Article Text
PDF
Abstract
Background Paraplegia is a rare complication of spinal anesthesia.
Case presentation We report a case of a 68-year-old man who developed postoperative paraplegia and hypoesthesia after spinal anesthesia for an otherwise uncomplicated transurethral resection of the prostate. Acute transverse myelitis was diagnosed based on urgent MRI. A prior history of similar though less severe neurological symptoms after obinutuzumab treatment for follicular lymphoma suggested a potential causative role for obinutuzumab, a novel monoclonal antibody that has not been associated with such devastating neurological side effects yet. High-dose steroid treatment partially attenuated the symptoms, but debilitating hypoesthesia and motor deficit remained present 3 months postoperatively.
Conclusion The presented case warrants caution when performing neuraxial anesthesia in patients on monoclonal antibody therapies.
- injections
- spinal
- drug-related side effects and adverse reactions
- neurotoxicity syndromes
- postoperative complications
Statistics from Altmetric.com
- injections
- spinal
- drug-related side effects and adverse reactions
- neurotoxicity syndromes
- postoperative complications
Introduction
Major complications of central neuraxial blocks are rare, with an estimated prevalence of permanent neural injury ranging from 0.002% to 0.004% and from 0.0007% to 0.0018% for paraplegia or death.1 In about two-thirds of patients presenting with neural injury after central neuraxial blocks, symptoms resolve fully over time and usually within the first 6 months. Common causes of neurological damage include direct needle trauma, vascular injury, spinal ischemia, or neurotoxicity from local anesthetics, adjuvants, or antiseptic agents.2 3
We report a case of postoperative paraplegia and hypoesthesia following spinal anesthesia for transurethral resection of the prostate (TURP). MRI showed signs of acute transverse myelitis, possibly initiated by prior intravenous treatment with obinutuzumab (Gazyvaro) for lymphoma. High-dose steroid treatment partially attenuated the symptoms. Three months postoperatively, the patient still suffers from debilitating hypoesthesia and motor deficit. The patient consented in writing to report this case.
Case report
A 68-year-old man underwent a redo TURP procedure to treat persistent urinary retention. A first TURP procedure was uneventfully under spinal anesthesia 2 months prior to the redo procedure, but insufficiently alleviated the patient’s urinary symptoms. His medical history further included follicular lymphoma stage III, treated with intravenous immunochemotherapy obinutuzumab-bendamustine. After induction chemotherapy 2 years prior to the scheduled TURP procedure, complete metabolic remission was achieved. Obinutuzumab maintenance treatment was subsequently administered intravenously every 2 months, with the last treatment 3 weeks prior to the surgery.
A preoperative anesthesiological consult revealed a strong preference of the patient towards neuraxial anesthesia over general anesthesia. Routine preoperative blood tests showed a mild normocytic anemia (hemoglobin 11.9 g/dL), mild thrombocytopenia (104,000/µL) and normal kidney function, as well as clotting tests within the normal ranges. The patient’s file showed no documentation or radiological evidence of neurological compromise. Hence, no contraindications for spinal anesthesia were identified.
On arrival in the operating theater, an intravenous line and standard monitoring was placed. The patient’s skin was disinfected using chlorhexidine 0.5% in alcohol, and after a sufficiently long drying period, spinal anesthesia was uneventfully performed at the L4-L5 level using a 27G Whitacre needle. Hyperbaric bupivacaine 0.5% 2 mL was injected. The procedure was successful on the first attempt and no paresthesiae were elicited. Surgical anesthesia was obtained up to the T10 dermatome and surgery was uneventful. The patient remained hemodynamically stable throughout the entire TURP procedure, which was not difficult, nor did the surgeon use excess amounts of infusion fluids or hypotonic fluids.
Four hours after surgery, the attending recovery anesthetist noted that the patient’s motor functions had not yet returned. Clinical examination revealed complete paraplegia and areflexia of the lower extremities, as well as hypoesthesia. A blood sample showed sodium levels of 135 mmol/L and potassium of 3.7 mmol/L, excluding postoperative electrolyte abnormalities. Urgent CT scan of the lumbar spine did not show any significant changes. A subsequent full spine MRI scan revealed a pathological T2-weighted hyperintense signal in the dorsal spinal cord, starting at level T6 and ranging to the conus medullaris, consistent with acute transverse myelitis (figure 1). Differential diagnosis at this stage included local anesthetic or chlorhexidine neurotoxicity, spinal ischemia, and reactive myelitis following immunotherapy. Further in-depth questioning of the patient revealed undocumented similar, though less severe transient symptoms of hypoesthesia and loss of muscle force after several of his previous obinutuzumab treatments. His current urinary retention had also appeared since his recent immunotherapy. High-dose steroid treatment was initiated, which within days diminished the hypoesthesia with partial recovery of the motor functions. The patient refused to undergo a diagnostic lumbar puncture. A follow-up MRI after 1 week showed an unchanged image of myelitis. After a 3-week hospital stay, the patient was discharged to a rehabilitating facility. Three months later, the patient still suffers from hypoesthesia and a severe motor deficit of the lower limbs.
T2-weighed sagittal MRI image showing a pathological hyperintense signal (yellow arrows) in the dorsal myelum starting at D6 and ranging to the conus medullaris.
Discussion
Paraplegia is a rare complication of neuraxial anesthesia, affecting approximately 0.7–1.8 adults per 100,000 procedures.1 Neurological damage is most often caused by direct needle trauma, severe hypotension leading to ischemia, vascular injury resulting in epidural hematoma, or neurotoxicity from the local anesthetic, adjuvants, or antiseptic agent.2–4 An urgent full spine MRI scan is essential to exclude causes such as an epidural hematoma, which warrants immediate surgical decompression.5–7
In this case, MRI revealed acute transverse myelitis, a rare condition consisting of acute to subacute inflammation of the spinal cord. It roughly affects one to five adults per million per year worldwide.8 Symptoms generally include motor and/or sensory deficits, depending on the involved descending and ascending spinal tracts.8 Etiologically, acute transverse myelitis has been associated with autoimmune or infectious diseases, vascular problems, certain drugs such as tumor necrosis factor-alpha inhibitors, sulfasalazine, chemotherapeutic and epidural anesthetic agents, or it can remain idiopathic. A lumbar puncture to investigate markers of inflammation in the cerebrospinal fluid may aid in identifying the underlying cause. Initial treatment consists of high doses of intravenous steroids, usually 1 g of methylprednisolone for 3–7 days.8–10
In-depth history of our patient revealed prior but undocumented episodes of neurological dysfunction after obinutuzumab (Gazyvaro) treatment, suggesting previously existing spinal cord damage. His urinary retention may also fit within the same clinical picture. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody and a relatively novel drug used for induction treatment and maintenance therapy of follicular lymphoma.11–13 It has gradually replaced rituximab as the monoclonal antibody of choice for this disease, due to its improved progression-free 3-year survival rates.11 12 14 Obinutuzumab, however, has also been associated with more adverse effects, most commonly consisting of infusion-related reactions, neutropenia, and leukopenia, but also more devastating adverse effects, such as progressive multifocal leukoencephalopathy (PML) and hepatitis B reactivation. These adverse effects occur almost twice as frequently as compared with rituximab.11 15
To our knowledge, no cases of transverse myelitis after obinutuzumab use have been reported.16 However, other monoclonal antibodies have been associated with transverse myelitis, as well as other important neurological side effects, including PML and demyelinating disorders. These side effects have been mostly described for tumor necrosis factor alpha-targeting monoclonal antibodies, including natalizumab, rituximab, alemtuzumab, and efalizumab.17–20 Hence, it is not illogical to presume that transverse myelitis may occur with obinutuzumab as well.
In the current case, the patient’s history raised the suspicion for obinutuzumab as possible causative agent of an a priori underlying transverse myelitis. Differential diagnoses included direct neurotoxicity and inflammation from local anesthetics and chlorhexidine, which have both been previously described in literature.21 Prolonged and high-dose local anesthetic agent administration has been associated with neurotoxicity. Nevertheless, low-dose local anesthetic neurotoxicity can transform subclinical pre-existing neurological conditions into clinically apparent neuropathies. This phenomenon is known as the ‘double crush syndrome’.22 Chlorhexidine toxicity, appears to be a less probable contributor in this case as a low concentrated solution was used and the patient’s skin was completely dry prior to skin puncture. A pre-existing spinal dural arteriovenous fistula (SDAVF) should also be part of our differential diagnosis. SDAVF, a rare lesion where a vascular shunt exists between a dural branch of a segmental artery and a radicular vein, results in venous hypertension and congestive myelopathy. Lumbar puncture causes neurological damage due to the decrease in cerebrospinal fluid (CSF) pressure which leads to acute ischemic aggrevation.23 24 However, the lack of CSF loss during spinal anesthesia makes this an unlikely scenario. Other potential causes of neural injury such as direct trauma, epidural hematoma, or ischemia due to hypotension are unlikely since the puncture was uneventful, the patient remained hemodynamically stable and the negative postoperative MRI imaging.
We therefore consider pre-existing subclinical transverse myelitis, potentially caused by obinutuzumab, to be the most likely origin of the patient’s symptoms, mostly by exclusion of other causes. It is unclear to what extent the use of spinal bupivacaine exacerbated the underlying inflammation. Further work-up was not possible as the patient refused a diagnostic lumbar puncture.
Patients receiving treatments with known deleterious neurological side effects such as monoclonal antibodies should be questioned and examined extensively prior to neuraxial anesthesia for pre-existing neurological problems. General anesthesia might be the safer option.
Conclusion
We present a case of paraplegia and hypoesthesia occurring after spinal anesthesia. The patient likely suffered from pre-existing neurological impairment, possibly caused by obinutuzumab used to treat follicular lymphoma. Spinal anesthesia may have exacerbated the spinal inflammation, leading to motor and sensory deficits. Caution is thus warranted when performing neuraxial anesthesia in patients using monoclonal antibodies, in whom we suggest extensive evaluation of pre-existing neurological symptoms.
References
Footnotes
Contributors AH: This author contributed to the conception and authorship of the article. LVD: This author contributed to the conception and authorship of the article. IL: This author contributed to the clinical care and authorship of the article. LD: This author contributed to the clinical care and authorship of the article. PBCVdP: This author contributed to the conception and authorship of the article.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.