Surgical treatment of medically refractory movement disorders is considered the standard of care. ^{Reference Rezai, Machado, Deogaonkar, Azmi, Kubu and Boulis1} Since its FDA approval in 2016 for unilateral thalamotomy, the Exablate device (InSightec Inc., Miami, USA) is increasingly utilized for medically refractory tremor. ^{Reference Elias, Lipsman and Ondo2} Moreover, recent trials have demonstrated its safety with bilateral treatment when performed in a staged approach. ^{Reference Kaplitt, Krishna and Eisenberg3} However, certain limitations for using this technology persist. Although MRI-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less, minimally invasive, ablative treatment, it targets deep brain structures and carries a nontrivial risk of hemorrhage. Like deep brain stimulation (DBS), patients on anticoagulants can create challenges for surgeons and anticoagulant use often limits their eligibility for MRgFUS. Current literature lacks clear perioperative anticoagulation guidelines tailored to the physiological characteristics and risk profile of MRgFUS procedures. To explore this limitation, we present a case report of a safe and effective MRgFUS thalamotomy on a patient with a factor V Leiden mutation on long-term anticoagulation and review the pertinent literature on brain ablation with focused ultrasound (FUS) in patients with anticoagulants.

A 63-year-old left-handed man presented for surgical treatment for his medically refractory essential tremor, which had affected his daily activities. He scored 15 out of 24 for his left hand on the motor and tasks components of the Essential Tremor Rating Assessment Scale, indicating a severe tremor. Previously, he had undergone bilateral ventral intermediate nucleus (VIM) DBS, which was later explanted due to infection. His past medical history included factor V Leiden mutation; he was on chronic warfarin therapy, having experienced deep venous thrombosis after stopping it for a spine surgery. Our institutional multidisciplinary team recommended surgery for his tremor with cautiously assessing and managing the risk. He opted against repeat DBS surgery but chose to undergo right VIM MRgFUS thalamotomy for his dominant hand tremor. After hematological consultation, a bridge treatment with enoxaparin was proposed. Warfarin was stopped six days preoperatively, and a twice-daily enoxaparin regimen was started. Enoxaparin was stopped 24 hours preoperatively. Right VIM MRgFUS thalamotomy was uneventful, which involved a total of 10 sonications, with the maximum temperature reaching 61°C (Figure 1A). Postoperatively, he experienced near-complete resolution of his left-hand tremor(Figure 2 A,B). A CT scan of the brain was performed the following day to rule out any bleeding, and enoxaparin was restarted along with warfarin. Enoxaparin was stopped once the international normalized ratio (INR) reached a therapeutic level. Before discharge, he did report numbness in the fingertips of his left hand. MRI and CT performed the next day demonstrated perilesional edema likely contributing to these symptoms, for which a short dexamethasone taper was prescribed (Figure 1 B). At an 18-month follow-up, the tremor control remained complete, with only mild residual paresthesia. Unfortunately, due to COVID-19 restrictions, he did not present for an in-person assessment.

Figure 1. (A) Immediate postoperative T2W MRI showing right thalamic ventral intermediate nucleus ablation. (B) Postoperative day 1 CT to rule out hemorrhage.

Figure 2. Left-hand drawing tasks (A) preoperative and (B) postoperative.

MRgFUS thalamotomy is a highly effective, incision-less, minimally invasive, ablative treatment for medically refractory tremor. Additionally, this technique eliminates risks associated with infection, hardware-related complications and CSF leakage. However, many patients are excluded from this treatment due to technical limitations related to undergoing MRI including MRI-incompatible devices and medical comorbidities such as coagulopathy. Efforts have been made to move beyond standard clinical practices with reports of MRgFUS performed in patients with MRI-compatible cardiac pacemakers, employing a 1.5 T MRI rather than a standard 3T MRI for FUS procedures. ^{Reference Ito, Fukutake and Yamamoto4,Reference Iacopino, Gagliardo and Giugno5} Unfortunately, literature on the safety of MRgFUS in patients with coagulopathy or on anticoagulants remains underrepresented. Although larger studies have demonstrated the relative safety of MRgFUS with a low side effect profile and no reports of hemorrhagic complications, ^{Reference Elias, Lipsman and Ondo2} the apprehension about potential hemorrhagic effects continues in patients on chronic anticoagulation. Unlike conventional neurosurgical procedures, focused ultrasound’s characteristics may lead clinicians to underestimate the importance of perioperative anticoagulation decisions, despite the lesion being intracranial and irreversible. Jeanmonod et al. reported an asymptomatic bleed at the target site during central lateral FUS thalamotomy for chronic neuropathic pain. ^{Reference Jeanmonod, Werner and Morel6} However, a recent retrospective study indicated that it may not be necessary to interrupt anticoagulant/antiplatelet therapy for patients undergoing MRgFUS for tremor treatment. ^{Reference Caston, Campbell, Rahimpour, Moretti, Alexander and Rolston7} Despite these findings, most centers continue to either exclude patients with coagulation issues or require them to pause anticoagulant usage. According to the American College of Chest Physicians (ACCP) guidelines, patients with a high risk of thromboembolism who are on chronic warfarin and require elective surgery may stop warfarin five days preoperatively, bridging with low molecular weight heparin (LMWH), which can then be discontinued 24–72 hours before surgery depending on the bleeding risk. ^{Reference Douketis, Spyropoulos and Spencer8} Warfarin should be resumed 12–24 hours postoperatively, provided there is adequate hemostasis and bridged with LMWH until INR becomes therapeutic. Nevertheless, this strategy can be associated with risks of bleeding, particularly intracranial, which can have serious implications. ^{Reference Douketis, Spyropoulos and Spencer8} Importantly, stereotactic brain surgery requires more caution than conventional brain surgery, where bleeding can be controlled due to open access.

Today, there are no standardized anticoagulation protocols for MRgFUS ablation of brain targets, which underscores the need to develop a consensus ensuring both patient safety and procedural efficacy. Our case highlights the feasibility of safe execution of MRgFUS thalamotomy in patients with congenital hypercoagulability on chronic anticoagulation. Patients with coagulopathies or on chronic anticoagulation have higher risks of complications as compared to patients with normal hemostasis. In this patient category, MRgFUS thalamotomy should be considered after a careful risk-benefit assessment and managed with a multidisciplinary team approach. By following standardized anticoagulation bridging guidelines for routine elective surgery, the bleeding and coagulation risks can be mitigated. Although our results cannot be generalized to all types of coagulopathies, we believe similar protocols can be successfully applied with close consultation from hematology. Further research is warranted to develop universal guidelines for MRgFUS use with patients who are taking chronic anticoagulation. We believe that guidelines similar to those from the ACCP for traditional, elective surgeries can be adopted to MRgFUS, allowing for greater access to patients who may be traditionally excluded from this procedure.