FormalPara Key Summary Points

Complex regional pain syndromes (CRPS) are best managed with a sympathetic block.

The patient described had a long-lasting case of CRPS, significantly limiting the ability to care for her well-being.

Considering her extremely young age (18 months), the decision to treat her pain with a sympathetic block was made after a long-lasting, non-successful, pharmacological therapy.

A sympathetic block was executed with every possible caution to prevent any potential unwanted effects.

Considering the brilliant results, and the exceptionality of the case, the authors have decided to publish this case report.

Introduction

Both adults and children may experience chronic pain sympathetically mediated, known as complex regional pain syndrome (CRPS). CRPS type I is more common in girls than in boys in the pediatric population [1]. The mean age at diagnosis is 12 years, and the lower extremities are more affected than the upper [1]. Based on case reports, children as young as 3 years old have been diagnosed with CRPS [2]. The youngest case of CRPS ever reported in the literature involved an upper limb ailment in a young girl aged two and half years [3].

The diagnosis of CRPS in such young ages is challenging since the specific causes of the syndrome are commonly unknown. Studies on the pediatric age group are generally lacking both for origin, pathophysiology, and the clinical aspects of CRPS. However, the pathogenesis of pediatric CRPS is not necessarily identical to that of adults [1]. CRPS is commonly attributed to a previous trauma that might be very minor like a sprain or twist and in some cases no obvious injury can be recalled. Unless trauma has been witnessed by the parents, diagnosis of such trauma in very young non communicating children cannot be confirmed, adding difficulties in the diagnosis [4]. Very young non-communicating children cannot give a full history of trauma (unless witnessed) and as well they cannot describe the characteristics of their pain [1].

Signs of CRPS can vary very much. They include hyperalgesia, allodynia, swelling with or without changes in skin color of the affected limb, dry skin, mottled skin, hyperhidrosis, and trophic changes of the nails and hair [4]. Children diagnosed with CRPS are functionally more impaired and psychologically distressed than children with other pain conditions [5]. Management of CRPS in children requires the utilization of interdisciplinary treatment programs, which incorporate cognitive behavioral therapy (CBT) with physical and occupational rehabilitation [6].

To date, there are no specific pharmacological management techniques recommended for pediatric CRPS, [1] and, to the best of our knowledge, there are no large-scale clinical trials in progress. Limited studies described the use of non-steroidal anti-inflammatory drugs (NSAIDs), amitriptyline, and a few case reports described the use of gabapentin for the treatment of pediatric CRPS patients.

Ketamine is an anesthetic with analgesic effect. It is a NMDA receptor antagonist. In addition, ketamine also acts on other non-NMDA pathways that affect pain and mood regulation [7]. It acts as an antagonist of nicotinic and muscarinic cholinergic receptors. There are several studies in the adult population on the efficacy of intravenous ketamine infusions for CRPS, including case reports of resistant cases [7, 8].

Invasive pain management intervention with single sympathetic blocks was the most used to treat CRPS in pediatrics, followed by epidural catheters and continuous sympathetic blocks [9]. Regarding the outcome of these interventions, reports showed improvement in pain intensity and functional disability scores in most patients. However, outcomes were seldom assessed with validated tools. Zernikow et al. [9] concluded that there is a weak level of evidence for the use of invasive interventions for the treatment of CRPS in children.

Long-term prognosis of pediatric CRPS is unknown and studies to date have yielded contradictory results [6]. CRPS-1 in childhood seems to be milder than in adults, with less atrophy and with a good short-term prognosis. The long-term prognosis needs further evaluation [9]. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Case Description

Method

Collection and publication of patient data were approved by the IRB of Dar Al Fouad Hospital, Giza, Egypt (DAF2023-19). Written informed consent was obtained from the father for both the intervention and the publication.

An 18-month-old baby girl was referred to the pain clinic with a history of severe lower limb pain that started 2 months earlier. Her parents were unable to recall any trauma before the onset of the pain syndrome. Before the incidental onset of pain, the girl had her normal growth in all aspects. She was able to take her first few steps while walking without assistance, with no known previous diseases or allergies.

The mother reported that the girl gradually started crying and pointing to her right knee. Over the next 2 weeks, the pain increased to cover the entire lower limb, and spread to the gluteus area by the third week. The mother informed us that the girl experienced continuous stinging pain for 24 hours, and diaper changes became problematic due to the severe pain. Due to a lack of sleep and poor appetite, the baby started losing weight. When she arrived at the pain clinic, her weight was 6700 g, significantly less than the mean normal weight at her age. The parents described the pain as excruciating and no one could touch her skin, especially around the right knee up to the gluteus area and down to the big toe.

During the first week they consulted the pediatrician who initially prescribed paracetamol 10 mg/kg oral syrup/6 hourly PRN. He then added ibuprofen syrup, 6 mg/kg every 8 h, and referred her to a pediatric orthopedic specialist. The specialist examined her with marked difficulty as severe allodynia and partial contraction of the right knee were present. He could not extend the patient’s leg. Hence, he ordered an X-ray image of the right lower limb and knee to exclude any bone lesions. All of the X-ray images were normal. She was suspected of having CRPS and was referred to the pediatric neurology department. Pediatric neurologists agreed on the suspect of CRPS, but as it is an exclusion syndrome, they did not have the possibility of an EMG that is usually performed in such a condition, to exclude nerve injuries. The exam would have been extremely difficult for the young patient without general anesthesia, which could have affected the results. Neurologists prescribed oral gabapentin 25 mg/day that was gradually escalated to 100 mg on three divided doses/day. They also added amitriptyline 5 mg that was increased to 10 mg at bedtime. The drugs' oral regimen represented the maximum possible dose for that age. The patient showed some improvement in sleep, and the pain appeared reduced and more localized around the knee. Still, she could not extend her knee, which was a little swollen and in a persistent condition of contraction at 45 degrees. The patient was referred for rehabilitation that could not be performed because of marked allodynia. The neurologist referred the patient to the pain clinic for a potential interventional treatment.

Therefore, the patient came to our attention after a journey of 2 months in the described conditions. She appeared emaciated and underweight (her body weight was 6700 g). She was also apprehensive, and showed an exaggerated fear of strangers, especially those in white coats. The pain score at rest was 8 out of 10 utilizing the FLACC scale [10]. Her right knee was semi-flexed at 45 degrees. She had marked allodynia in the right lower limb but mostly around the knee. There were not many dysautonomic signs (color and temperature changes) apart from mild edema around the knee. The parents could recall color changes in the form of redness, hotness, and edema, which accompanied the breakthrough bouts of pain. The right knee was permanently in a state of contracture at 45 degrees, without any possibility of passive extension. She could contract it more to some degree but could not extend it at all. She lost the ability to walk, as she could not perform any weight-bearing on her partially flexed right leg. There was no other abnormality. After discussing the risks and potential benefits of the planned intervention and the limitations in the literature regarding similar extremely young cases, the parents approved the trial procedure to save the limb of their baby girl and restore its function. Written informed parental consent was obtained for the intervention and the use of the patient’s anonymized data for the publication of this case report.

Case Management

The patient was introduced to the preparation room by her mother. An intravenous line was established after local anesthesia using EMLA cream. Sedation with intravenous midazolam (0.05 mg/kg) was initiated as per our hospital protocol. Standard monitors were used, including pulse oximetry, noninvasive blood pressure measurements, and ECG. The patient was transferred to the intervention room accompanied by her mother. Premedication with i.v. 0.02 mg/kg atropine was administered followed by intravenous ketamine at a dose of 2 mg/kg to initiate general anesthesia. A face mask was used with sevoflurane 1–2%, followed by laryngeal airway mask (LAM) application. At this point, the mother was requested to leave the room. Prone position with a soft roll under the pelvis was achieved and a skin temperature probe was applied to the right calf muscle area. Spontaneous breathing of 50% oxygen mixed with air and sevoflurane 1% was aided by manually assisted ventilation, if needed.

Intervention

Under strict aseptic conditions and fluoroscopy guidance, L3 vertebrae was visualized (Fig. 1). The C-arm was placed in the oblique plane until the end of the transverse process was aligned with the anterior aspect of the vertebral body (Fig. 2). For the intervention, we used a 4-cm-long trocar of a 22G cannula, which was shorter than any available spinal needle. A needle was introduced and tunneled vision was obtained (Fig. 3). Once the trajectory was confirmed, a lateral view was obtained to determine the depth of the needle (Fig. 4). Needle advancement was checked every 1–2 mm depth, and we aimed to keep contact with the vertebral body as much as possible and slipped along the vertebral body to ensure correct placement. When the required depth was achieved, an A-P view was obtained to confirm the correct position of the needle tip no deeper than the mid-pedicular position. After suction, 1 ml of iohexol (180 mgI/ml) over 20 s was injected to ensure proper needle placement (Figs. 5, 6). For the anesthetic block, we used a mixture of bupivacaine 2 mg/kg with dexamethasone 0.2 mg/kg, confirmed by adequate spread of the dye by fluoroscopy (Fig. 7).

Fig. 1
figure 1

A-P view of lumbar vertebrae

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Fig. 2
figure 2

Oblique view with the end of the transverse process aligned with the anterior aspect of the vertebral body

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Fig. 3
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Needle introduced in tunneled vision

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Fig. 4
figure 4

Lateral view obtained to determine the depth of the needle

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Fig. 5
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Proper needle position, with dye (iohexol) injection to confirm accurate needle position in the antero-posterior (A-P) view

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Fig. 6
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Proper needle position, with dye (iohexol) injection to confirm accurate needle position in the lateral view

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Fig. 7
figure 7

Adequate dye spread after injecting the local anesthetic and steroid

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Injectate Volume Calculation

There are no established guidelines recommending the volume of injectate for this technique in pediatrics. Therefore, we used the guidelines for epidural dosing in pediatrics as a proportional reference. If we know that the lumbar epidural volume for pediatrics ranges from 0.25 to 0.0.5 ml/kg [11], we agreed to have a reduced volume for our case because the point of injection is not in a closed space like the epidural space. We injected a total volume of 2 ml, confirmed by the dye spread after injection, which was satisfactory with no evidence of epidural, intravascular, or lateral spread.

Radiation Dose

The radiation dose from recorded images and number of images recorded during the procedure were reduced to attain optimum clarity and quality of the images without ignoring the safety of the patient or the procedure.

Accumulated values measured by the machine were as follows: radiation time: 00.00.38 (38 s); dose area product (DAP): 12.67 µGy∙m2 (reference air kerma (mGy) 0.30.

At this point, the patient was turned in a supine position. The general anesthesia was terminated, and the LMA was removed after securing adequate reflexes. The lower limb temperature was checked upon arrival in the recovery room. An elevation of 2.9 °C was achieved, confirming an adequate sympathetic block. The hemodynamic values showed no significant differences. The mother was invited to join the daughter in the recovery room. The first general impression was that there was no allodynia, and the child was trying to extend her knees. After complete recovery, she was discharged from the recovery room, and after another 3 h, she was discharged, and referred to the pediatric rehabilitation department.

Follow-up

After 3 and 8 weeks, in a follow-up visit, the parents reported overall improvement. Pain and allodynia were reported to be improved by 80%, and 70% respectively, with noticeable improvement in sleep, mood, and activity. On examination, there was almost no allodynia. However, the knee was still contracted. The patient had gained 900 g of body weight at the 3-week follow-up visit, and the parents reported a better appetite. During a follow-up phone call 4 months later, the patient’s mother expressed her satisfaction for the significant improvement of pain and sleep, indicating these were no longer issues. However, she did note a delay in rehabilitation progress. On a positive note, the patient can now step over her feet, has started walking, and is able to bear weight on her affected knee.

Discussion

CRPS has been reported in literature before the age of 3 years [3]. This case is the first reported in the literature to be diagnosed at such a young age (18 months). To the best of our knowledge, the youngest previously described case of CRPS was an upper limb ailment in a two-and-a-half-year-old girl [3]. Diagnosis of CRPS early in life is extremely difficult, as the patients cannot communicate. So, there is no real description of their pain. A previous publication stated that the psychological and functional effects of CRPS are more intense in children than in adults, [12] which is consistent with this case. However, the literature on the criteria for CRPS diagnosis is not solid, especially in children. Based on the Budapest Criteria [13], our patient suffered from continuous pain disproportionate to any stimulation. Symptoms and signs included sensory alterations, allodynia, sudomotor, edema around the knee, and motor abnormalities, made evident by the decreased range of movement and motor dysfunction. Hence, there was no other possible diagnosis explaining the signs and symptoms better.

Measurement of pain or functional impairment is usually based on self-reporting, even in children. However, it was not possible in our patient. Any instrumental investigation (like EMG) was impossible in this case because, as previously stated, it would have required general anesthesia, which would have altered the result. However, X-rays and MRI of the right knee were performed and resulted negative.

The LSB technique itself was not different from the technique used in adults, but we had to make some adaptations to meet the challenges of this very young patient. Among them, there was the choice of the needle length, and the needle advancement that was done very prudently (advancements of 1–2 mm max). As far as we know, this is the first report describing in detail the LSB technique at such a young age.

Radiation exposure was a major concern, as there were no previously described fluoroscopy-guided pain management interventions at such a young age and at very low body weight. Due to the limited data from clinical practice on calculating radiation doses for this age group, particularly those with low weight for age, and in comparison to other procedures and radiological examinations performed on the pediatric population (such as colonography and micturating cystourethrography), the ALARA (As Low As Reasonably Achievable) principle was adopted, as recommended by the Society of Pediatric Radiology [14,15,16]. Radiation dose from the recorded images and the number of images recorded during the procedure were reduced to attain optimum clarity and quality of the images without ignoring the safety of the patient. By comparing the radiation dose area product (DAP) of our patient to data published in similar procedures, our data were on the low limits, ensuring adequate protection [14, 16]. Lead protection could not be applied because the weight of any lead protective tool was too heavy for such a small patient.

Squaring of the images of the vertebral bodies was difficult due to the lack of ossification of the apophyses that is not completed until adulthood. The epiphyseal plates appeared not squared and soft [17]. Also, because of the small size of the patient, having the minimal cephalad or caudad tilt in the C-arm angle caused a significant change in angle of the image. Considering we were concerned about radiation exposure of such a small patient, we agreed to use the least number of images to achieve a reasonably accepted visualization, as previously described.

Ketamine injection was an addition to our management. It has contributed to the induction of general anesthesia, and it might have contributed to the management of CRPS, as suggested in previous reports on adults [7]. We commonly use it in our unit for pediatric pain management interventions that require light general anesthesia or monitored anesthesia care. It is known to be an NMDA receptor antagonist [8]. In addition, ketamine acts on other non-NMDA pathways that affect pain and mood regulation. It acts as an antagonist of nicotinic and muscarinic cholinergic receptors. It also blocks sodium and potassium channels. Ketamine activates high-affinity D2 dopamine receptors and type 1 voltage-gated calcium channels, promotes γ-aminobutyric acid A (GABA-A) signaling, and enhances descending modulatory pathways. There are several studies on the effectiveness of intravenous ketamine infusion for the management of CRPS in the adult population including reports of resistant cases [7, 8].

The calculation of dose and volume of local anesthetics was a further challenge, especially when it comes to injection volumes for an intervention at such a young age, but we have tried to link previous case reports with comparisons of the volumes used in epidural injections for children [18,19,20]. A number of previous reports of the technique have been conducted in children aged 8 to 12, and stated their maximum volumes being of 6 ml [18].

The psychological effect of CRPS on children is generally very strong and it was very evident in our case. This factor received great attention and we did our best to make the experience of the intervention acceptable. The child and mother separation was not carried out until the patient was under GA, as recommended in the literature [20]. The most overwhelming problem in this case was the level of functional and psychological disability of such a fragile patient. So, the intervention here was not only to save her limbs but also to guarantee a better quality of life.

Limitations

A limitation in our case study was that none of the established indicators or metrics for allodynia were possible to assess allodynia in this specific patient because of the considerable intensity of pain, her vulnerability, and the absence of direct communication. We relied exclusively on the observations made by the patient’s mother. However, we were able to identify the affected region of allodynia (which was as basic as sensitivity to light touch) and utilized the FLACC scale to evaluate the level of pain at rest prior to treatment, which was recorded as being as high as 8 out of 10.

Conclusions

CRPS can be diagnosed very early in life. For management, lumbar sympathetic blocks have also proven useful at a very young age when performed with extreme caution, particularly if other non-invasive measures have failed. Until clear guidelines for doses, techniques, and procedures are established, general rules should be followed, and all protective measurements must be taken.