The spectrum of neurological manifestations of Crohn’s disease (CD) and ulcerative colitis (UC) is diverse and not fully understood. In addition to peripheral neuropathy,1, 2 mild autonomic impairment has been reported.3, 4 These problems themselves could also result in secondary neurological consequences, such as the exacerbation of enhanced physiological tremor. Indeed, some patients in our cohort2 complained of tremor. Hence, we hypothesized that enhanced physiological tremor would be more severe in patients with inflammatory bowel disease (IBD) than controls.
We evaluated the presence of enhanced physiological tremor and other neurological disorders in a cohort of consecutive patients with either CD (n = 31) or UC (n = 63), comparing them with healthy controls (n = 35). All CD and UC patients were enrolled at the Inflammatory Bowel Disease Clinic (Hospital Universitário Walter Cantídio, Brazil) and healthy controls were randomly selected from friends/relatives of these patients. Diagnosis of CD and UC were made by clinical, upper and lower endoscopy, radiological, and pathological assessments, according to accepted diagnostic criteria.5, 6 This study was approved by the Institutional Review Board of the Universidade Federal do Ceará. All participants signed an informed consent form upon enrollment.
After neurological evaluation, participants drew Archimedes spirals with each hand on a blank, standard, 8.5×11 inch sheet of paper, as described.7 Both spirals were rated by a clinically blinded senior movement disorders neurologist (E.D.L.) using a reliable and valid ordinal clinical rating scale (0–3). Data on demographics, medications, use of caffeine, and smoking and ethanol consumption within 24 hours of evaluation were collected. The one-way analysis of variance (ANOVA) followed by the Student–Newman Keuls test and Kruskal–Wallis one-way ANOVA plus Dunn’s test were used to compare the groups. Differences were considered significant if p<0.05. Logistic regression models were also used (outcome variable = diagnosis [UC + CD vs. controls]).
UC patients were older than controls (p<0.05): 44.7±1.9 (UC), 41.1±2.4 (CD), and 34.9±2.4 years (controls) but there was a similar gender distribution: control group (63.4%) compared with CD (51.6%) and UC patients (58.7%). A larger proportion of controls used caffeine 27(77.1%) compared with CD (12 [38.7%], p = 0.003) and UC (19 [30.2%], p<0.001). Smoking also differed by group (12 [38.7%] in CD, p = 0.0001 compared with 0 controls) and 14 [22.2%] in UC, p = 0.002 compared with controls). No IBD patients evaluated in our cohort were diagnosed with Parkinson’s disease, Parkinsonism, or essential tremor. No control patients had a diagnosis of Parkinson’s disease, Parkinsonism, or essential tremor, but a thorough neurological evaluation was not performed on this group. Some of the IBD patients did experience tremor while taking medications such as thalidomide. However, their Archimedes spirals were not included in this study.
Tremor scores on the right hand were similar in controls (0.49±0.06) vs. CD and UC (0.39±0.08 and 0.41±0.05, respectively, p>0.05). Tremor scores on the left hand also did not differ: 0.7±0.07 (controls), 0.57±0.08 (CD), and 0.64±0.06 (UC), p>0.05. The sum of tremor scores (right+left) was also similar among the different groups: 1.13±0.12 (controls), 0.95±0.15 (CD), and 1.05±0.09 (UC), p>0.05. In a bivariate logistic regression model, the sum tremor score (independent variable) was not associated with diagnosis (UC + CD vs. controls, odds ratio 0.81, 95% confidence interval 0.50–1.32, p = 0.40). Adjusting for age, gender, caffeine use, and smoking in a multivariate logistic regression model did not change the results (odds ratio 1.02, p = 0.95).
This study showed that patients with either CD or UC had no significant difference in the amount of enhanced physiological tremor compared with healthy volunteers. It is also possible that visual assessment of the Archimedes spirals may not be sensitive enough to detect minor tremor differences among these populations. Additional studies may be warranted.
This paper was part of the requirements for a PhD thesis presented at the Universidade Federal do Ceará by Dr. Gisele Ramos de Oliveira.
1 Funding: This study was supported by research grants from Coordination for Enhancement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq), Foundation for Support in Scientific and Technological Development of Ceará (FUNCAP), and Universidade Federal do Ceará.
2 Financial Disclosures: None.
3 Conflict of Interest: The authors report no conflict of interest.
Gondim, FA, Brannagan, TH 3rd, Sander, HW, Chin, RL and Latov, N (2005). Peripheral neuropathy in patients with inflammatory bowel disease.. Brain 128: 867–879, DOI: https://doi.org/10.1093/brain/awh429 [PubMed]
Oliveira, GR Teles, BC Brasil, EF et al. (2008). Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients.. Inflamm Bowel Dis 14: 389–395, DOI: https://doi.org/10.1002/ibd.20304 [PubMed]
Lindgren, S, Lilja, B, Rosen, I and Sundkvist, G (1991). Disturbed autonomic nerve function in patients with Crohn’s disease.. Scand J Gastroenterol 26: 361–236. [PubMed]
Lindgren, S, Stewenius, J, Sjolund, K, Lilja, B and Sundkvist, G (1993). Autonomic vagal nerve dysfunction in patients with ulcerative colitis.. Scand J Gastroenterol 28: 638–642. [PubMed]
Jewel, DP (1998). Ulcerative colitis.. Feldman, M, Scharschimdt, B F and Sleisenger, M H eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. Pathophysiology, Diagnosis and Management. 6th ed..Philadelphia: WB Saunders, pp. 1735–1761.
Kronbluth, A, Sachar, DK and Salomon, P (1998). Crohn’s disease.. Feldman, M, Scharschimdt, B F and Sleisenger, M H eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. Pathophysiology, Diagnosis and Management. 6th ed..Philadelphia: WB Saunders, pp. 1708–1734.
Hafeman, D, Ahsan, H, Islam, T and Louis, E (2006). Betel quid: Its tremor-producing effects in residents of Araihazar, Bangladesh.. Mov Disord 21: 567–571, DOI: https://doi.org/10.1002/mds.20754 [PubMed]