1 Introduction

Rare lower extremity orthopaedic injuries, such as simultaneous bilateral hip fractures, are commonly associated with seizure disorders.^1–7 Episodes of uncontrolled violent muscle contractions seen in epileptics and seizure patients cause atypical stress on the bones and joints, resulting in injury.^4,8–12 It is estimated that 30%–35% of epileptic patients will experience a seizure-related injury during their lifetime.^5,13–15 Of those who present to the emergency department (ED) for a seizure episode, approximately 14% will have a secondary injury.^5,15 Furthermore, anti-epileptic medications used in the management of seizure patients is known to have deleterious effects on bone health and may increase their susceptibility to injury and recurrence.^16,17 Careful assesment for skeletal injury should therefore be performed when evaluating seizure patients in the ED.⁵

Despite the established association between seizure disorders and lower extremity injuries, there is a paucity of knowledge in the literature regarding the orthopaedic management of these patients. No standardized, evidence-based guidelines are currently available for perioperative care, as seizure-associated skeletal injuries are considered rare and complex.¹⁸ Given the various nuances related to epilepsy and anti-epileptic medication, a specialized approach to surgical and post-operative treatment should be implemented to mitigate complications and future recurrence.

The following investigation is a systematic literature review that describes the common lower extremity injuries identified in epileptic and seizure patients and the surgical and non-surgical intervention performed in the management of these patients. Specific focus is placed on the relationship between seizure episodes and lower extremity injury, surgical techniques performed to fit the patients’ condition and specific injury, and functional outcomes after intervention.

2 Methods

PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), Embase (https://www.embase.com/) Cochrane (http://www.cochranelibrary.com/), Scopus (https://www.scopus.com/), and Web of Science (https://apps.webofknowledge.com/) databases were systematically queried for studies involving orthopaedic lower extremity injuries in epileptic and seizure patients. The search syntax used included the keywords “Orthopaedic”, “Fracture”, “Fall”, “Injury”, “Dislocation”, “Periprosthetic”, “Spine”, “Vertebrae”, “Vertebral”, “Osteoporosis”, “Prosthetic dislocation of total joint”, OR “Arthroplasty”, AND “Status epilepticus”, “Seizure”, “Convulsion”, OR “Epilepsy”. The search was limited to the English literature, and the retrieved articles’ titles and abstracts were examined and checked for eligibility. Full-text publications and abstracts describing lower extremity injury resulting from seizure or prior history of epilepsy in at least one patient were selected for further analysis. Comments, editorials, errata, corrigenda, and responses, were excluded, as were non-human investigations.

All data were independently abstracted by three investigators (WWY, LGP, and OK) according to the inclusion criteria. Information retrieved from each publication encompassed the first author's last name, enrolled patients' number, sex, age, type and location of injury, reason for injury, comorbidities, medications, surgical technique, surgical complications, and functional outcomes at last follow-up.

3 Results

A flow diagram recapitulating the retrieved articles’ screening and selection processes is depicted in (Fig. 1). The preliminary literature search syntax yielded a total of 108825 articles, 36477 of which were indexed in at least two repositories. Of the remaining 36477 publications, 7366 non-English or non-human studies were excluded, as were 28880 articles that did not meet title and abstract eligibilities, including commentaries, errata, corrigenda, editorials, and responses. Of the remaining 231 articles, 119 were deemed irrelevant to our study. After a duplicate full-text review and reading, 112 publications met the eligibility criteria for qualitative synthesis, while 12 full text articles and abstracts were eligible for quantitative synthesis and included for further in-depth analysis (Table 1).

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Fig. 1 The study's PRISMA flow diagram and search strategy.

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Of the 13 patients enrolled, there were 10 (76.9%) and three (23.1%) males and females, respectively, with a mean age of 39.3 years (range, 11 months to 82.0 years). Bilateral femoral neck fractures were identified in seven (53.8%) cases, while bilateral acetabular fractures were found in two (15.4%) patients, along with one (7.7%) bilateral talar avulsion fracture, one (7.7%) unilateral right femoral neck fracture, one (7.7%) bilateral supracondylar femur fracture, and one (7.7%) unilateral right supracondylar femur fracture respectively. Evidence of fracture was reported in all 13 cases. Surgical intervention was performed in eight (61.5%) cases while non-surgical conservative management was used in five (38.5%) patients. Postoperative follow-up was reported for 10 (76.9%) patients and averaged 13.5 months (range, one month to 36 months).

In all 13 cases, the cause of lower extremity injury was attributed to a seizure episode. Eight (61.5%) of these cases were identified as tonic-clonic seizures, two (15.4%) cases were reported as unspecified epileptic seizures, while a series of tonic seizures were described in two (15.4%) patients. Postnatal hypoxic encephalopathy induced seizure was identified in one (7.7%) patient. A prior diagnosis of epilepsy was reported in nine (69.2%) patients, while other co-morbidities include mental retardation, chronic renal failure, diabetes mellitus, hypertension, coronary vascular accident, childhood meningitis, osteopenia, osteoporosis, Alzheimer's disease, Parkinson's disease, cytomegalovirus embryopathy, and Lennox Gastaut Syndrome were also reported. Anti-epileptic medication therapy was reported in seven (53.8%) patients including gabapentin, primidone, phenytoin, valproic acid, sodium valproate, carbamazepam, lamotrigine, vigabatrin, clobazam, clonazepam, and phenobarbital. Seizure attributed to medication non-compliance was identified in 4 (30.8%) cases.

Of the eight cases referencing surgical intervention (Table 2), closed reduction and internal fixation with screw placement (three [23.1%]), bilateral hip hemiarthroplasty (two [15.4%]), bilateral total hip arthroplasty (one [7.7%]), open reduction and internal fixation via the Smith-Peterson technique, (one [7.7%]), and bilateral dynamic hip screw osteosynthesis (one [7.7%]) were utilized for fracture management. In the five non-surgical patients, conservative management including non-weight bearing, fixed ankle walking boots, leg cast, physical therapy and rehabilitation, and analgesia was used. In all eight cases involving femoral neck fractures, surgical intervention was performed. Non-surgical intervention was utilized in the management of acetabular, supracondylar femur, and talar fractures. Intra- and post-operative complications (Table 2) were reported in 23.1% (three of 13) of patients, with appropriate management and satisfactory outcomes achieved in two of the three cases. The remaining patient had persistent issues with ambulation likely attributed to concomitant neurological damage from postnatal hypoxic encephalopathy. Functional outcomes were reported for 11 (84.6%) cases with 10 (90.9%) patients reporting favorable outcomes including restored ambulation and range of motion, pain free with full weight bearing, fracture healing, and no evidence of avascular necrosis (AVN) reported. As mentioned, one patient had issues with ambulation post-operatively.

4 Discussion

The management of epileptic patients can be challenging due to various complications secondary to seizure episodes. Violent convulsions can lead to musculoskeletal injuries, especially in the extremities, causing significant functional impairments, increasing their morbidity.^12,19 Simultaneous bilateral hip fractures are of particular interest as they are less common among the general population, and are almost exclusively associated with seizures, high impact trauma, or electroconvulsive therapy.^3,4,10,11 Osteoporosis, osteomalacia, renal osteodystrophy, hypocalcemia induced contractions, tumor growth and metastasis, and hormone disorders have also been implicated in bilateral femoral neck fractures, especially in the absence of major trauma.^3,4,9,10 Powerful and forceful muscle contractions in seizure episodes cause a forced hip flexion and abduction that creates an impingement of the femoral head on the acetabular rim. The resulting levering effect on the neck of the femur paired with the force from consecutive muscle contractions leads to femoral neck fracture.^3,20,21 Conversely, if the hip is adducted at the time of convulsion onset, muscle contractions inducing further adduction places pressure on the medial acetabular wall through the femoral head. Continuous contractions lead to fracturing of the medial wall and dislocation of the femoral head through the site of acetabular fracture.^3,20,21 Specifically, violent contractions of the pelvic-trochanter and proximal thigh muscles causing forces directed toward the groin, are implicated in both bilateral femoral and acetabular fractures in seizure patients.^{6,9,11,22–24} As a result, patients lose significant mobility in their hips, experience variable levels of pain, and have difficulty with ambulation when left untreated.

The current systematic review of 13 individuals identifies the common lower extremity injuries found in epileptic and seizure patients, describes the interventions used for various injury types, and identifies any complications with functional outcomes. In the eight cases of femoral head fractures resulting from convulsions, 87.5% were bilateral fractures and cases were predominantly seen in males (75.0%). Closed reduction with internal fixation and bilateral hip hemi- or total-arthroplasty were the most frequent surgical techniques performed (five of eight [62.5%]). Although the functional outcomes after intervention were satisfactory, as evidenced by 90.9% (10 of 11) of patients reporting adequate mobility and function, over a quarter (three of 11 [27.2%]) still described mild issues with pain, ambulation, and range of motion (ROM) deficits. One patient had a 15-month post-operative Harris Hip Score (HHS) of 85 on the right hip and 87 on the left hip, suggestive of very mild deficits after a closed reduction with internal fixation of a bilateral femoral head fracture.⁴ However, the patient had good bone joining, no issues with ambulation or weight bearing, and no evidence of AVN.⁴ Similarly, one patient had a Postel-Merle d'Aubigne (PMA) score of 17 after a bilateral total hip arthroplasty suggestive of minor deficits as well.⁶ Finally, Atmaca et al. describes one patient with persistent post-operative ambulatory issues after a Smith-Peterson approach open reduction and internal fixation was performed on a unilateral right femoral head fracture.² At 18-months follow up, the patient experienced a contralateral left hip dislocation likely attributed to muscle imbalance but showed no signs of AVN on the right hip.² These ambulatory issues may not be fully related to the seizure induced hip injury as the patient had neurological damage from postnatal hypoxic encephalopathy at birth.² Our findings suggest that current interventions are effective in restoring shoulder ROM to some extent, but additional consideration should be given to further improve residual movement deficits and prevent recurrence as a complication of epilepsy.

Poor bone health is commonly associated with epilepsy and anti-epileptic drug (AED) use.^{16,17,25–29} The incidence of bone fracture in epileptic patients is reported to be two to six times higher than the general population and the prevalence of low bone mineral density (BMD) is approximately 80% in those with chronic epilepsy.^16,30,31 Epileptic patients may have weakened bones at baseline due to various restrictions in physical activity, leading to greater susceptibility for fractures during convulsive episodes. The deleterious effects of AEDs on bone metabolism may lead to decreased bone density, further increasing the risk of fracture in epileptic patients. The adverse effects of these medications on bone can be attributed to the enhancement of Vitamin D metabolism to its inactive metabolites by the induction of the hepatic cytochrome 450 (CYP450) by various AEDs.^16,26–28 Specifically, carbamazepine, phenytoin, valproic acid, primidone, and phenobarbital all promote the activity of CYP450, resulting in the inactivation of Vitamin D and the decrease of calcium absorption.^16,26–28 The resulting hypocalcemia can trigger parathyroid (PTH) release, causing drug-induced hyperparathyroidism with increased bone catabolism.^16,26 Certain AEDs including carbamazepine, lamotrigine, and gabapentin have demonstrated modulatory effects on primary bone cells, leading to the inhibition of osteoblast and osteoclast production and maturation.¹⁷ These effects significantly impair bone remodeling and lead to poor bone health in epileptic patients.¹⁷ Osteoporosis, osteomalacia, and rickets have therefore been linked to chronic AED use, placing patients at increased risk for fracture.^17,26,27,29 When determining the appropriate management for epileptic patients with secondary musculoskeletal injuries, careful assessment of the individual's bone health and the severity of their seizure disorder should be considered prior to prescribing anti-epileptic medication. In certain cases, medications can adversely contribute to fracture risk and injury recurrence, especially in those with decreased bone density, and may need to be avoided.

Patients with a suspected seizure-associated lower extremity injury should have an anteroposterior (AP) radiograph of the pelvis performed immediately to confirm the diagnosis. Emergent internal fixation followed by either open or closed reduction are done in cases of bilateral femoral neck fractures.⁴ Performing internal fixation early prevents complications associated with vascular compromise, specifically AVN. Displaced femoral neck fractures, characterized as Garden Type 3 or 4, are of particular concern for AVN and can occur in up to 40% of cases.^4,32–34 In a meta-analysis by Lu-Yao et al., the incidence of AVN in patients with displaced fractures was reported as 16% while the incidence of non-union was 33%.^9,35 Risk of AVN is further increased by delays in internal fixation in addition to non-union or malunion, especially in the pediatric population.^2,4,36–39 Magnetic resonance or bone scintigraphy should be used to evaluate for evidence of AVN after femoral neck fixation.⁴ Early mobilization and weight bearing after surgery may improve clinical and radiologic outcomes by enhancing the restoration of blood supply to the bone and soft tissue and providing nutrition to the articular cartilage, thus avoiding post-operative complications.^9,40 Therefore, when patients with a prior history of epilepsy and lower extremity complaints present to the ED, a diagnostic protocol for seizure patients should be in place to ensure appropriate diagnosis of secondary fractures, as delays in management can lead to poor functional outcomes and permanent impairment.

Although systematically conducted to encompass all subjects with lower extremity orthopaedic injuries and a history of epilepsy or seizure disorder, our analysis carries some limitations. Pooled investigations were heterogenous and failed to document specific details regarding patient follow-up, surgical techniques, medication therapy, and clinical outcomes. However, with a comprehensive and in-depth analysis of all available reports in the current literature, our findings advance the current knowledge of lower extremity injuries associated with seizure disorders and the management of rare injuries in the field of orthopaedics.

5 Conclusion

Seizure patients with musculoskeletal complaints require unique consideration to accurately identify injuries and a specialized approach to treatment may be necessary to accommodate the nuances of their condition. Currently, the majority of lower extremity injuries in epileptic patients are managed in the same manner as those without a history of seizures. The lack in standardized diagnostic protocol and evidence-based perioperative guidelines and the deleterious effects of anti-epileptic medications on bone health are of particular concern. Improvements in diagnosis, surgical techniques, and medication management should therefore be made in an effort to minimize functional deficits and prevent injury recurrence. A specialized approach, including an established guideline for diagnosis and treatment, should be established to optimize clinical outcomes in lower extremity injuries secondary to seizure.

Funding statement

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.