Pain assessment in children with cognitive impairment andchronicillness such as cerebral palsy or syndromic diseases ischallenging,and a clinical diagnosis of urinary tract infection orlithiasis canbe difficult. Remarkably, these patients are prone tobe affected byurinary stones, due to several predisposing factorssuch ashypercalciuria, bone demineralization,dehydration5 andtopiramate treatment forconcomitant epilepsy6.Struvite stones are a subset ofkidney stones, composed of magnesiumammonium phosphate (struvite)and calcium carbonate-apatite, whichform as a result of urinarytract infections with urease-producingpathogens. It is known thatthis type of stone is formed quickly,within a few weeks, in thepresence of urease producingbacteria7, from generasuch as Proteus,Providencia, Klebsiella, Staphylococcus. When theproduction ofammonia increases and the urine pH is high, thesolubility ofphosphate decreases, and struvite stones candevelop.
Prevalence of struvite stones in children has decreased overthepast decades: in France, they accounted for 11% of allurinarystones in the 1980s, then reduced to 6% inthe2000s8. Inaretrospective analysis, Gnessin et al.9 showed how immobile patientswithmusculoskeletal anomalies were prone to form struvite stones(18.4%vs. 6.2% in the control group). This event is due to theseveralrisk factors of UTIs in this population, such as incompletebladderemptying, vesicoureteral reflux, catheterization,neurogenicbladder10.
Clinical presentation of struvite stones substantiallydiffersfrom other stone types: typical renal colic is not alwayspresent,while flank or abdominal pain accounts for nearly 70%,followed byfever (26%) and gross hematuria (18%)11.
Diagnostic workup should include urinalysis, renal andbladderculture, and ultrasonography, which can detect a denselycalcifiedmass, producing marked posterior acoustic shadowing;indeed, aplain radiograph can also be able to identify radiopaqueimages,appearing as branching calcific densities overlying therenaloutline. Stone culture is recommended to identifyurease-producingbacteria and direct antibiotic therapy, sincebacteria identifiedby urine culture do not always match thosecultured from thestone12.
Treatment includes an initial antibiotic regimen, suchasamoxicillin-clavulanate or cefixime, before an eventualremoval.Timing and duration of therapy have not beendefinitivelyestablished: 1–2 weeks of enteral antibiotics specificfor urineculture are recommended, if available, with the additionofbroad-spectrum parenteral preoperativeantibiotics13. Aftertreating the episode, imagingand urine cultures should be repeatedwithin 3 months to confirmstone-free status or identifyrecurrence11.
Since the response to pain and its expression in thispopulationis heterogeneous, recognition may be delayed; however,theexperience of pain is often persistent and frequent, sometimesevenon a daily basis14.
Specific pain assessment scales (r-FLACC15, INRS16, NCCPC-R17, PPP18) have been introduced based ontheobservation of pain behaviors, none of which are recommendedonanother, however all being more precise than genericpainassessment tools19.Themain advantage of these scales is that they include physiologicandbehavioral items aiming at complete pain recognition. Thesescales’main disadvantage is that they require minimal specifictrainingand are more time-consuming. The revised Face, Legs,Activity, Cry,Consolability (r-FLACC) scale(Table 1) is based on 5items, with a score rangingfrom 0 to 10; it has been rated bynurses and physicians as havinghigher clinical utility in terms ofcomplexity, compatibility, andrelative advantage when compared tothe Non-Communicating ChildrenPain Checklist-Postoperative Version(NCCPC-PV)20,21.The latter appears more suitable inthe absence of a pre-definedpain assessment with parents, asrequired by the revised FLACC.Overall these scales should be usedaiming at individualization ofeach child specific pain behaviors,such as the misleading“freezing,” laughter or self-injuriousbehaviours, establishing ashared knowledge, and common languagewith parents. Broader use ofthese tools can help go beyond falsebeliefs such as the allegedindifference to the pain of some ofthese children or the“neuro-irritability” sometimes used to explainincreased tone andmovement. Remarkably, pain assessment andmanagement in thesechildren should never disregard a positiveinteraction with theirparents, which remain the best proxy measureof their kids’pain22. Amilestonepaper23described howexperiential learning leads mothers to “develop asense ofknowledge”of their children, managing to be competentinterpretersand translators of their sons’pain and finding the bestbalancebetween pain treatment and adverse consequences ofpainmedications. Health professionals should support this processsothat recognition and action based on parent’s concerns willhelpreach the best pain-related decisions about their children.Thisprocedure requires a specific attitude of empathy and theabilityto listen. The role of parents is also crucial indistinguishingfear and anxiety from pain. In children with moderateto severecognitive impairment, anxiety, and fear have been shown toplay anessential role in procedural pain and worsen its perceptionandimpact.. Their relevance should not be underestimated and shouldbeapproached in a holistic perspective24. A recent study demonstratedasignificantly different cortical activation patternduringvenipuncture in children with CPI compared to healthypeers,suggesting that a possible lack of frontal to limbicareasconnection may cause an impaired controlofemotions25.
Pain assessment and diagnosis.
A proposal for a possible diagnostic workup for pain inpatientswith cognitive impairment is shown inFig. 2.
When trying to address the different causes fromanepidemiological perspective, based on the frequency ofevents,various aspects should be considered.
The issue of painful contractures and dystonia should bemanaged,with a child neurologist and physiotherapist in order tooptimizethe use of splints, tutors, as well as, the need forbaclofen orbotulinum toxin treatment. Intractable pain due to adislocated hipmay be approached with an intra-articular steroidand a topicalanesthetic injection, which may allow months ofwellbeing26.
The gastrointestinal tract is one of the most common sourcesofpain among these patients. Impaired gastrointestinalmotility,insufficient hydration, and immobility lead toconstipation in upto 75% of patients, and an adequate amount offiber should beprovided to them in a delicate balance through whichhigh fiberformulas can slow down gastrointestinalemptying27.
Gastric emptying in children with a PEG and Nissenfundoplicationmay be delayed causing pain and nausea. On the otherhand, anaccelerated gastric emptying can be facilitated by anextensivelyhydrolyzed formula, but can cause either a persistentunpleasantsense of gastric emptying or even a dumping syndromewith anirritable, sweaty and restless child with hypoglycemia twohoursafter the meal. In this perspective, a trial with adifferentfeeding should always be thought28.
GERD should be considered an unlikely cause of pain inpatientsalready treated with adequate dosage proton-pumpinhibitors, whosetherapy can be continuedindefinitely29. Ifpresent, the PEG tube should beexamined to rule out gastrostomyinfections, granuloma,dislocation, occlusion, or buried bumpersyndrome.
Even when no specific concerns are identified, adentalassessment should be deemed if not already performed in thepastyear30.
Osteopenia is found in up to 95% of non-ambulating childrenwithcognitive impairment, 20% will experience a femoral fractureduringtheir life31,with adefinite risk of recurrence. Radiography or bone scan shouldbeperformed to rule out fractures or hip dislocationswhenpositioning, bathing, or dressing are difficult because ofthepain. If osteopenia-related back pain is suspected, especiallyincase of pain that worsens at night or while the child is moved,anex juvantibus trial with bisphosphonates maybeconsidered32. Lastbutnot least, the urinalysis to detect an infection and renalandbladder US to rule out stones should besystematicallyperformed33.
A consult with a child neurologist with specific experienceinthe field should always be considered when a clear cause isnotidentified, to rule out and treat possible dystonic disorders,ormore rare epileptic equivalents that need a specifictherapeuticapproach such as tetrabenazine34.
Once ruled out the above causes, an empirical medicationtrialdirected to neuropathic pain should be evaluated whileconsideringfurther invasive diagnostic tests in children withlong-standingirritability and pain behaviors.
Remarkably some syndromes, as the Noonan syndrome,arespecifically associated with an higher risk ofneuropathicpain35.
Given its safety and its effect on peripheral andcentralneuropathic pain, visceral hyperalgesia, autonomicdysfunction andspasticity in adults, gabapentin is an off-label butreasonablefirst-line choice30.The benefit of this therapy wouldindirectly confirm theneuropathic source of pain and avoidrepeating testing andinterventions for months in search of a cause,which often delaysappropriate pain management.
Sleep quality should be addressed as this is a relevant issueinchildren with chronic or recurrent pain36. Remarkably, a sleep disorder canalsobe mistaken for chronic pain, due to the reciprocal influenceofthese domains37.Finally, in cases of extreme pain anddystonia that do not respondto conventional treatment, thesymptomatic intranasal use ofdexmedetomidine at home could beconsidered in the setting ofpalliative care38– 40.