Abstracts
Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown.
Method
We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years.
Results
Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015).
Conclusion
In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia.
Chron's disease; inflammatory bowel disease; peripheral neuropathy; small fiber neuropathy; ulcerative colitis
Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida.
Métodos
Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos.
Resultados
A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015).
Conclusão
Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia.
doença de Crohn; doença inflamatória intestinal; neuropatia periférica; neuropatia de fibras grossas; colite ulcerativa
A wide variety of neurological diseases has been reported in patients with inflammatory
bowel disease (IBD). They may be part of the spectrum of extraintestinal manifestations
of Chron's disease (CD) and ulcerative colitis (UC) or secondary to nutritional or
treatment/iatrogenic complications11 Gondim FAA, Brannagan TH 3rd, Sander HW, Chin RL, Latov N.
Peripheral neuropathy in patients with inflammatory bowel disease. Brain.
2005;128(4):867-79. http://dx.doi.org/10.1093/brain/awh429
https://doi.org/10.1093/brain/awh429...
.
The list of the most common neurological diseases in IBD patients include migraine,
peripheral neuropathy, restless leg syndrome, demyelinating central nervous system
disease and cerebrovascular disease22 Dimitrova AK, Ungaro RC, Lebwohl B, Lewis SK, Tennyson CA, Green MW
et al. Prevalence of migraine in patients with celiac disease and inflammatory
bowel disease. Headache. 2013;53(2):344-55.
http://dx.doi.org/10.1111/j.1526-4610.2012.02260.x
https://doi.org/10.1111/j.1526-4610.2012...
,33 Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA et
al. Crohn’s disease is associated with restless legs syndrome. Inflamm
Bowel Dis. 2010;16(2):275-9.
http://dx.doi.org/10.1002/ibd.20992
https://doi.org/10.1002/ibd.20992...
,44 Morís G. Inflammatory bowel disease: an increased risk factor
for neurologic complications. World J Gastroenterol. 2014;20(5):1228-37.
http://dx.doi.org/10.3748/wjg.v20.i5.1228
https://doi.org/10.3748/wjg.v20.i5.1228...
,55 Katsanos AH, Kosmidou M, Giannopoulos S, Katsanos KH, Tsivgoulis G,
Kyritsis AP et al. Cerebral arterial infarction in inflammatory bowel diseases.
Eur J Intern Med. 2014;25(1):37-44.
http://dx.doi.org/10.1016/j.ejim.2013.08.702
https://doi.org/10.1016/j.ejim.2013.08.7...
.
However, there are conflicting reports about the exact prevalence of those neurological
conditions due to variable inclusion and disease-definition criteria employed by
different retrospective series55 Katsanos AH, Kosmidou M, Giannopoulos S, Katsanos KH, Tsivgoulis G,
Kyritsis AP et al. Cerebral arterial infarction in inflammatory bowel diseases.
Eur J Intern Med. 2014;25(1):37-44.
http://dx.doi.org/10.1016/j.ejim.2013.08.702
https://doi.org/10.1016/j.ejim.2013.08.7...
,66 Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal
complications of Crohn's disease and ulcerative colitis: a study of 700
patients. Medicine (Baltimore). 1976;55(5):401-12.
http://dx.doi.org/10.1097/00005792-197609000-00004
https://doi.org/10.1097/00005792-1976090...
,77 Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating
diseases in patients with inflammatory bowel disease. Gastroenterology.
2005;129(3):819–26.
http://dx.doi.org/10.1053/j.gastro.2005.06.022
https://doi.org/10.1053/j.gastro.2005.06...
,88 Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of
inflammatory bowel disease. Neurology. 1995;45(3):416-21.
http://dx.doi.org/10.1212/WNL.45.3.416
https://doi.org/10.1212/WNL.45.3.416...
,99 Elsehety A, Bertorini TE. Neurologic and neuropsychiatric
complications of Crohn’s disease. South Med J. 1997;90(6):606-10.
http://dx.doi.org/10.1097/00007611-199706000-00005
https://doi.org/10.1097/00007611-1997060...
,1010 Gendelman S, Present D, Janowitz HD. Neurological complications of
inflammatory bowel disease. Gastroenterology. 1982;82:1065.,1111 Figueroa JJ, Loftus Jr EV, Harmsen WS, Dyck PJ, Klein CJ. Peripheral
neuropathy incidence in inflammatory bowel disease: a population-based study.
Neurology. 2013;80(18):1693-7.
http://dx.doi.org/10.1212/WNL.0b013e3182904d16
https://doi.org/10.1212/WNL.0b013e318290...
,1212 Crespi V, Boglium G, Marzorati L, Zincone A, D’Angelo L,
Liberani A et al. Inflammatory bowel disease and periphera neuropathy
[abstract]. In: Proceedings of 4th Meeting of the European
Neurological Society; 1994 June 25-29; Barcelona, Spain. (J Neurol.
1994;241(Suppl 1):63)..
On 2004, we started a prospective cohort study to evaluate the exact prevalence of the
neurological complications in IBD patients and subsequently published the initial
results about the peripheral nervous system involvement1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
. Here, we will report the results of the initial 3 years
following the establishment of the cohort (2004-2008), comparing the prevalence of
neurological diseases among patients with CD and UC to that of disease-controls
(gastritis and dyspepsia). Part of this work has been published in abstract form
elsewhere1414 Gondim FAA, Teles BCV, Oliveira GR, Brasil EF, Aquino OS, Costa AMC
et al. High prevalence of neurological disorders in patients with inflammatory
bowel disease. Neurology. 2007;68:A105..
METHODS
We prospectively studied the prevalence of common neurological disorders in
consecutive patients with CD and UC seen at the outpatient IBD Clinic from the
Universidade Federal do Ceará. For this paper, we employed the methodology of a
nested case-control study, a relatively new observational design whereby a
case-control approach is employed within an established cohort. The nested
case-control design has the advantage of allowing for statistically efficient
analysis of data from an existing ongoing cohort with substantial savings in cost
and time. The diagnosis of CD and UC was made by experienced gastroenterologists and
was based on widely accepted diagnostic criteria, combining clinical, endoscopic,
radiological and pathological criteria1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
.
Standard protocol approvals, registrations, and patient consents
After approval by the Institutional Review Board from the Universidade Federal do Ceará, all patients with IBD who attended this outpatient clinic from 12/2004 to 7/2008 were invited to participate. Four patients (1 with CD and 3 with UC) either refused to participate or discontinued subsequent follow-up. A total of 121 patients were enrolled and accepted to be part of the study after signing a written informed consent and subsequently completed the neurological evaluation and follow-up. We have also evaluated the presence of the same neurological conditions in a group of 50 patients with gastritis/dyspepsia (disease-control group) to quantify and compare the risk of developping neurological diseases in CD and UC patients (including autonomic complaints), although this group did not have systematic checking of several blood tests conducted since conditions such as vitamin B12 deficiency are not common in this group.
Our protocol of neurological evaluation has been previously published1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
. Briefly, it consisted in a
standard neurological interview conducted by 2 board certified neurologists
(both certified by the American Board of Psychiatry and Neurology as well as the
Brazilian Neurology Board) with the help from medical students trained to
conduct medical records review and simple tests such as drawing of Archimedes
spirals1515 Oliveira GR, Aquino PS, Costa AM, Louis ED, Braga LL, Souza MH et
al. Tremor in patients with inflammatory bowel disease. Tremor Other
Hyperkinetic Mov (NY). 2013;3:tre-03-149-3042-1.. This was
followed by neurological exam, that included vibration assessment by
Rydel-Seiffer tuning fork, manual testing of major muscle groups (including
intrinsic hand muscles) and functional assessment (e.g. ability to arise from a
seated position without using the arms).
Headache assessment was a separate part of the protocol and will not be discussed
in the present publication. Their medical charts were reviewed and a standard
electrodiagnostic testing was performed based on their clinical complaints1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
. Patients with normal
electrodiagnostic testing but with sensory complaints not consistent with
myelopathy or ganglionopathy were considered to be affected by small fiber
neuropathy1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
. Additional
neurological work-up, including neuroimaging, electroencephalogram, visual and
somatosensory evoked potentials was performed based on the findings of our
initial neurological evaluation1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
.
Statistical analysis
Descriptive statistics, Chi-square test, Mann-Whitney (if failed normality test), ANOVA followed by Student-Newman Keuls test (for comparison of multiple groups) and t-test were used to compare the differences among the different groups. To compare and quantify the risk of the presence of the different neurological manifestations among CD and UC patients, we calculated the odds ratio (OR) for developing the most common neurological manifestations, with their respective confidence intervals and levels of significance (p was considered to be significant if less than 0.05).
RESULTS
A total number of 121 IBD patients, 70 with UC and 51 with CD were enrolled and completed the neurological evaluation. In addition, 50 control patients (gastritis/dyspepsia) underwent complete neurological evaluation. Three patients died during the observational period (1 with CD and 2 with UC), one due to a car accident and 2 due to unknown reasons.
Table 1 depicts the main demographic parameters of the 3 groups. Patients with CD were younger than UC and control patients (p < 0.05). A nonsignificant trend for higher proportion of women was seen on both UC and control groups. As expected, CD patients had lower levels of vitamin B12 and were more likely to develop B12 deficiency or borderline B12 levels. A higher proportion of CD patients had thyroid disease, but rates of DM and glucose intolerance (considering even transient abnormalities due to prednisone administration) were similar in both groups.
Table 2 details the OR analysis of the different neurological conditions in CD versus control patients, based on the results of our standardized neurological evaluation. As can be seen on Table 2, patients with CD were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.05), about 7 times more likely than controls to develop any type of neuromuscular condition (p = 0.001) and about 5 times more likely to develop autonomic complaints (p = 0.03). Despite the clear trend for the presence of higher prevalence of other conditions, there was no significant difference, most likely due to small sample (type II error).
Table 3 details the OR analysis of the different neurological conditions in UC versus control patients, based on the results of our standardized neurological evaluation. As can be seen on Table 3, patients with UC were 5 times more likely to develop large-fiber neuropathy than controls (p = 0.03) and about 3 times more likely than controls to develop any type of neuromuscular condition (p = 0.02). Despite the clear trend for the presence of higher prevalence of other conditions, there was no significant difference (most likely due to small sample, type II error) for strokes, hypoacusis and facial paralysis, even when one plots CD and UC together against control patients.
DISCUSSION
A recent Editorial Review has shown that the extra-intestinal manifestations of IBD
extend to every corner of the body1616 Loftus EV. Inflammatory bowel disease extending its reach.
Gastroenterology. 2005;129(3):1117-20.
http://dx.doi.org/10.1053/j.gastro.2005.07.042
https://doi.org/10.1053/j.gastro.2005.07...
. However, the magnitude of neurological involvement (both
central and peripheral) is still a matter of controversy, due to major differences
in the inclusion criteria and methodologies employed by the different studies.
Here, we present the initial results of the prospective study started in 2004 (acronym NEURODII), that was designed to evaluate the neurological complications in IBD patients. Among the initial 121 IBD patients enrolled (51 with CD and 70 with UC), neuromuscular manifestations were 3-7 times more prevalent in IBD patients than controls, especially large-fiber peripheral neuropathies, that were 5-7 times more prevalent in IBD patients than controls. A trend for higher prevalence of several other neurological conditions can be clearly seen on Tables 2 and 3, but no statistical significance for the other conditions was reached (even when one combines CD and UC patients versus controls), most likely due to the small sample, and the rarity of the events, leading to low power to detect diferences (type II error). Longer follow-up periods and larger sample may address this limitation over the next decade. In addition, as can be seen in Table 1, patients with CD and UC also had high rates of abnormal metabolic changes, such as transient or isolated high TSH levels (of unclear significance), borderline or high glucose levels during prednisone treatment or B12 changes. This is consistent with the findings from several other studies but also highlights the fact that most of the time the impact of metabolic abnormalities is important for the development of neurological conditions. Unfortunately, control patients did not undergo intense metabolic screening since they did not have neuropathic symptoms and we also do not have accurate rates of the prevalence of metabolic disorders at the state of Ceará, Brazil. However, it seems very clear that the IBD had far more metabolic complications than controls.
Our present results prospectively confirm the fact that peripheral neuropathy is the
most consistently reported neurological condition in IBD patients11 Gondim FAA, Brannagan TH 3rd, Sander HW, Chin RL, Latov N.
Peripheral neuropathy in patients with inflammatory bowel disease. Brain.
2005;128(4):867-79. http://dx.doi.org/10.1093/brain/awh429
https://doi.org/10.1093/brain/awh429...
,44 Morís G. Inflammatory bowel disease: an increased risk factor
for neurologic complications. World J Gastroenterol. 2014;20(5):1228-37.
http://dx.doi.org/10.3748/wjg.v20.i5.1228
https://doi.org/10.3748/wjg.v20.i5.1228...
,88 Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of
inflammatory bowel disease. Neurology. 1995;45(3):416-21.
http://dx.doi.org/10.1212/WNL.45.3.416
https://doi.org/10.1212/WNL.45.3.416...
,99 Elsehety A, Bertorini TE. Neurologic and neuropsychiatric
complications of Crohn’s disease. South Med J. 1997;90(6):606-10.
http://dx.doi.org/10.1097/00007611-199706000-00005
https://doi.org/10.1097/00007611-1997060...
,1212 Crespi V, Boglium G, Marzorati L, Zincone A, D’Angelo L,
Liberani A et al. Inflammatory bowel disease and periphera neuropathy
[abstract]. In: Proceedings of 4th Meeting of the European
Neurological Society; 1994 June 25-29; Barcelona, Spain. (J Neurol.
1994;241(Suppl 1):63).,1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
,1414 Gondim FAA, Teles BCV, Oliveira GR, Brasil EF, Aquino OS, Costa AMC
et al. High prevalence of neurological disorders in patients with inflammatory
bowel disease. Neurology. 2007;68:A105.. However, even the subject of peripheral neuropathy in IBD
patients has been challenged by a recent retrospective study with important
methodological limitations1111 Figueroa JJ, Loftus Jr EV, Harmsen WS, Dyck PJ, Klein CJ. Peripheral
neuropathy incidence in inflammatory bowel disease: a population-based study.
Neurology. 2013;80(18):1693-7.
http://dx.doi.org/10.1212/WNL.0b013e3182904d16
https://doi.org/10.1212/WNL.0b013e318290...
. They
have evaluated the medical charts from local residents of the Olmsted county (seen
at Mayo Clinic) from 1940 to 2004 to establish the prevalence of peripheral
neuropathy. The authors have concluded that neuropathy was uncommon in IBD
patients1111 Figueroa JJ, Loftus Jr EV, Harmsen WS, Dyck PJ, Klein CJ. Peripheral
neuropathy incidence in inflammatory bowel disease: a population-based study.
Neurology. 2013;80(18):1693-7.
http://dx.doi.org/10.1212/WNL.0b013e3182904d16
https://doi.org/10.1212/WNL.0b013e318290...
. There are multiple
explanations for this discrepancy. Our first conclusion is that the ascertainment of
the diagnosis of peripheral neuropathy from charts managed mostly by nonneurologists
(gastroenterologists) is not valid, since it is very unlikely that this specific
diagnosis will be registered in the chart (except for more obvious and dramatic
cases). This is true for several other conditions, e.g. if one conducts chart
reviews in patients admitted for the treatment of cirrhosis due to alcoholism, it is
very likely that they would find low percentages of the written chart diagnosis of
“neuropathy”, especially prior to 1990. In fact, in the seventies,
despite the widespread use of prolonged doses of metronidazole (known classic cause
of neuropathy), gastroenterologists considered that “Neuropathy is not common
in IBD and I have only seen a dubious case”1717 Coxon A, Pallis CA. Metronidazole neuropathy. J Neurol Neurosurg
Psychiatry. 1976;39(4):403-5.
http://dx.doi.org/10.1136/jnnp.39.4.403
https://doi.org/10.1136/jnnp.39.4.403...
. In this paper, the authors also do not report the
disease severity or the prevalence of other important conditions such as diabetes
mellitus (associated with rates of peripheral neuropathy up to 50%) or nutritional
deficiencies. It is still possible that an unrecognized bias, such as outstanding
management of nutritional deficiencies and immune status (referral bias) or genetic
background could explain those discrepancies. The latter is unlikely since in a
prospective study to evaluate neuropathic symptoms in IBD patients, very high
percentages of neuropathic symptoms were found even inside the United States1818 Shen TC, Lebwohl B, Verma H, Kumta N, Tennyson C, Lewis S et al.
Peripheral neuropathic symptoms in celiac disease and inflammatory bowel
disease. J Clin Neuromuscul Dis. 2012;13(3):137-45.
http://dx.doi.org/10.1097/CND.0b013e31821c55a1
https://doi.org/10.1097/CND.0b013e31821c...
.
Regarding the central nervous system manifestations, despite a trend for higher
prevalence of ischemic strokes, we have not found a higher percentage of strokes or
central demyelinating diseases in our CD or UC patients (even when both were plotted
against controls). This may be due to our small sample, since previous studies from
larger databases have found significantly higher rates of strokes and central
demyelinating diseases44 Morís G. Inflammatory bowel disease: an increased risk factor
for neurologic complications. World J Gastroenterol. 2014;20(5):1228-37.
http://dx.doi.org/10.3748/wjg.v20.i5.1228
https://doi.org/10.3748/wjg.v20.i5.1228...
,55 Katsanos AH, Kosmidou M, Giannopoulos S, Katsanos KH, Tsivgoulis G,
Kyritsis AP et al. Cerebral arterial infarction in inflammatory bowel diseases.
Eur J Intern Med. 2014;25(1):37-44.
http://dx.doi.org/10.1016/j.ejim.2013.08.702
https://doi.org/10.1016/j.ejim.2013.08.7...
,77 Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating
diseases in patients with inflammatory bowel disease. Gastroenterology.
2005;129(3):819–26.
http://dx.doi.org/10.1053/j.gastro.2005.06.022
https://doi.org/10.1053/j.gastro.2005.06...
,1616 Loftus EV. Inflammatory bowel disease extending its reach.
Gastroenterology. 2005;129(3):1117-20.
http://dx.doi.org/10.1053/j.gastro.2005.07.042
https://doi.org/10.1053/j.gastro.2005.07...
. However, when we grouped together CD and UC patients,
there are 5/121 IBD patients with strokes (0/51 in the control group) and 7/121 with
hypoacusis (versus 2/51 in the control group). Also, we have not found cases of
multiple sclerosis, although at least 1 of the patients labeled as “ischemic
strokes” could have been affected by demyelinating disease, since her disease
course was not consistent with abrupt onset of stroke symptoms and MRI findings were
equivocal. Unfortunately she did not complete a full work-up for demyelinating
diseases. These findings may reflect the lower percentage of demyelinating disease
in our region and contrast with other studies that have suggested that neurological
screening for central demyelinating disease may be warranted in IBD patients77 Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating
diseases in patients with inflammatory bowel disease. Gastroenterology.
2005;129(3):819–26.
http://dx.doi.org/10.1053/j.gastro.2005.06.022
https://doi.org/10.1053/j.gastro.2005.06...
,1919 Stovicek J, Liskova P, Lisy J, Hlava S, Keil R.Crohn’s
disease: is there a place for neurological screening? Scand J Gastroenterol.
2014;49(2):173-6.
http://dx.doi.org/10.3109/00365521.2013.867358
https://doi.org/10.3109/00365521.2013.86...
. Other authors have found high percentages of
abnormal neurological examination and MRI abnormalities on 37% of the IBD
patients2020 Babali A, Terzoudi A, Vadikolias K, Souftas V, Kleitsas K,
Pitiakoudis M et al. Peripheral neuropathy electrophysiological screening in
inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2013;25(5):539-42.
http://dx.doi.org/10.1097/MEG.0b013e32835ceca6
https://doi.org/10.1097/MEG.0b013e32835c...
. On the other hand,
peripheral nervous system involvement (either small and large-fiber neuropathy) was
very common in our patients, suggesting that early evaluation of subclinical or mild
symptoms may be important, especially in populations more prone to nutritional
deficiencies due to lower socio-economic status (like ours). Although, some authors
have not recommended screening for peripheral neuropathy in IBD patients1919 Stovicek J, Liskova P, Lisy J, Hlava S, Keil R.Crohn’s
disease: is there a place for neurological screening? Scand J Gastroenterol.
2014;49(2):173-6.
http://dx.doi.org/10.3109/00365521.2013.867358
https://doi.org/10.3109/00365521.2013.86...
, they have found significant
changes on neurophysiological parameters even in patients with subclinical disease,
similar to the findings from our present series and other older studies1313 Oliveira GR, Teles BC, Brasil EF, Souza MH, Furtado LE, Castro-Costa
CM et al. Peripheral neuropathy and neurological disorders in an unselected
Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis.
2008;14(3):389-95. http://dx.doi.org/10.1002/ibd.20304
https://doi.org/10.1002/ibd.20304...
,2121 Ståhlberg D, Bárány F, Einarsson K, Ursing B,
Elmqvist D, Persson A. Neurophysiologic studies of patients with Crohn's
disease on long-term treatment with metronidazole. Scand J Gastroenterol.
1991;26(2):219–24.
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Neurológicas em duas populações de pacientes com doença
inflamatória intestinal de diferentes nacionalidades [thesis].
São Paulo: Faculdade de Medicina de Ribeirão Preto;
2008.,2323 Coelho LSM, Oliveira GR, Costa AMC, Aquino PS, Braga LLBC, Souza
MHLP et al. Prevalence of somatic and autonomic small fiber neuropathy in a
cohort of patients with inflammatory bowel disease. Neurology.
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Peripheral neuropathy in inflammatory bowel disease patients: a prospective
cohort study. Scand J Gastroenterol. 2009;44(10):1268-9.
http://dx.doi.org/10.1080/00365520903199871
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,2525 Cetinkaya ZA, Cetinkaya Y, Gencer M, Sezikli M, Tireli H, Kurdas
OÖ et al. The relationship between quiescent inflammatory bowel disease and
peripheral polyneuropathy. Gut Liver. 2011;5(1):57-60.
http://dx.doi.org/10.5009/gnl.2011.5.1.57
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. Knowledge about the extent of neurological
involvement in IBD patients may become even more important with the advent of new
different therapeutic strategies to control the IBD course and its different
extraintestinal manifestations2626 Singh S, Kumar N, Loftus Jr EV, Kane SV. Neurologic complications in
patients with inflammatory bowel disease: Increasing relevance in the era of
biologics. Inflamm Bowel Dis. 2013;19(4):864-72.
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https://doi.org/10.1002/ibd.23011...
.
There were important therapeutic changes during this cohort study. In this study,
few patients were managed with inflixamab or alemtuzumab, and most were treated with
azathioprine and prednisone (especially for disease relapses). However, over the
last 5 years, those 2 medications were used far more frequently. The final report
from our cohort study will also attempt to establish whether the neuropathy course
was affected by those therapeutic changes. In a nested case-control within a
Brazilian cohort, we have found that patients with IBD are significantly more
affected by several neurological conditions (especially peripheral neuropathy and
other neuromuscular diseases) than controls. Those conditions are commonly mild, but
frequently misdiagnosed2727 Buskila D, Odes LR, Neumann L, Odes HS. Fibromyalgia in inflammatory
bowel disease. J Rheumatol. 1999;26(5):1167-71.. Further
studies are necessary to understand the exact nature of several sensory symptoms
experienced by IBD patients, that may include the involvement of complex changes on
central neuroplasticity and function of small fibers and sensory and autonomic
ganglia2323 Coelho LSM, Oliveira GR, Costa AMC, Aquino PS, Braga LLBC, Souza
MHLP et al. Prevalence of somatic and autonomic small fiber neuropathy in a
cohort of patients with inflammatory bowel disease. Neurology.
2010;74:A345.,2828 Lei Q, Malykhina AP. Colonic inflammation up-regulates voltage-gated
sodium channels in bladder sensory neurons via activation of peripheral
transient potential vanilloid 1 receptors. Neurogastroenterol Motil.
2012;24(6):575-85.
http://dx.doi.org/10.1111/j.1365-2982.2012.01910.x
https://doi.org/10.1111/j.1365-2982.2012...
. Long-term follow-up at the end
of the cohort study will also establish whether other conditions (especially
central) are also more prevalent in IBD patients.
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28Lei Q, Malykhina AP. Colonic inflammation up-regulates voltage-gated sodium channels in bladder sensory neurons via activation of peripheral transient potential vanilloid 1 receptors. Neurogastroenterol Motil. 2012;24(6):575-85. http://dx.doi.org/10.1111/j.1365-2982.2012.01910.x
» https://doi.org/10.1111/j.1365-2982.2012.01910.x
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Support: This study was sponsored by the Brazilian Research Council (CNPq), CAPES; FUNCAP (Fundação Cearense de Pesquisa) e Universidade Federal do Ceará.
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This manuscript was part of the requirements for a Habilitation thesis in Neurology presented by Dr. FAA Gondim at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo.
Publication Dates
-
Publication in this collection
Feb 2015
History
-
Received
19 July 2014 -
Received
18 Oct 2014 -
Accepted
06 Nov 2014