- Email: [email protected]
Impairment of short-term memory function and morphologic brain abnormalities in inflammatory bowel disease (IBD)
April 2000
age: 41.1 years) - were investigated using standard audiometry in addition to clinical examination of vestibular organs. An age and sex matched control group (n=50, 27 male, mean age: 38.2 years) with chronic diseases of the upper airways, mainly paranasal sinusitis, underwent the same investigations. Results: None of the patients in the control group exhibited any sign of hearing loss or otosclerosis. Sensorineural hearing loss (SNHL) exceeding that of the expected average hearing loss in the normal Western population was evident in five ulcerative colitis patients (10%) while 2 out of 50 patients (4%) with Crohn's disease exhibited typical audiological signs of otosclerosis. The difference between inflammatory bowel patients and controls was significant (p<0.05). Conclusions: SNHL should be considered among extraintestinal complications of ulcerative colitis. These symptoms might be masked by the severity of the underlying disease so that we suggest to consider hearing examinations in this group. This is clinically relevant since early recognition and prompt therapy can lead to restoration of hearing. In Crohn's disease otosclerosis appears more often than in the normal population which could be speculated to be due to an underlying measles virus infection which has also be inflicted in the pathogenesis of Crohn's disease.
1720 PROSPECTIVE ANALYSIS OF HEREDITARY AND ACQUIRED RISK FACTORS OF THROMBOEMBOLISM IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Michael Goeke, Christian Seifert. Viola Schulze, Andrea Schneider, Joerg S. Bleck, Siegfried Wagner, Arnold Ganser, Michael P. Manns, Mario von Depka, Medicine Hochschule Hannover, Hannover, Germany. Inflammatory bowel diseases (IBD) are associated with various extraintestinal complications. Conflicting data exist about the frequency of thromboembolic complications. The role of alterations of the coagulation system in IBD-associated venous thromboembolism (VTE) is a matter of debate. Aim of this study was to determine the frequency of VTE and prospectively evaluate the role of hereditary and acquired risk factors of VTE in ffiD patients. This included prothrombin G20210A mutation which has not yet been reported in IBD patients. Methods: In 70 consecutive IBD patients (CD:Crohn's disease, n=52; UC:ulcerative colitis, n=18), frequency of VTE since onset of IBD and patient characteristics including disease activity indices (CDAI and CAl) were determined. 255 healthy blood donors served as controls. In all patients and controls, fibrinogen, factor II, V, VIII, protein C (PC), free protein S (FPS), and antithrombin (AT) activity were assessed. In addition, gene analysis of FV Leiden (FVL), prothrombin G20210A (PT202IOA), and methylentetrahydrofolate reductase C677T (MTHFR) mutation was performed. Results: VTE was observed in 8.6% of ffiD patients (CD 6%,UC 10%). Fibrinogen (CD 47%; UC 56%), factor II (CD 49%; UC 56%), V (CD 59%; UC 61%), and VIII (CD 44%; UC 47%) activity was significantly elevated in ffiD patients compared to controls (5.1%, 29.1%, 28.3%, and 23.9%, resp.) with odds ratios (OR) of 17.9, 2.5, 3.7, and 2.6, resp. (I-test, p=O.OOI).Multivariate analysis including fibrinogen, factor II, V, and VIII activity revealed that fibrinogen, factors V and VIII but not factor II are independently increased in IBD patients (OR 21, 95% CI 4.3-100.2; OR 2.7, 95% CI 1.0-7.2; and OR 2.5, 95% CI 0.9-6.7). Frequency of FVL, PT2021OA, and MTHFR was not different between ffiD patients (CD 0%,0%, and 16,7%,resp.; UC 0%, 0%, 14,3%, resp.) and controls (0%, 0.4%, 11%, resp.). AT, PC, and FPS activity showed no differences between patients and controls. None of the patients with VTE showed FVL or PT20210A mutation. Conclusions: VTE is a frequent complication of ffiD. Fibrinogen, factor II, V, and VIII activities are elevated in IBD patients. In contrast, frequency of hereditary risk factors FVL, PT2021OA, and MTHFR mutations as well as AT, PC, and FPS deficiency is not different between patients and controls. These data suggest that instead of hereditary risk factors acquired alterations of the coagulation system probably account for the observed high frequency of thromboembolic events in IBD.
1721 GASTROINTESTINAL SYMPTOMS IN FIRST-DEGREE RELATIVES OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE. M. Scott Harris, Univ of Wisconsin Med Sch, Milwaukee, WI. Inflammatory bowel disease (IBD) is believed to have a genetic basis with a reported incidence of either ulcerative colitis (UC) or Crohn's disease (CD) in first-degree relatives of between 9 and 20%. Recognition of this association has brought symptomatic family members of afflicted individuals to medical attention for fear they too may develop IBD. The purpose of the present study was to assess the cause of gastrointestinal symptoms and the incidence of inflammatory bowel disease in symptomatic firstdegree relatives presenting newly for GI evaluation. METHODS: Between 1990 and 1999, 26 first-degree relatives of individuals afflicted with inflammatory bowel disease presented for evaluation of GI symptoms. 19 of their index family members had CD, and 7 had UC. Symptoms included abdominal pain or bloating in 21, diarrhea in 12, rectal bleeding in 6, and fatigue or other constitutional symptoms in 5. 16 underwent colonoscopy with visualization of the terminal ileum, 11 small bowel series, and 6 flexible sigmoidoscopy. Symptoms ranged in duration from 2 mos to 15 yrs (mean 2.1:!:2.2 yrs). Mean follow-up was 2.8:!:0.8 years. RESULTS: Of the 26 first-degree relatives who presented for evaluation, 2 were found to Crohns disase and I UC. In all 3 individuals, the disease was similar in location to that of the afflicted family member. 16 first-degree relatives met the Rome 1 Criteria for irritable bowel syndrome; 5 had lactose intoler-
AGAA313
ance; and 5 bleeding from an anal source. A single patient was found to have a dominant sigmoid polyp removed by later colonoscopy. In 7 patients, no cause for symptoms could be identified. In follow-up, 16 patients were symptom-free with reassurance or conservative medical management; 10 continued to have stable symptoms of irritable bowel syndrome or IBD. CONCLUSIONS: 1) Irritable bowel syndrome is the predominant GI disorder in first-degree relatives of individuals with IBD presenting newly for GI evaluation; 2) even when symptomatic, the incidence of IBD in these individuals is no more than their risk as a whole; 3) relatives of individuals with Crohn's disease appear more concerned about their risk and seek medical attention more frequently than relatives of individuals with ulcerative colitis; 4) when IBD does occur in a first-degree relative, it mimics the disease in their relatives.
1722 PULMONARY DYSFUNCTION IS FREQUENT IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Klaus R. Herrlinger, Mirja K. Noftz, Klaus Fellermann, Klaus Schmidt, Klaus Dalhoff, Eduard F. Stange, Med Univ, Luebeck, Germany. Background. Conflicting results exist about the occurrence of pulmonary involvement in patients with inflammatory bowel disease (IBD). In a previous study we showed tubular proteinuria in IBD patients to be a sensitive marker of disease activity. The aim of this study was to determine frequency and kind of pulmonary dysfunction and to look for a possible connection between pulmonary and renal extraintestinal involvement. Methods. 58 patients with IBD (36 CD-Crohn's disease and 22 UCulcerative colitis) and 22 control patients of similar age were investigated with respect to the following pulmonary function tests: blood gas analysis (BGA), FEV!, vital capacity (VT),lung CO transfer capacity (TLCO) and the Krogh factor (KCO). Disease activity was assessed by CDAI for CD and Truelove for UC and indirectly through renal proteinuria. Smoking habits and drug administration were documented. Results. 11136of CD and 9/22 of UC patients but none of the controls exhibited at least one pathological «80% predicted value) pulmonary test. In both CD and UC lung function tests were significantly impaired in comparison to the control group. This could be shown for FEVI (-10% in CD and -15% in UC,p:50.04), VT (-8% and -6% resp.,p:50.03) and TLCO (-24% and -19% resp.,p:50.004). There were no significant differences between both disease entities. The changes in pulmonary function were not dependent on disease activity in CD or UC. All UC but only 3/11 CD patients with pulmonary dysfunction showed tubular proteinuria. Summary. IBD patients show significantly decreased lung function tests in comparison to healthy control patients. This pulmonary dysfunction is subclinical and not dependent on disease activity. The link of this dysfunction to renal proteinuria was unexpected and needs further investigation.
1723 IMPAIRMENT OF SHORT-TERM MEMORY FUNCTION AND MORPHOLOGIC BRAIN ABNORMALITIES IN INFLAMMATORY BOWEL DISEASE (mD). Stephan H. Hollerbach, Frank Kullmann, Angela Geissler,Juergen Schoelmerich, Tilo Andus, Ruhr-Universitaet Bochum, Knappschaftskrankenhaus, Bochum, Germany; Dept of Medicine I, Univ of Regensburg, Regensburg, Germany; Dept of Radiology, Univ of Regensburg, Regensburg, Germany; Dept of Internal Medicine I, Univ of Regensburg, Regensburg, Germany. Background: In patients with inflammatory bowel disease (ffiD), little is known about extraintestinal involvement of the CNS and its putative contribution to the pathophysiology offfiD. The cognitive evoked cortical potentials (P3()o-EP) represent a sensitive electrophysiologic test to assess short-term memory processing by assessing cognitive function and neural pathways associated with vigilance, expectation and awareness of sensory stimuli. We studied P300-EP and brain morphology by using standard auditory evoked event-related cerebral potentials (P300) and MRI. MaterialslMethods: 26 patients with ffiD (39:!:12 years, 17 CD, 9 UC) were compared with 24 healthy controls. Patients with preexisting neurological disorders, smoking, or potentially interfering medication were excluded. Clinical evaluation of patients included disease duration, CDAl/CAI, duration and dose of steroid medication, and the minimal mental state test (MMT). Auditory evoked event-related cerebral potentials and cognitive evoked P300EP were recorded using a topographic approach with 22 scalp electrodes according to the 10120 International EEG system. Stimulation consisted of an acoustic oddball paradigm using a two-tone discrimination model (100012000 Hz). MRI was performed using a 0.5 Tesla-Magnetom SP63 (SIEMENS, Erlangen). Results: MMT was normal in all patients. MRI revealed focal white matter lesions in 75% of the patients studied. Mean peak latency of the P300wave was significantly increased in patients with ffiD (351::':msvs. 311::':rns in controls, p
age: 41.1 years) - were investigated using standard audiometry in addition to clinical examination of vestibular organs. An age and sex matched control group (n=50, 27 male, mean age: 38.2 years) with chronic diseases of the upper airways, mainly paranasal sinusitis, underwent the same investigations. Results: None of the patients in the control group exhibited any sign of hearing loss or otosclerosis. Sensorineural hearing loss (SNHL) exceeding that of the expected average hearing loss in the normal Western population was evident in five ulcerative colitis patients (10%) while 2 out of 50 patients (4%) with Crohn's disease exhibited typical audiological signs of otosclerosis. The difference between inflammatory bowel patients and controls was significant (p<0.05). Conclusions: SNHL should be considered among extraintestinal complications of ulcerative colitis. These symptoms might be masked by the severity of the underlying disease so that we suggest to consider hearing examinations in this group. This is clinically relevant since early recognition and prompt therapy can lead to restoration of hearing. In Crohn's disease otosclerosis appears more often than in the normal population which could be speculated to be due to an underlying measles virus infection which has also be inflicted in the pathogenesis of Crohn's disease.
1720 PROSPECTIVE ANALYSIS OF HEREDITARY AND ACQUIRED RISK FACTORS OF THROMBOEMBOLISM IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Michael Goeke, Christian Seifert. Viola Schulze, Andrea Schneider, Joerg S. Bleck, Siegfried Wagner, Arnold Ganser, Michael P. Manns, Mario von Depka, Medicine Hochschule Hannover, Hannover, Germany. Inflammatory bowel diseases (IBD) are associated with various extraintestinal complications. Conflicting data exist about the frequency of thromboembolic complications. The role of alterations of the coagulation system in IBD-associated venous thromboembolism (VTE) is a matter of debate. Aim of this study was to determine the frequency of VTE and prospectively evaluate the role of hereditary and acquired risk factors of VTE in ffiD patients. This included prothrombin G20210A mutation which has not yet been reported in IBD patients. Methods: In 70 consecutive IBD patients (CD:Crohn's disease, n=52; UC:ulcerative colitis, n=18), frequency of VTE since onset of IBD and patient characteristics including disease activity indices (CDAI and CAl) were determined. 255 healthy blood donors served as controls. In all patients and controls, fibrinogen, factor II, V, VIII, protein C (PC), free protein S (FPS), and antithrombin (AT) activity were assessed. In addition, gene analysis of FV Leiden (FVL), prothrombin G20210A (PT202IOA), and methylentetrahydrofolate reductase C677T (MTHFR) mutation was performed. Results: VTE was observed in 8.6% of ffiD patients (CD 6%,UC 10%). Fibrinogen (CD 47%; UC 56%), factor II (CD 49%; UC 56%), V (CD 59%; UC 61%), and VIII (CD 44%; UC 47%) activity was significantly elevated in ffiD patients compared to controls (5.1%, 29.1%, 28.3%, and 23.9%, resp.) with odds ratios (OR) of 17.9, 2.5, 3.7, and 2.6, resp. (I-test, p=O.OOI).Multivariate analysis including fibrinogen, factor II, V, and VIII activity revealed that fibrinogen, factors V and VIII but not factor II are independently increased in IBD patients (OR 21, 95% CI 4.3-100.2; OR 2.7, 95% CI 1.0-7.2; and OR 2.5, 95% CI 0.9-6.7). Frequency of FVL, PT2021OA, and MTHFR was not different between ffiD patients (CD 0%,0%, and 16,7%,resp.; UC 0%, 0%, 14,3%, resp.) and controls (0%, 0.4%, 11%, resp.). AT, PC, and FPS activity showed no differences between patients and controls. None of the patients with VTE showed FVL or PT20210A mutation. Conclusions: VTE is a frequent complication of ffiD. Fibrinogen, factor II, V, and VIII activities are elevated in IBD patients. In contrast, frequency of hereditary risk factors FVL, PT2021OA, and MTHFR mutations as well as AT, PC, and FPS deficiency is not different between patients and controls. These data suggest that instead of hereditary risk factors acquired alterations of the coagulation system probably account for the observed high frequency of thromboembolic events in IBD.
1721 GASTROINTESTINAL SYMPTOMS IN FIRST-DEGREE RELATIVES OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE. M. Scott Harris, Univ of Wisconsin Med Sch, Milwaukee, WI. Inflammatory bowel disease (IBD) is believed to have a genetic basis with a reported incidence of either ulcerative colitis (UC) or Crohn's disease (CD) in first-degree relatives of between 9 and 20%. Recognition of this association has brought symptomatic family members of afflicted individuals to medical attention for fear they too may develop IBD. The purpose of the present study was to assess the cause of gastrointestinal symptoms and the incidence of inflammatory bowel disease in symptomatic firstdegree relatives presenting newly for GI evaluation. METHODS: Between 1990 and 1999, 26 first-degree relatives of individuals afflicted with inflammatory bowel disease presented for evaluation of GI symptoms. 19 of their index family members had CD, and 7 had UC. Symptoms included abdominal pain or bloating in 21, diarrhea in 12, rectal bleeding in 6, and fatigue or other constitutional symptoms in 5. 16 underwent colonoscopy with visualization of the terminal ileum, 11 small bowel series, and 6 flexible sigmoidoscopy. Symptoms ranged in duration from 2 mos to 15 yrs (mean 2.1:!:2.2 yrs). Mean follow-up was 2.8:!:0.8 years. RESULTS: Of the 26 first-degree relatives who presented for evaluation, 2 were found to Crohns disase and I UC. In all 3 individuals, the disease was similar in location to that of the afflicted family member. 16 first-degree relatives met the Rome 1 Criteria for irritable bowel syndrome; 5 had lactose intoler-
AGAA313
ance; and 5 bleeding from an anal source. A single patient was found to have a dominant sigmoid polyp removed by later colonoscopy. In 7 patients, no cause for symptoms could be identified. In follow-up, 16 patients were symptom-free with reassurance or conservative medical management; 10 continued to have stable symptoms of irritable bowel syndrome or IBD. CONCLUSIONS: 1) Irritable bowel syndrome is the predominant GI disorder in first-degree relatives of individuals with IBD presenting newly for GI evaluation; 2) even when symptomatic, the incidence of IBD in these individuals is no more than their risk as a whole; 3) relatives of individuals with Crohn's disease appear more concerned about their risk and seek medical attention more frequently than relatives of individuals with ulcerative colitis; 4) when IBD does occur in a first-degree relative, it mimics the disease in their relatives.
1722 PULMONARY DYSFUNCTION IS FREQUENT IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Klaus R. Herrlinger, Mirja K. Noftz, Klaus Fellermann, Klaus Schmidt, Klaus Dalhoff, Eduard F. Stange, Med Univ, Luebeck, Germany. Background. Conflicting results exist about the occurrence of pulmonary involvement in patients with inflammatory bowel disease (IBD). In a previous study we showed tubular proteinuria in IBD patients to be a sensitive marker of disease activity. The aim of this study was to determine frequency and kind of pulmonary dysfunction and to look for a possible connection between pulmonary and renal extraintestinal involvement. Methods. 58 patients with IBD (36 CD-Crohn's disease and 22 UCulcerative colitis) and 22 control patients of similar age were investigated with respect to the following pulmonary function tests: blood gas analysis (BGA), FEV!, vital capacity (VT),lung CO transfer capacity (TLCO) and the Krogh factor (KCO). Disease activity was assessed by CDAI for CD and Truelove for UC and indirectly through renal proteinuria. Smoking habits and drug administration were documented. Results. 11136of CD and 9/22 of UC patients but none of the controls exhibited at least one pathological «80% predicted value) pulmonary test. In both CD and UC lung function tests were significantly impaired in comparison to the control group. This could be shown for FEVI (-10% in CD and -15% in UC,p:50.04), VT (-8% and -6% resp.,p:50.03) and TLCO (-24% and -19% resp.,p:50.004). There were no significant differences between both disease entities. The changes in pulmonary function were not dependent on disease activity in CD or UC. All UC but only 3/11 CD patients with pulmonary dysfunction showed tubular proteinuria. Summary. IBD patients show significantly decreased lung function tests in comparison to healthy control patients. This pulmonary dysfunction is subclinical and not dependent on disease activity. The link of this dysfunction to renal proteinuria was unexpected and needs further investigation.
1723 IMPAIRMENT OF SHORT-TERM MEMORY FUNCTION AND MORPHOLOGIC BRAIN ABNORMALITIES IN INFLAMMATORY BOWEL DISEASE (mD). Stephan H. Hollerbach, Frank Kullmann, Angela Geissler,Juergen Schoelmerich, Tilo Andus, Ruhr-Universitaet Bochum, Knappschaftskrankenhaus, Bochum, Germany; Dept of Medicine I, Univ of Regensburg, Regensburg, Germany; Dept of Radiology, Univ of Regensburg, Regensburg, Germany; Dept of Internal Medicine I, Univ of Regensburg, Regensburg, Germany. Background: In patients with inflammatory bowel disease (ffiD), little is known about extraintestinal involvement of the CNS and its putative contribution to the pathophysiology offfiD. The cognitive evoked cortical potentials (P3()o-EP) represent a sensitive electrophysiologic test to assess short-term memory processing by assessing cognitive function and neural pathways associated with vigilance, expectation and awareness of sensory stimuli. We studied P300-EP and brain morphology by using standard auditory evoked event-related cerebral potentials (P300) and MRI. MaterialslMethods: 26 patients with ffiD (39:!:12 years, 17 CD, 9 UC) were compared with 24 healthy controls. Patients with preexisting neurological disorders, smoking, or potentially interfering medication were excluded. Clinical evaluation of patients included disease duration, CDAl/CAI, duration and dose of steroid medication, and the minimal mental state test (MMT). Auditory evoked event-related cerebral potentials and cognitive evoked P300EP were recorded using a topographic approach with 22 scalp electrodes according to the 10120 International EEG system. Stimulation consisted of an acoustic oddball paradigm using a two-tone discrimination model (100012000 Hz). MRI was performed using a 0.5 Tesla-Magnetom SP63 (SIEMENS, Erlangen). Results: MMT was normal in all patients. MRI revealed focal white matter lesions in 75% of the patients studied. Mean peak latency of the P300wave was significantly increased in patients with ffiD (351::':msvs. 311::':rns in controls, p