Incomplete Brown-Séquard syndrome secondary to acenocoumarol-induced hematomyelia: A case report

Abstract

BACKGROUND

Intramedullary spinal cord hemorrhage, also known as hematomyelia, is an uncommon but clinically significant condition. It accounts for approximately 0.82% of all spinal hematomas, making it one of the least frequently encountered etiologies of acute myelopathy. Hematomyelia may result from a variety of causes, including vascular malformations (such as cavernomas or arteriovenous fistulas), bleeding diatheses, spinal cord tumors, trauma, or complications related to anticoagulation therapy.

CASE SUMMARY

Here, we describe a patient on acenocoumarol who developed incomplete Brown-Séquard syndrome secondary to spontaneous intramedullary hemorrhage. She presented to the emergency department with a one-week history of progressively worsening headache, neck pain, and left hemithoracic pain. Prompt magnetic resonance imaging allowed diagnosis, and conservative management led to neurological stabilization. Our case underscores the need for timely diagnostic imaging in patients taking anticoagulants who present with new neurological deficits. It also highlights the diagnostic challenges and therapeutic decisions associated with this rare complication.

CONCLUSION

In some cases, the cause of hematomyelia remains idiopathic. Vitamin K antagonists are widely used for the long-term prevention of thromboembolic events; hence, prompt diagnosis of potential complications is important.

Key Words: Hematomyelia; Intramedullary spinal hemorrhage; Brown–Séquard syndrome; Acenocoumarol; Anticoagulation complications; Case report

Core Tip: Spontaneous intramedullary spinal cord hemorrhage is a rare but devastating complication of vitamin K antagonist therapy. This case demonstrates that even therapeutic international normalized ratio levels do not guarantee hemorrhagic safety. A 70-year-old woman on acenocoumarol developed an incomplete Brown-Séquard syndrome due to thoracic hematomyelia. Prompt magnetic resonance imaging allowed diagnosis, and conservative management led to neurological stabilization. Clinicians should maintain high suspicion for spinal hemorrhage in anticoagulated patients with acute myelopathy.

INTRODUCTION

Intramedullary spinal cord hemorrhage, also termed hematomyelia, is an exceptionally rare neurological emergency and accounts for approximately 0.84% of all intraspinal hemorrhages[1-3]. It is characterized by bleeding within the spinal cord parenchyma and is associated with a high risk of permanent neurological disability or death if diagnosis and treatment are delayed[1,2]. Unlike epidural or subdural spinal hematomas, which often present with compressive symptoms, hematomyelia results in a complex clinical syndrome through direct destruction of neuronal tissue and secondary ischemia from cord edema[1,2,4].

The etiological spectrum of hematomyelia is heterogeneous and includes spinal vascular malformations (arteriovenous malformations and cavernomas), spinal cord tumors, trauma, inflammatory myelopathies, systemic coagulopathies, and iatrogenic anticoagulation[1-3]. In a significant proportion of cases, particularly in elderly patients, spontaneous hemorrhage occurs in the absence of a clearly identifiable structural lesion[1,2].

Vitamin K antagonists (VKAs), such as warfarin and acenocoumarol, remain widely used for stroke prevention in patients with atrial fibrillation, mechanical heart valves, and venous thromboembolism. Despite the increased use of direct oral anticoagulants, VKAs are still frequently prescribed in many regions[5,6]. Their clinical utility is limited by a narrow therapeutic window and unpredictable pharmacokinetics, resulting in a well-documented risk of spontaneous hemorrhage[6-8]. Intracranial bleeding is the most feared complication; however, spinal cord hemorrhage represents an underrecognized but devastating adverse effect[6,7].

Importantly, increasing evidence suggests that anticoagulant-related hemorrhage may occur even when the international normalized ratio (INR) is within therapeutic limits[6,7]. Advanced age, hypertension, diabetes mellitus, heart failure, and microangiopathic vascular changes are recognized as major predisposing factors that increase vascular fragility and bleeding risk[9-11].

Brown-Séquard syndrome (BSS), which is classically defined as ipsilateral motor weakness and proprioceptive loss with contralateral pain and temperature loss below the level of the lesion, most commonly results from traumatic hemisection of the spinal cord[12,13]. Nontraumatic causes, such as tumors, ischemia, infection, and hemorrhage, are particularly rare[2,12]. BSS secondary to intramedullary hemorrhage represents an exceptional clinical presentation and poses a diagnostic challenge, especially in the absence of trauma[2,12].

We report a rare case of spontaneous thoracic hematomyelia associated with therapeutic-dose acenocoumarol, which presented as incomplete BSS. This case underscores the persistent hemorrhagic risk of VKAs even within target INR ranges and highlights the importance of early magnetic resonance imaging (MRI) and multidisciplinary decision-making in patients taking anticoagulants and presenting with acute or progressive myelopathy.

CASE PRESENTATION

Chief complaints

A 70-year-old woman presented to the Emergency Department with a one-week history of progressively worsening headache, neck pain, and left hemithoracic pain.

History of present illness

The pain was described as deep, persistent, and radiating from the cervical region toward the upper thoracic spine. Symptom progression occurred in a stepwise manner over 4 days. On day 1, the patient developed persistent occipital headache and cervical pain. By day 2, the pain extended to the left hemithoracic region, and she noted abnormal right-sided truncal sensations; by day 3, progressive stiffness of the left lower limb developed, followed by urinary retention and constipation within the next 24 hours, prompting an emergency evaluation.

History of past illness

The patient had long-standing arterial hypertension for more than 15 years and was treated with angiotensin-converting enzyme inhibitors and diuretics, with home blood pressure values generally ranging from 130-145/75-85 mmHg. Type 2 diabetes mellitus was diagnosed 12 years earlier and was managed with insulin therapy, with recent HbA1c values between 7.2% and 7.8%.

She also had chronic heart failure and nonvalvular atrial fibrillation and was treated with acenocoumarol for approximately 7 years. Anticoagulation was monitored regularly with INR testing every 3-4 weeks. Over the preceding six months, the INR values remained stable within the therapeutic range (2.0-3.0), without documented supratherapeutic excursions or recent dose adjustments. The last INR measurement prior to symptom onset (10 days earlier) was 2.4.

Personal and family history

No family history of spinal disorders or bleeding diathesis was reported.

Physical examination

On neurological examination, the patient was alert and oriented. Sensory testing revealed right-sided dysesthesia with a well-defined T4-T5 sensory level and ipsilateral impairment of pain and temperature sensation. In contrast, pyramidal signs were present in the left lower limb, with hyperreflexia and increased tone but without severe motor weakness. Gait was preserved. Sphincter dysfunction was present, with urinary retention and constipation. These findings were consistent with those of incomplete BSS.

Laboratory examinations

Coagulation tests revealed a prothrombin time of 30% and an INR of 2.6. Thyroid, infectious, tumor marker, autoimmune, and serum protein electrophoresis panels were within normal limits. No evidence of systemic infection, malignancy, or inflammatory disease was detected (Table 1).

Table 1 Laboratory findings.

Laboratory panel	Result
Coagulation panel
PT (%)	30
INR	2.6
Thyroid panel
TSH (mU/L)	0.418
FT3 (pg/mL)	1.83
FT4 (ng/dL)	1.3
Anti-TPO (IU/mL)	3
Infectious panel
HIV 1/2	Negative
HBsAg	0.32 S/CO (negative)
Anti-HCV	0.66 S/CO (negative)
Protein electrophoresis
Albumin (%)	56.5
α1-globulins (%)	3.6
α2-globulins (%)	14.4
β1-globulins (%)	6.5
β2-globulins (%)	7.7
γ-globulins (%)	11.3
A/G ratio	1.3
Autoimmune panel
ANA	< 1:160
Anti-dsDNA (IU/mL)	8.6
MPO (RU/mL)	1.5
RF (IU/mL)	< 20
Tumor markers
CEA (ng/mL)	2
AFP (ng/mL)	4
CA-125 (U/mL)	11.8
CA-19-9 (U/mL)	< 2.06
CA-15-3 (U/mL)	13

PT: Prothrombin time; INR: International normalized ratio; FT3: Free triiodothyronine; FT4: Thyroxine; TPO: Thyroid peroxidase; HIV: Human immunodeficiency virus; HCV: Hepatitis C virus; ANA: Antinuclear antibody; MPO: Myeloperoxidase; RF: Rheumatoid factor; CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; CA: Cancer antigen.

Given the absence of systemic inflammatory signs and normal autoimmune screening, additional vasculitis markers (including ANCA), coagulation factor VIII, and IX activity assays were not performed, as clinical suspicion for primary vasculitis or congenital coagulopathy was low. The platelet count and fibrinogen level were normal, and there was no personal or family history suggestive of inherited bleeding disorders (Table 1).

Imaging examinations

Urgent whole-body computed tomography revealed only chronic degenerative spondyloarthrosis. On the second day of hospitalization, owing to neurological deterioration with new left lower limb weakness and nuchal rigidity, a spinal MRI was performed. MRI revealed an eccentric intramedullary lesion at the T2-T3 level with mixed T2 signal intensity consistent with acute intramedullary hemorrhage, surrounded by extensive medullary edema and thin peridural hemorrhage.

The discrepancy between the MRI-defined lesion level and the clinical sensory level (T4-T5) was attributed to longitudinal edema spread, tract involvement, and individual dermatomal variability, which is a well-recognized phenomenon in intramedullary lesions. Abnormal serpiginous vascular structures were initially suspected (Figure 1). Digital subtraction angiography (DSA) of the spinal vasculature revealed no evidence of arteriovenous malformation or fistula (Figure 2).

Figure 1 Magnetic resonance imaging of the thoracic spine showing an intra-medullary lesion at the Th1-Th2 level with mixed intensity on T2-weighted. A and B: Axial sections; C and D: Sagittal sections.

Figure 2 Patient angiography. A and B: Spine digital subtraction angiography did not reveal any vascular lesion; C: Adamkiewicz artery.

MULTIDISCIPLINARY EXPERT CONSULTATION

Following a multidisciplinary discussion involving neurology, neurosurgery, radiology, and cardiology, anticoagulation was immediately discontinued. Given the stable neurological status, absence of significant mass effects, and high surgical risk, conservative treatment was recommended.

FINAL DIAGNOSIS

Acenocoumarol-associated spontaneous intramedullary spinal cord hemorrhage (hematomyelia) at the T2-T3 level presenting with incomplete BSS.

TREATMENT

Therapeutic anticoagulation was discontinued. Despite evidence of hemorrhage, a specific reversal with vitamin K or prothrombin complex concentrate was not administered, as the INR was considered within the therapeutic range, neurological deficits were non-progressive, and imaging showed no hematoma expansion or severe cord compression. Because of the patient’s high thromboembolic risk secondary to atrial fibrillation, prophylactic enoxaparin (4000 IU once daily) was prescribed for 21 days. Close neurological monitoring and serial MRI follow-up were planned. No surgical intervention was required because of neurological stabilization.

OUTCOME AND FOLLOW-UP

During hospitalization, the patient’s pain gradually improved, and motor and sensory findings stabilized. Neurological status was assessed using serial neurological examinations and the American Spinal Injury Association (ASIA) Impairment Scale, which was performed at baseline, weekly during hospitalization, and at 1- and 3-month follow-ups. The patient remained ASIA grade D, with partial sensory improvement and stable motor function. Follow-up MRI showed no expansion of the hematoma. Transition to a non-vitamin K oral anticoagulant was considered after documented hematoma resolution on interval imaging.

DISCUSSION

Spontaneous intramedullary spinal cord hemorrhage is among the rare causes of acute myelopathy and remains a diagnostic challenge because of its variable clinical presentation and broad spectrum of potential etiologies[1,3,4]. The initial symptoms are often nonspecific and include localized neck or back pain, radicular pain, headache, and subtle sensory disturbances, frequently preceding the onset of overt neurological deficits by hours or days[1,4]. This prodromal phase may lead to misdiagnosis as degenerative spine disease, ischemic myelopathy, or inflammatory transverse myelitis, particularly in elderly patients with preexisting spinal pathology[1,2,4,14].

In our patient, the initial presentation of neck and hemithoracic pain followed by asymmetrical sensory disturbances and pyramidal signs was highly suggestive of a hemicord lesion. The presence of ipsilateral pyramidal signs with contralateral sensory impairment fulfilled the criteria for incomplete BSS. This classical neurological syndrome is most commonly associated with traumatic penetrating injuries, while nontraumatic etiologies remain distinctly uncommon[12,13]. Reported nontraumatic causes include cervical disc herniation, tumors, multiple sclerosis, spinal infarction, and, exceptionally, intramedullary hemorrhage[2,12,13].

Anticoagulation-related hematomyelia is rare but increasingly recognized due to the widespread use of anticoagulants among the elderly people[5-7,14]. Most reported cases involve warfarin; however, acenocoumarol shares the same mechanism of vitamin K-dependent clotting factor inhibition and has a comparable hemorrhagic risk[6,7]. The most striking aspect of our case was the occurrence of hematomyelia despite a therapeutic INR of 2.6, reinforcing the fact that INR values reflect systemic coagulation status but do not reliably predict bleeding risk at the microvascular level[6,7,10].

Several patient-specific factors likely contributed to the hemorrhagic event in our case. Advanced age, chronic hypertension, diabetes mellitus, and chronic heart failure are independently associated with endothelial dysfunction and small-vessel disease, which significantly weaken vascular integrity[10,11]. These microangiopathic changes render spinal cord vessels particularly vulnerable to rupture under anticoagulation therapy, even in the absence of structural vascular malformations[2,7,10].

MRI remains the gold standard for the diagnosis of hematomyelia[2,4,15]. Signal characteristics vary with the age of the hemorrhage, allowing accurate temporal staging[4,15]. In the acute phase, hemorrhage typically appears hyperintense on T1-weighted images and heterogeneous on T2-weighted sequences, with associated extensive cord edema[4,15]. In our patient, MRI not only confirmed the intramedullary nature of the lesion but also demonstrated associated peridural hemorrhage and significant surrounding edema, explaining the progressive neurological deficits. Because of the initial suspicion of abnormal vascular structures, DSA was performed appropriately and excluded arteriovenous malformation or fistula, thereby supporting the diagnosis of anticoagulant-induced spontaneous hemorrhage[7,14].

The optimal management of hematomyelia remains controversial because of the absence of randomized controlled trials and the rarity of this condition[1,3,16]. Treatment strategies are guided by the severity and progression of neurological deficits, the presence of mass effects, and the underlying etiology[3,16]. Surgical evacuation may be lifesaving in patients with rapid neurological deterioration, severe cord compression, or an expanding hematoma[1,16]. Conversely, conservative management is widely accepted for neurologically stable patients without significant mass effects[3,6,7,15,16] (Table 2).

Table 2 Prognostic factors and outcome predictors in intramedullary spinal cord hemorrhage.

Category	Favorable prognostic factors	Poor prognostic factors
Clinical presentation	Incomplete neurological deficit	Complete sensorimotor paralysis
	Preserved ambulation	Early loss of ambulation
	Slow or non-progressive symptoms	Rapid neurological deterioration
Timing	Early MRI diagnosis (< 24-48 hours)	Delayed diagnosis
Radiological features	Small, focal hemorrhage	Long-segment cord involvement
	Limited cord edema	Severe edema and mass effect
Etiology	Isolated anticoagulant-related bleed	Vascular malformation or tumor
Management	Prompt cessation/reversal of anticoagulation	Ongoing anticoagulation
	Neurological stability under conservative treatment	Recurrent bleeding
Patient factors	Younger age, fewer comorbidities	Advanced age, hypertension, diabetes, heart failure

MRI: Magnetic resonance imaging.

In our case, a multidisciplinary decision favored conservative treatment, given the patient’s stable neurological status, absence of significant cord compression, and high surgical risk related to cardiovascular comorbidities[3,5-7,11]. Immediate discontinuation of acenocoumarol was mandatory[5,6]. However, this created a therapeutic dilemma because of the patient’s high thromboembolic risk from atrial fibrillation. The use of low-dose enoxaparin for short-term thromboprophylaxis represents a compromise between hemorrhagic and ischemic risks[5]. The timing and choice of long-term anticoagulation after spinal cord hemorrhage remain unresolved issues, and decisions must be individualized, balancing the risks of recurrent bleeding against the potentially catastrophic consequences of cardioembolic stroke[5-7].

Assessment of neurological severity and prognosis of spinal cord hemorrhage is standardized using validated functional scales. The ASIA Impairment Scale is widely used to classify the degree of neurological deficit and has important prognostic implications. Patients presenting with incomplete injuries (ASIA grades C-D) generally experience more favorable functional outcomes than those with complete deficits (ASIA grade A). In the present case, the patient’s neurological status corresponded to ASIA grade D, reflecting preserved motor function below the neurological level. This classification supported the decision for conservative management and was consistent with the subsequent neurological stabilization observed during follow-up[17,18].

Neurological outcomes after hematomyelia are highly variable and largely dependent on the extent of initial cord damage and the rapidity of diagnosis[1,4,16]. Early MRI and prompt correction of coagulopathy are the most critical determinants of functional recovery[3,5]. Our patient experienced neurological stabilization and partial improvement, supporting previous observations that early recognition and conservative management can be effective in selected cases[6,7,15].

This case contributes to the limited body of literature on anticoagulant-related hematomyelia presenting as BSS and emphasizes several key clinical messages: First, therapeutic INR levels do not preclude severe spinal hemorrhage[5-7,10]; second, acute or progressive hemicord syndromes in patients taking anticoagulants should prompt immediate spinal MRI[3,4,15]; and third, management must be individualized through multidisciplinary collaboration[3,5,14,16,17].

CONCLUSION

Spontaneous intramedullary spinal cord hemorrhage should be considered in any patient taking anticoagulants who presents with acute or progressive myelopathy, even when the INR remains within the therapeutic range. Early MRI diagnosis and multidisciplinary management are essential for preventing irreversible neurological damage.