Are there recommendations for IV or PO methylprednisolone dosing for cauda equina syndrome?

Comment by InpharmD Researcher

Methylprednisolone regimens for management of cauda equina syndrome widely vary in dose and duration, and are primarily derived from case reports (see Tables 1-4). Treatment strategies mainly consist of intravenous administration, ranging from 250 mg to 1 g daily, with adjunct pharmacotherapy (e.g., oral prednisone, intrathecal methylprednisolone) provided, thus limiting consensus on the most optimal dosing for this patient population.

Background

Clinical trials evaluating the use of methylprednisolone in the management of spinal cord injuries have studied various dosage regimens. One of the first clinical trials, the National Acute Spinal Cord Injury Study (NASCIS 1, published in 1984), compared methylprednisolone given as a 100 mg bolus followed by 25 mg every 6 hours for 10 days versus 1,000 mg bolus followed by 250 mg every 6 hours for 10 days. No difference in observed improvements occurred between the high- and low-dose groups, but there was a significantly increased incidence of wound infections in the high-dose group (9.3% vs. 2.6%) as well as a slightly higher incidence of sepsis, pulmonary embolism, and death within 14 days. In the subsequent trial (NASCIS II, published in 1990), patients received methylprednisolone as a 30 mg/kg bolus followed by 5.4 mg/kg for 23 hours, which was found to produce similar effects on motor and sensory scores compared to naloxone 5.4 mg/kg bolus followed by 0.5 mg/kg/h for 23 hours and placebo. [1], [2], [3]

Trials following NASCIS II utilized the same methylprednisolone dosage regimen, except for the NASCIS III trial in 1997 which compared methylprednisolone regimens of 5.4 mg/kg/h for 24 hours and 5.4 mg/kg/h for 48 hours. Expert opinion recommends that although high-dose steroid treatment may be safe in other patient populations, caution should be exercised in the setting of acute traumatic spinal cord injury given the data from NASCIS. It should be noted that none of the described studies specifically evaluate patients with cauda equina syndrome, and in fact, two studies excluded such patients. It is unknown if the dosage regimens utilized in the described studies would be effective and safe in the setting of cauda equina syndrome. [1,4-6]

A 2004 case series evaluated 63 patients diagnosed with schistosomal myeloradiculopathy (SMR) over a period spanning 15 years at a university hospital in Brazil; 12 (19%) patients had cone and cauda equina syndrome. Laboratory findings revealed abnormal CSF profiles in 93.7% of patients, frequently characterized by elevated protein concentrations and pleocytosis, with eosinophils detected in approximately 57% of samples. Treatment involved high-dose corticosteroids (prednisone or methylprednisolone 500 mg q12h for 5 days followed by prednisone) initiated within 24 hours of admission, followed by praziquantel therapy after confirmation of active schistosomiasis. The therapeutic response was rapid, with improvement frequently observed within 48 hours of corticosteroid initiation. Favorable neurological outcomes, ranging from full recovery to partial recovery without functional limitations, were achieved in 60.3% of patients. However, 39.7% experienced persistent functional impairments, correlating with more pronounced medullary involvement. All (100%) of the patients with cauda equina syndrome demonstrated complete recovery, which was significantly better than patients with meduallary forms (p= 0.007). Of note, the route of administration for methylprednisolone was not provided in the article. [7]

A 2002 experimental study investigated the efficacy of methylprednisolone in mitigating neurophysiological and histopathological damage in acute cauda equina injuries using a rabbit model. The study induced injury by applying an aneurysm clip with a closed pressure of 192 grams to the cauda equina at the S2–S3 level for three minutes, taking care to preserve the dura. Neurophysiological assessment involved measuring nerve conduction velocity (NCV) pre-injury, immediately post-injury, and three weeks after injury, while histopathological features were examined in excised tissue samples stained with hematoxylin-eosin. Rabbits were divided into four groups: three treatment groups receiving methylprednisolone (30 mg/kg) at 8, 16, or 24 hours post-injury alongside continuous infusion for 24 hours, and an untreated control group. Results demonstrated a statistically significant recovery in NCV at three weeks in the group treated at 8 hours post-injury (p<0.05), while improvements in the 16- and 24-hour treatment groups were less pronounced. Untreated animals exhibited no recovery. Histological analysis revealed minimal edema, inflammation, and hemorrhage in the 8-hour treatment group, contrasting with more pronounced pathological changes in later-treated or untreated groups. These findings underscore the importance of early methylprednisolone administration in limiting the progression of secondary injury mechanisms, such as edema and inflammation, which compromise nerve root function. The evidence supports the neuroprotective effects of high-dose corticosteroids administered within a critical time window following acute cauda equina injury. [8]

References:

[1] Cheung V, Hoshide R, Bansal V, Kasper E, Chen CC. Methylprednisolone in the management of spinal cord injuries: Lessons from randomized, controlled trials. Surg Neurol Int. 2015;6:142. Published 2015 Aug 24. doi:10.4103/2152-7806.163452
[2] Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA. 1984;251(1):45-52.
[3] Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990;322(20):1405-1411. doi:10.1056/NEJM199005173222001
[4] Otani K, Abe H, Kadoya S, Nakagawa H, Ikata T, Tominaga S. Beneficial effect of methylprednisolone sodium succinate in the treatment of acute spinal cord injury. Sekitsui Sekizui. 1994;7:633-47.
[5] Pointillart V, Petitjean ME, Wiart L, et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord. 2000;38(2):71-76. doi:10.1038/sj.sc.3100962
[6] Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA. 1997;277(20):1597-1604.
[7] Lee DW, Kang S, Kim N. Recurrent Acute Disseminated Encephalomyelitis Presenting as Conus Medullaris Syndrome: A Case Report. Medicina (Kaunas). 2024;60(1):188. Published 2024 Jan 22. doi:10.3390/medicina60010188
[8] Gök A, Uk C, Yilmaz M, Bakir K, Erkutlu I, Alptekin M. Efficacy of methylprednisolone in acute experimental cauda equina injury. Acta Neurochir (Wien). 2002;144(8):817-821. doi:10.1007/s00701-002-0964-z

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Are there recommendations for IV or PO methylprednisolone dosing for cauda equina syndrome?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Tables 1-4 for your response.


 

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report

Design

Case report

Case presentation

A 56-year-old woman with a history of hypertension developed spinal subarachnoid hematoma (SSH) associated with aneurysmal subarachnoid hemorrhage (SAH). The patient presented with a severe headache and was diagnosed with SAH secondary to a ruptured middle cerebral artery aneurysm, which was treated with coil embolization. Nine days after the procedure, the patient developed severe lumbago with radiation to both legs.

Magnetic resonance imaging (MRI) revealed a hematoma extending from L5 to S2, characterized by iso-signal intensity on T1-weighted sequences and low signal intensity on T2-weighted sequences, suggestive of early subacute hemorrhage in the spinal subarachnoid space compressing the cauda equina.

The patient received conservative management with IV methylprednisolone (250 mg/day for four days), followed by a gradual taper of oral prednisolone (20 mg/day), resulting in complete recovery. Repeat MRI at one month demonstrated complete hematoma resolution with no recurrence.

Study Author Conclusions

Rapid subarachnoid bleeding from ruptured intracranial aneurysm may result in formation of SSH, and these cases are easily neglected due to limited knowledge and mild clinical symptoms. This case helps to raise awareness that though SSH is a rare comorbidity, a high degree of medical attention should be given to patients with acute sciatica symptoms following intracranial SAH.

 

References:

Ni H, Zheng Y, Lu S, et al. Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report. BMC Neurol. 2024;24(1):5. Published 2024 Jan 2. doi:10.1186/s12883-023-03404-2

 

Cauda equina syndrome after spinal anaesthesia in a patient with asymptomatic tubercular arachnoiditis

Design

Case report

Case presentation

A 14-year-old male developed cauda equina syndrome following spinal anesthesia performed during emergency debridement surgery for right foot cellulitis. The patient, who had no previous medical history suggestive of systemic illness, underwent spinal anesthesia with a 25G needle through the L3-L4 interspace. A total of 50 mg of 5% hyperbaric lignocaine, diluted to 2%, was administered intrathecally. The procedure (including intraoperative monitoring and sedation with IV midazolam) was uneventful, with a sensory block achieved at T10. Within four hours postoperatively, the patient experienced significant motor impairment, bilateral thigh paresthesias, urinary retention, and absent deep tendon reflexes, with no regression of the sensory block.

Subsequent MRI revealed clumping of cauda equina nerve roots, dural ectasia, myelitis, and intradural granulomas, leading to a diagnosis of tubercular arachnoiditis, confirmed by polymerase chain reaction testing for tuberculosis. Management involved the initiation of IV methylprednisolone (500 mg/day) and standard antitubercular therapy (isoniazid, rifampicin, pyrazinamide, ethambutol, and pyridoxine), resulting in progressive neurological recovery. Motor functions improved by postoperative day 6, and bladder function normalized by day 8, with full recovery observed by day 15. Steroid dose was gradually tapered (no specific information given) after 2 weeks, and a repeat MRI at this time demonstrated significant resolution of arachnoiditis and granulomas.

Study Author Conclusions

In conclusion, this case highlights that like any undetected pre-existing spinal pathology, asymptomatic tubercular arachnoiditis can contribute to cauda equina syndrome (CES) even after carefully administered spinal anesthesia. Therefore, after surgery under spinal anesthesia, careful monitoring for recovery of sensory and motor functions is important for early detection of a neurological complication such as CES.

In a case where CES is suspected: (1) the patient should be investigated thoroughly and an MRI done to identify and suitably address any underlying contributory spinal pathology, and (2) appropriate treatment should be immediately instituted.

 

References:

Sethi D, Gupta M, Sood S. Cauda equina syndrome after spinal anaesthesia in a patient with asymptomatic tubercular arachnoiditis. Indian J Anaesth. 2011;55(4):375-377. doi:10.4103/0019-5049.84864

 

Cauda equina syndrome following an uneventful spinal anesthesia in a patient undergoing drainage of the Bartholin abscess

Design

Case report

Case presentation

A 23-year-old female developed cauda equina syndrome (CES) following uneventful spinal anesthesia during surgical drainage of a Bartholin abscess. Spinal anesthesia was administered with a single puncture at the L3-L4 interspace using a 25-G Whitacre needle, through which a hyperbaric solution of 7.5 mg bupivacaine 0.75% and 15 mcg fentanyl was introduced. The perioperative course was devoid of complications, and the patient was discharged 12 hours postoperatively. However, by the following day, she reported bilateral lower extremity weakness, severe neuropathic pain, urinary retention, and sensory loss below T9. Neurological evaluation revealed flaccid paraparesis, left-sided monoparesis, and diminished osteotendinous reflexes. MRI demonstrated gadolinium enhancement at the cauda equina level, consistent with arachnoiditis and CES.

Initial interventions included oral pregabalin 75 mg q12h, tramadol 20 mg q8h, and IV dexamethasone 4 mg q6h. On postoperative day four, persistent severe deficits required escalation to high-dose IV methylprednisolone (1 g) therapy for five days, followed by oral prednisone. A multidisciplinary approach, including neurorehabilitation, was initiated, leading to gradual recovery.

By postoperative day nine, motor function slightly improved, and the patient ambulated with significant difficulty, necessitating ongoing oral prednisone (dose not provided). She was discharged on day 25 with sertraline, clonazepam, pregabalin, acetaminophen, prednisone, and physical rehabilitation. Full motor function and normal reflexes were regained over two months, with residual mild left thigh discomfort.

Study Author Conclusions

This describes a case of cauda equina syndrome after a single spinal administration of bupivacaine 0.75%. The explanation for this complication is uncertain, but could be due to a combination of needle or introducer trauma at the time of insertion or due to the neurotoxic properties of Bupivacaine. Early detection and treatment of complications after neuraxial anesthesia is essential to minimize the risk of permanent damage. 

 

References:

Merino-Urrutia W, Villagrán-Schmidt M, Ulloa-Vásquez P, et al. Cauda equina syndrome following an uneventful spinal anesthesia in a patient undergoing drainage of the Bartholin abscess: A case report. Medicine (Baltimore). 2018;97(19):e0693. doi:10.1097/MD.0000000000010693

 

Steroid-responsive cauda equina syndrome associated with GVHD after allogeneic hematopoietic stem cell transplantation

Design

Case report

Case presentation

A 43-year-old male presented with probable central nervous system graft-versus-host disease (CNS GVHD) manifesting as cauda equina syndrome five months after allogeneic hematopoietic stem cell transplantation. The patient, initially treated for acute myeloid leukemia (AML M1), underwent myeloablative conditioning with cyclophosphamide and total body irradiation, followed by GVHD prophylaxis with in vitro T-cell depletion (using CAMPATH-1H), T-cell add-back, and cyclosporine. The patient experienced hematological and meningeal relapse post-transplantation, which was managed with FLAG-IDA chemotherapy and intrathecal therapy, resulting in neurological and cytological resolution.

Six weeks after remission, the patient developed acute neurological deficits consistent with high cauda equina syndrome, including motor and sensory loss, saddle anesthesia, and sphincter dysfunction. Comprehensive evaluations excluded common post-transplant complications such as infectious, neoplastic, or drug-induced neurotoxicity based on cerebrospinal fluid (CSF) analysis, normal MRI, and absence of blasts.

The inflammatory CSF profile and concurrent skin GVHD, along with a rapid and significant response to high-dose IV (1 g/day for 5 days, starting 7 days after symptom onset) and intrathecal (two 40 mg injections, 5 days apart) methylprednisolone, strongly supported a presumptive diagnosis of CNS GVHD.

Study Author Conclusions

No consensus exists on the work-up and treatment options of this entity, and continued reporting of similar cases will help to determine the clinical significance of possible CNS GVHD and possible treatment options. Interestingly, while all cases previously described involved brain structures, this case presented as an isolated, albeit dramatic, cauda equina syndrome with no clinical or neuroradiological evidence for cerebral abnormalities.

Based on the exclusion of other diseases, the inflammatory state, clinical evaluation, laboratory results, and response to immunosuppressive treatment, the authors attribute this cauda equina syndrome to probable GVHD. This case is significant because it is the first description of cauda equina syndrome due to probable GVHD and the first where a trial of intrathecal steroid therapy was successful.

 

References:

Terrettaz M, Verholen F, Passweg J, Knipp S, Burkhard PR, Chalandon Y. Steroid-responsive cauda equina syndrome associated with GVHD after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41(3):315-316. doi:10.1038/sj.bmt.1705915