin of the lipomatous masses of MSL from BAT cells can be hypothesised.20 Indeed, it has been shown that cultured lipomatous MSL cells display a multivacuolar lipid deposition and a transient presence of large mitochondria with parallel cristae, both aspects recalling the morphological features of BAT preadipocytes in culture.21,22 Moreover, cultured MSL cells were characterised by a high basic fibroblast growth factor (b-FGF) stimulated proliferation rate,23 and b-FGF has been demonstrated to contribute to the enlargement of BAT during cold acclimation.24 Furthermore, fatty tumours in MSL grows mainly through a cell proliferation process,4 and the malignant degeneration of MSL lipomatous tissue has also been reported.9,25 Bundles of microfilaments and nuclear pockets, both suggesting a neoplastic-like proliferation process, have been observed in MSL cultured cell.22 In conclusion, all these findings seem to support the hypothesis of a tumoural-like growth of MSL cells from BAT precursors. On the other hand, the search in MSL tissue for the uncopling protein 1 (UCP1), usually considered a specific marker of BAT, gave both positive26 and negative8 results.

To date, MSL is considered a slowly progressive disease with a relatively benign natural course. This common belief is not supported, however, by scientific evidence and, to our knowledge, no long-term follow-up studies have been published so far. On the contrary, the major finding of our long-term study is the presence of a substantial unsuspected disease-related mortality in MSL patients. During a follow-up of 14.6±5.0 y (range 4-26 y), about a quarter of these patients died, corresponding to a mortality rate of 17.8 deaths/1000 patients/y. This fatality rate is three-fold higher than the mortality rate reported in 1994 in the male 50-54-y-old general population of the Veneto Region, Italy (6.1 deaths/1000 patients/y),27 and it is mainly inflated by the presence of three cases of premature mortality (age at death lower than 60 y; Table 3). The most frequently reported cause of death in our series was sudden death. Indeed, three patients with severe autonomic neuropathy and without other cardiac abnormalities suddenly died during the follow-up period. Two of these patients had an age at death lower than 60 y. Autonomic neuropathy has been reported to have a short-term high mortality rate in diabetic patients,28 and our longitudinal data suggest that an impairment of cardiovascular autonomic reflexes may well be a poor prognostic factor also in MSL patients. On the other hand, it should be noted that no signs or symptoms of coronary heart disease were present at admission and during follow-up in the whole of our series. This is an unexpected finding in a middle-aged male population and it could suggest a protective effect of MSL against coronary heart disease.

The absence of coronary heart disease in MSL patients could probably be explained by the characteristic metabolic profile of the disease. Lipid profile in MSL is characterised by a wide distribution of plasma cholesterol values, associated with an increase in HDL-cholesterol plasma levels and a decrease in LDL-cholesterol concentrations. Mean plasma triglycerides levels are slightly increased with a wide range of values, possibly related to the individual drinking habits, but their post-prandial removal rate was increased in MSL patients compared to normal subjects of the same sex and age.29 The classic inverse correlation between plasma triglycerides and HDL-cholesterol concentrations is not confirmed in MSL patients. A markedly increased adipose tissue lipoprotein lipase in vitro activity in MSL30 seems to be the more reliable explanation for both the increased HDL production and the more rapid clearance of the triglyceride-rich lipoproteins from the circulation. Such a lipid pattern could probably explain the very low incidence of coronary heart disease observed in our MSL patients. Other metabolic abnormalities previously reported in single cases or in small series of MSL patients include impaired glucose tolerance, hyperuricaemia and renal tubular acidosis.31,32,33 In our series, we did not find any case of tubular acidosis and impaired glucose tolerance or overt diabetes occur in about 10% of MSL patients, corresponding to the expected prevalence for a middle-aged male population. Finally, hyperuricaemia is prevalent in our series (35.5%), and it is probably one of the more specific metabolic alterations in this disease. The high ethanol intake frequently found in MSL patients could probably at least partly explain this association.

Besides a high mortality rate, the natural history of MSL in our long-term follow-up study is also characterised by a substantial disease-related morbidity. Compression, dislocation and infiltration of structures around upper airways and at the thoracic inlet, responsible for dyspnoea, dysphagia, snoring and obstructive sleep apnoea syndrome, occur in about 40% of MSL patients. Surgical removal of pharingeal and palatal fat accumulation was mandatory in two patients, and tracheotomy in one (Figure 3).

Finally, the most frequently reported and troublesome symptoms in MSL patients relate to the presence of sensory, motor and autonomic neuropathy. Paraesthesias, muscular cramps, tachycardia at rest, segmental hyperhydrosis, erectile dysfunction, achrocianosis, trophic ulcers and Dupuytren contracture affect some 90% of the patients. Both clinical and electrophysiologic signs of somatic neuropathy are still frequently present at baseline and no further relevant impairments of somatic neuropathy were observed during follow-up. Thus, MSL neuropathy seems to have an early onset, but a steady course. However, autonomic neuropathy showed a progressive impairment in most MSL patients. The severity and the evolution of somatic and autonomic neuropathy is not affected by the drinking habits of the MSL patients. This observation further proves that neuropathy in MSL is unrelated to elevated alcohol intake and has to be considered as a peculiar aspect of this disease.10,11,34 A decrease in mielinated nervous fibres in peroneal nerve biopsies was first described in 198610 and later confirmed.34 Several authors have reported on the association between MSL and mitochondrial dysfunction, mainly represented by a reduced cytochrome-C oxidase activity, ragged red fibres and multiple deletion in mitochondrial DNA.35,36,37,38 On the other hand, some patients with the myoclonic epilepsy ragged red fibres (MERRF) syndrome and the Aright arrowG transition at nucleotide 8344 presented with cervical lipomas resembling those of MSL.39,40 We recently reported that morphologic analysis of muscle biopsy samples from six patients with MSL suggested mitochondrial abnormalities and that the measurement of several mitochondrial enzyme activities in such samples demonstrated a significant decrease in the activity of several respiratory chain enzymes (cytochrome-C oxidase, succinic dehydrogenase and citrate synthetase).41 However, lymphocyte mitochondrial DNA analysis showed a MERRF point mutation in only one patient with MSL.41 Therefore, the significance of mitochondrial dysfunction in the pathogenesis of the lipoma formation and the other multisystemic clinical manifestations of MSL deserves further study.

In conclusion, our long-term study firstly demonstrated that MSL is associated with a significant morbidity and mortality. Both mortality and morbidity should be considered as disease-specific, the first being partially explained by sudden death related to autonomic neuropathy, the latter being sustained by the extension of lipomatous tissue at the mediastinal level and by somatic neuropathy. Therefore, we believe that the definition of 'benign symmetric lipomatosis' still adopted by several authors can no longer be justified.

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37 Klopstock T, Naumann M, Schalke B, Bischof F, Seibel P, Kottlors M, Eckert P, Reiners K, Toyka KV, Reichmann H. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology 1994; 44: 862-866. MEDLINE

38 Naumann M, Kiefer R, Toyka KV, Sommer C, Seibel P, Reichmann H. Mitochondrial disfunction with myoclonus epilepsy and ragged-red fibers point mutation in nerve, muscle and adipose tissue of a patient with multiple symmetric lipomatosis. Muscle Nerve 1997; 20: 833-839. Article MEDLINE

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Figures

Figure 1 Two patients with multiple symmetric lipomatosis (MSL). Left side: type I MSL, showing circumscribed fatty tumours protruding from the body surface. Right side: type II MSL, with a widespread deposition of lipomatous tissue mimicking the appearance of simple obesity.

Figure 2 Relationship between the changes of the size of the lipomatous masses and the variations of alcohol intake during follow-up in 31 MSL patients. Light grey bars represent patients showing a reduction of ethanol intake during follow-up, white bars represent patients with a stable ethanol intake, and dark grey bars represent patients with a further increase in alcohol consumption. All patients showing reduced lipomatous masses had a reduced ethanol intake, whereas all patients with a further increase in alcohol consumption showed an increase in the fat mass volume.

Figure 3 Evidence for a progressive occupation of the thoracic inlet in an MSL patient. Left: the patient at the first evaluation. Right: the same patient 8 y later with a superior vena cava syndrome and a tracheal stenosis requiring tracheostomy.

Figure 4 Variations in the prevalence of symptoms during follow-up in 31 MSL patients. Light grey bars represent the prevalence of symptoms at baseline and white bars represent the prevalence of symptoms at the final evaluation.

Tables

Table 1 Anthropometric data at the first evaluation in 31 patients with MSL

Table 2 Serum chemistry and haematology in 31 MSL patients at baseline and at the final evaluation

Table 3 Deaths in 31 MSL patients after a follow-up of 14.5±5.0 y (range 4-26 y)

Received 11 December 2000; revised 31 May 2001; accepted 6 July 2001
February 2002, Volume 26, Number 2, Pages 253-261
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