Pain in Children with Severe Neurologic Impairment

A recent commentary (JM Hauer JAMA Pediatrics; 2018. doi: 10.1001/jamapediatrics.2018.1531) addresses a common misconception regarding children with severe neurologic impairment (SNI):

“we don’t think she experiences pain”

She notes that literature since 2002 has challenged this assumption and that this is addressed in a new AAP clinical report as well (Hauer J, Houtrow AJ. Pediatrics 2017; 139: e20171002).

Key points:

  • Children with SNI may have moaning, grimacing, changes in tone/body position in reaction to pain and treatment can make them comfortable.
  • “We can never prove that such a child does not feel pain…When parents of children with hydranencephaly were asked whether their child felt pain, 96% indicated yes.”
  • Pain can trigger changes in catecholamines, cortisol and stress hormones.  “These considerations suggest that untreated chronic pain is more harmful to the well-being of children with SNI than is treatment used for pain.”
  • Sometimes no source for pain is identified.  This may be related to a CNS etiology (alteration of CNS) and may benefit from treatment.
  • “It is time to do away with the question of whether these children feel pain and focus on how we as individuals” identify/consider pain

My take: Reframing this issue is important; pain can occur in children with SNI.  At the same time, we have to be careful that some “palliative” measures could paradoxically prolong suffering in some children.

Related blog post: Suffering


Anti-TNF Therapy: Rapid Reduction in Pain in Crohn’s Disease

A pretty cool use of technology provides strong evidence that decreased pain perception in the brain of patient’s with Crohn’s disease (CD) occurs well before anti-inflammatory effects like mucosal healing (A Hess et al. Gastroenterol 2015; 149: 864-66). In this study, the authors prospectively identified 4 patients with CD and performed functional MRI on day -1, day 1, and day 27. Key findings:

  • In three patients, who responded with a decrease in Harvey-Bradshaw Index by ≥2 points 14 weeks after anti-TNF initiation, the pain signal induced by either finger tapping or compression (see cover below) was markedly improved 1 day after anti-TNF initiation.
  • In the CD non responder, there was only slight reduction in signals at 24 hours and no improvement from baseline at day 27.

My take: This study explains why so many patients with severe symptoms can be managed quickly as outpatients.  The effects of anti-TNF therapy on pain occur within 24 hrs!  Pretty cool. Screen Shot 2015-10-11 at 5.56.36 PM

IBD Update January 2015 (Part 2)

1. A retrospective study (Inflamm Bowel Dis 2014; 20: 2292-98) of 217 patients with inflammatory bowel disease(108 infliximab-treated, 109 adalimumab-treated) provides data which indicates that combination therapy (mainly with thiopurines) resulted in higher trough levels and lower antibodies to infliximab (ATI) than monotherapy in patients treated with infliximab (IFX).  This was not evident in the adalimumab (ADA)-treated patients. Overall, approximately 90% of study population had Crohn’s disease.

Key points from this study:

  • The majority of trough level/antidrug antibody levels were drawn due to loss of response.  This is a major limitation of this study.
  • Among IFX-treated patients, those with combination therapy had trough level of 7.5 mcg/mL compared with 4.6 mcg/mL.  In combination therapy patients, the incidence of ATIs was 5.7% compared with 29.8% in monotherapy patients.
  • According to this study, the dose of the immunomodulator (IM) did not significantly influence the infliximab trough level or antibody formation; that is, more than half of patients were receiving “suboptimal dosed IM” and their infliximab levels/ATIs were similar to those who were optimally-dosed.
  • Among those who were receiving combination therapy, the incidence of antibody formation was lower in IFX-treated patients who started IM concurrently with IFX compared with those in which IM was added subsequently.
  • There were many other limitations in this study, including the finding that 94% of monotherapy patients had received previous immunomodulator therapy.

Bottomline: This study suggests that combination therapy is beneficial for patients receiving infliximab (in agreement with the previous SONIC study) and may not be beneficial for patients receiving adalimumab; however, only a well-designed prospective study

2. Inflamm Bowel Dis 2014; 20: 2266-70.  This study with 749 patients from Sweden showed that a large number of inflammatory bowel disease patients did not receive with iron supplementation: “Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.”  This study showed frequent persistence of anemia one year after diagnosis, especially in children. At time of diagnosis, 55% of children and 27% of adults had anemia and 28% and 16% at one year followup, respectively.

My take: Treatment of the underlying IBD, often helps anemia.  However, in some patients treating the anemia with iron may help improve symptoms as much or more than other aspects of treatment.

3. Inflamm Bowel Dis 2014; 20: 2433-49.  Reviews pain management approaches for patients with IBD. The article emphasizes how pain can be multifactoral and that opiod-induced hyperalgesia may worsen pain.

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Bryce Canyon

Bryce Canyon