A rare challenge: A patient with progressive fibrodysplasia ossificans and acute ischemic stroke treated with mechanical thrombectomy.

Summary

Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification. Here, we briefly describe the case of a 56-year-old male with known FOP and acute ischemic stroke that underwent mechanical thrombectomy with conscious sedation. Treating physicians should be aware of special medical considerations to prevent flare-ups and inflammation that result from any tissue injuries in this disease. Mechanical thrombectomy is a challenging scenario because general anesthesia and injections should be avoided in these patients. The treatment is still preventive and supportive, but this is the first report of the procedure in a patient with FOP.

1. Introduction

Fibrodysplasia ossificans progressiva (FOP) also called myositis ossificans progressiva or “stone man disease”, is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon [1]. The prevalence is approximately 1 in 2 million with no sex, racial, ethnic, or geographic predisposition [2]. FOP patients have increased anesthetic risks due to restrictive lung disease, fused cervical vertebrae, restricted oral access, and abnormal cardiac conduction and biopsies or surgery usually precipitate aggressive ossific reaction in the soft tissues [2]. Injections are usually contraindicated because they precipitate flare-ups with significant swelling and inflammation as do arterial punctures. For surgery or interventional procedures, a carefully designed anesthesia plan is crucial [1]. Ischemic stroke is uncommon in these patients maybe because they can succumb earlier from cardiopulmonary complications of severe restrictive chest wall involvement [3].

2. Case description

A 56-year-old right-handed male with FOP with known mutation in activin receptor IA (ACVR1), was transferred to the emergency department due to sudden right-sided hemiparesis and global aphasia. On admission he was aphasic with deviated gaze and right-sided hemiparesis and hemianesthesia (National Institute of Health Stroke Scale score: 13 points). Multimodal CT showed hyperdensity along the left middle cerebral artery (MCA) and hypoperfusion restricted to MCA territory (ASPECTS score: 7). He received intravenous Tenecteplase 18 mg (0.25 mg/kg) and was transferred to the Angio suite. The patient was placed in supine position on the angiography table. Trans-Radial approach was preferred in this patient due to his condition (superficial location, no nearby other anatomic structure and less soft tissue injuries could be avoided in order to prevent flare-ups). Before puncture, 2 mL of 1% lidocaine without epinephrine was infiltrated in the subcutaneous tissue over the radial artery. General anesthesia was avoided in this patient because of his previous cervical spine fusion, jaw motion limitations, sensitive airway and risk of an obstructing neck flare in FOP patients. Conscious sedation was administered by an attending anesthesiologist using the protocol for conscious sedation with 1 mg/kg propofol as the loading dose followed by a maintenance dose of 2–4 mg/kg per hour with propofol and remifentanil, 0.2 μg/kg per hour. After placement of a 6-F in a right radial line, angiography confirmed an occlusion of the MCA (Fig. 1, A) with a Thrombolysis in Cerebral Infarction (TICI) grade 0 and Qureshi grading scheme 3-A, mechanical thrombectomy (MT) with Preset retriever was performed resulting in a successful reperfusion (TICI 3 and Qureshi grade 0), after two passes and 4.5 h after the onset (Fig. 1, B). The patient was transferred to the stroke unit for monitoring after the procedure. His neurological exam improved, and he was without neurological symptoms by day 2. Steroids were maintained during the hospital stay (40 mg of methylprednisone IV) with progressive reduction to 15 mg P.O. Heterotopic ossification could be seen on X-Ray and CT scan that were performed because the patient had pain in the hips (Fig. 2, A and B). Three months after the onset, the patient was in the same situation as before the acute stroke.

Fig. 1.

Digital angiography with transradial approach: A, occlusion in left M2 segment (Middle Cerebral Artery, white arrow). B: successful reperfusion after two passes with mechanical thrombectomy (Thrombolysis in Cerebral Infarction grading scale 3).

Fig. 2.

A: Simple X ray left leg, lateral view: ossification of muscle, tendon and ligaments of multiple sites all along the tendons and muscles of the thigh (green arrow). B: CT SCAN, axial view: gross heterogeneous muscle calcifications located in the adductor muscles, more evident on the left side (yellow arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

3. Discussion

Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic condition characterized by congenital malformations and progressive heterotopic ossification (Fig. 2, A and B). Flare-ups are episodic and immobility is cumulative. A common mutation in activin receptor IA (ACVR1), a bone morphogenetic protein (BMP) type I receptor, exists in all sporadic and familial cases with a classic presentation of FOP [4]. Approximately 97% of individuals with FOP have this recurrent mutation. Here, we briefly review the acute peri-procedural management of this patient. Current recommendations include highly skilled FOP-aware anesthesiologists and FOP patients should be consulted pre-operatively except in emergencies [1].

In AIS patients during MT the goal of anesthesia management is to increase patient comfort, facilitate treatment, reduce patient motion, and reduce the risk of complications. The two most used anesthetic options are complete general anesthesia (GA) or a more moderate level of conscious sedation (CS). Both routes have theoretical advantages and disadvantages. GA is thought to allow superior recanalization through immobilization of the patient, reducing risk of image degradation and reducing the risk of potential wire or catheter-induced vessel damage [5]. Some studies have observed a benefit to CS regarding mortality and long-term neurological outcomes [6] but ultimate decisions could change depending on patient characteristics. FOP patients may present with submandibular swelling, a medical emergency, and requires intensive precautionary measures to avoid catastrophic clinical deterioration. Flare-ups often result from soft tissue injuries and because of the potential damage in the submandibular region and jaw, CS was preferred in this case. In patients who present with fusion of the cervical vertebrae, limited mouth opening, or ankylosis of the temporomandibular joint, the oral access for endotracheal intubation is not always possible, an awake fiberoptic nasotracheal intubation under light sedation is recommended [1]. In this case, a light sedation was enough to keep the patient relaxed for the procedure. Routine monitoring was performed (ECG, non-invasive blood pressure, pulse oximetry, end-tidal CO2, and temperature) and an extra dose of intravenous steroids were administered (60 mg of methylprednisolone). The trans-radial access was preferred, the technique has been successfully used and described in a variety of cerebrovascular interventions, including MT [7]. It should be considered in those scenarios in which trans femoral access could be dangerous or harmful, like our patient. The forearm can be kept in mid-prone position right next to the body, which reduces discomfort and stress, because it could be more ergonomic. Vasospasm and occlusion in radial access is a potential complication but it didn't occur in our case (4%–20% of the procedures) [8]. The intervention was successful with minimal injury in soft tissues. Concerning peripheral lines, patients with FOP can tolerate intravenous access, but it's critical for the procedure to be performed in as gentle and minimally invasive manner as possible. Superficial IV access and venipuncture are acceptable but traumatic IV's must be avoided, which sometimes is not possible in the setting of emergency departments, everything in order to prevent heterotopic ossification.

4. Conclusion

There are no cases of a patient with FOP undergoing MT in the literature (according to a search for relevant articles on PubMed). The challenge in acute stroke management of patients with FOP involves proper management of the medical procedure (sedation, airway obstruction, limited movements, minimal traumatic procedures and use of steroids). Patients with FOP must be managed with specific precautions to prevent flare-ups and ossification. The feasibility of MT in FOP patients cannot be determined based on this single case, despite its favorable outcome. Nonetheless, it indicates that MT, with adequate cautions, can be used to treat acute stroke in this complex condition.

Funding

None.

CRediT authorship contribution statement

Antonio Cruz-Culebras: Conceptualization, Methodology, Writing – original draft, Investigation, Validation, Writing – review & editing.

Declaration of Competing Interest

The authors have no conflicts of interest to disclose.