COVID-19-Related Spinal Subdural Hematoma Presented with Acute Compressive Myelopathy with a Review of the Literature

A novel case of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) also known as coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019 and rapidly spread throughout the world as a pandemic [1]. Since COVID-19 causes mild to severe acute respiratory syndrome [2], most studies in this field have only focused on different aspects of pathogenesis in the respiratory system. However, evidence suggests that COVID-19 may also affect the central nervous system [3].

In a recent COVID-19 study in China, concerns have been raised that this virus may be neuroinvasive. Neurologic manifestations in up to 84% of hospitalized patients have been described in series from China [4]. Neurological symptoms were reported in 37% (50% in severe infection) of 214 COVID-19 patients reported from Wuhan, including nonspecific symptoms of headache and dizziness (20% of cases), altered mentation (15% of severe infection), severe muscle ache and myalgia (20% of cases), and loss of taste and smell sense, which may be an initial indicator of COVID-19 infection [4]. Several reports indicated increasing evidence that the nervous system is frequently involved in patients with COVID-19, and symptoms related to olfactory dysfunction have been interpreted as evidence of central nervous system involvement and showed olfactory neuropathy within 3 weeks from the onset of illness [4‒6].

COVID-19 can cause multi-organ dysfunction within 4–5 days and about 97.5% of patients will develop symptoms within 11 days. This virus uses the spike protein to attach to the host angiotensin-converting enzyme 2 (ACE-2) receptor and enters the target cells. These receptors are expressed in various tissues such as the respiratory epithelial cells, glial cells, neurons, lung, kidney, intestine, brain, and vascular endothelium [6‒9]. The immune system can identify the virus and may have a dual function in the case of COVID-19 infection. Recently, a report indicated that in 85% of patients, a proportionate immune response removes the virus and the patients remained asymptomatic or developed only mild symptoms, while in 10–15% of patients, the immune response was intense and disproportionate. The immunopathological phase follows the viral invasion, and the patient develops an aggressive type of disease, cytokines, and type I interferons (IFN-I) secreted by the immune and epithelial cells play a major role in antiviral immunity, while the weak response of IFN-I has been described in aggressive forms of COVID-19 infection [10]. Additionally, it was reported that COVID-19 variants and anti-IFN-I autoantibodies reduced the IFN-1 response [11].

Aggressive inflammation in response to infection leads to severe forms of the disease. This aggressive inflammation is described as a “cytokine storm” [12] Pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β are released by the innate immune system, mainly by myeloid cells such as monocytes, polymorphonuclear neutrophils, and macrophages after recognition of the virus [13]. IL-6 is a cytokine synthesized by immune cells and other types of cells, such as endothelial cells. It activates the cells of the adaptive immune system, such as Th17 lymphocytes and follicular Th cells, and the innate immune cells, including monocytes and polymorphonuclear neutrophils. IL-6 is useful for the immune response; furthermore, it may be injurious if secreted in excessive amounts, leading to inflammation and tissue damage [14]. Failure of the immune system to eliminate the virus at the epithelial barrier leads to the progression of the viral invasion toward the endothelium. The endothelial cells contain ACE-2 receptors for the S protein of COVID-19 [15]. The resulting endothelial inflammation is associated with thrombotic phenomena in the context of COVID-19 infection, including microthromboses [16] macrovascular thromboses, and pulmonary embolism [17].

The complement system plays an important role in the immune response against COVID-19 in association with both hypercoagulability and endothelial cell injury. All proteolytic cascades, kallikrein, coagulation, and complement systems work simultaneously to promote the thrombo-inflammatory process. Additionally, these three systems can cleave and activate the complement C3 peptide, and this cleavage is amplified by the COVID-19 spike protein, which, upon binding to cell surface glycosaminoglycans, causes the activation of the complement alternative pathway. Coagulation cascade, plasma kallikrein, and complement system may promote endothelial cell dysfunction that may constitute the core pathophysiology of COVID-19. As a result, using the inhibitors of the complement cascade and receptors for C3 and C5 may have the potential to be included in COVID-19 therapy [18].

The presence of COVID-19 infection may increase the risk of thrombotic events due to a hypercoagulability state and inflammation, resulting in arterial and venous thrombosis and ischemic strokes [18‒21]. Studies reported a high incidence of venous thromboembolic events in hospitalized patients with COVID-19, in spite of thromboprophylaxis [22, 23]. Furthermore, it was reported that in COVID-19 patients, the risk of hospital-associated venous thromboembolism extends from the admission time and over the first 3 months post-hospital discharge [23‒27]. The varied symptoms of COVID-19 are dependent on the patient’s age and underlying medical illnesses, as well as the condition of the individual’s immune system [28].

Spinal subdural hematoma (SSDH) is a rare condition and may lead to significant neurologic manifestations. In some cases, there is no identified risk factor, so it is named “idiopathic” SSDH [29], and this is considered very rare. Usually, the risk factors for SSDH include anticoagulant drugs, coagulopathy, vascular malformations, infection of the spine, trauma, and iatrogenic causes [30]. The exact mechanism is unclear; however, one theory has suggested that unlike the intracranial subdural space or the spinal epidural space, there are no bridging veins or major blood vessels in the spinal subdural space. Nevertheless, this theory proposes that when intrathoracic pressure is elevated significantly, hemorrhage occurs in the more vascular subarachnoid space and infiltrates through the arachnoid mater into the subdural space where blood accumulation occurs [31].

Some studies have proposed the bleeding in SSDH results from the rupture of vessels within the subarachnoid space after a rapid rise in intra-abdominal or intrathoracic pressure [32]. Most of the SSDH presented in the range of 45–60-years-old patients and were mostly located in the thoracic region [33].

In this report, we present a COVID-19-related SSDH case with acute compressive myelopathy. We have not found any such case reported in studies of COVID-19 infection.

A 55-year-old, Iraqi male presented to the Middle Euphrates Neurosciences Center in Al-Najaf City in Iraq with sudden onset of bilateral lower limb weakness, and urinary retention with severe lower back pain for 2 h before admission. He had a history of hypertension and diabetes mellitus, on antihypertensive (amlodipine 5 mg/day oral tablets) and oral hypoglycemic (glimepiride 2 mg/day oral tablets) medications. He had a 1-week history of low-grade fever following contact with a COVID-19 patient in his family. He had no history of trauma, bleeding diathesis, coagulopathy, vasculopathy, or vascular malformations, and was not on anticoagulation drugs. The vital signs upon admission were as follows: blood pressure 150/90 mm Hg with no documented hypertension spikes, heart rate 90 beats/min and regular, body temperature 37.8°C, respiratory rate 18 breaths/min, and SPO₂ was 97% on room oxygen. The neurological examination was as follows: awake, oriented, GCS 15, normal cranial nerves, and no meningeal signs. The patient’s upper limbs had normal tone, power, reflexes, and sensation. He has flaccid areflexic paralysis of the lower limbs (power grade 0/5), with a total loss of all sensory modalities below the 12th spinal thoracic segment (T12) and a bilateral absence of the Babinski sign. All cardiac, abdominal, and locomotor system examinations were normal with mild crackles at the lung bases.

After admission, he underwent blood tests, chest CT, and spinal MRI. His bladder was evacuated by a Foley catheter. The results of the blood test demonstrated classical blood film findings (mainly lymphopenia) in COVID-19 patients, as shown in Table 1, with high readings of serum ferritin, C-reactive protein, and D-dimer. Prothrombin time, aPTT, and INR values were within the normal range. The patient has no past history or clinical features of vasculopathy, and no further investigation was done.

A chest CT scan of the patient showed multiple bilateral peripheral ground-glass opacities of the lungs as shown in Fig. 1, which is highly suggestive of COVID-19 infection. An MRI scan for the dorsal and lumbosacral spine with pre-and post-contrast showed a long extra-dural lesion at levels D12, D11, D10, and D9 (hyperintense on T1 and T2) with homogenous post-contrast enhancement. It was diagnosed as SSDH. The lesion caused significant pressure on the spinal cord as illustrated in Fig. 2. A real-time reverse-transcription-polymerase chain reaction test using a nasopharyngeal swab was positive for COVID-19.

The initial finding in intensive care was SSDH. Other possible conditions were suspected such as acute vascular myelopathy, acute compressive myelopathy, and acute inflammatory myelopathy. The presence of urinary retention, sensory level, and sudden onset all raised high clinical suspicion of acute vascular myelopathy. However, the loss of all modality of sensation with the presence of severe back pain makes ischemic myelopathy unlikely favors the compressive cause. When we think about the inflammatory cause, it is unlikely to be sudden onset, so the spinal MRI is mandatory and needed to be done urgently to confirm or exclude the possibility of compressive lesion which if present may necessitate urgent surgery. The diagnosis of SSDH was based on the clinical findings mentioned above and radiological findings in spinal MRI.

Immediately after admission, the following was administered: steroids in the form of methylprednisolone (1 g) intravenous infusion, proton pump inhibitor (esomeprazole 40 mg IV infusion), and fluid therapy (0.9% normal saline) with pain killer drugs in the form of paracetamol injection (1 g). On the 2nd day after admission, the patient was transferred to the operation room. Hematoma evacuation was performed by the neurosurgeon with the restoration of spinal cord pulsation.

On follow-up, 3 weeks later, the sensation and power of the lower limbs improved (power grade 3). Two months post-operation, the patient was able to walk with a crutch, and the spinal MRI was done as shown in Fig. 3.

To the best of our knowledge, this is the first case report demonstrating an association between SSDH and COVID-19. This warrants great concern because it results in spinal cord compression with severe neurological deficits. As reported in the literature, there is a wide range of neurological symptoms in COVID-19 cases, extending from specific symptoms (loss of smell or taste, myopathy, total paralysis, and stroke) [34] to more nonspecific symptoms (headache, decreased level of consciousness, vertigo, or seizure) [35]. Cerebrovascular accidents are reported more in diabetic and hypertensive patients [36]. Other reported neurological complications include encephalitis, viral meningitis, post-infectious brainstem encephalitis, myositis, post-infection acute disseminated encephalomyelitis, Gillian Barre syndrome, and cerebrovascular accident [37]. One of the rare cases of acute necrotizing encephalitis was also reported in a 59-year-old patient with COVID-19 who presented with fever, dry cough, and a change in mentality [38]. Recently, the association between COVID-19 and coagulopathy has gained increased interest, especially for severe cases, and its association with the fulminant activation of coagulation and consumption of coagulation factors [39, 40].

The symptoms caused by SSDH vary greatly from back pain alone to complete paralysis [41]. A high degree of clinical suspicion is very important for early diagnosis, especially in patients with unknown causes for sudden severe back pain and neurologic deficit. In our case presentation; the diagnosis of SSDH was based on the clinical findings and radiological findings such as MRI [42] as shown in Fig. 2. Surgery was arranged quickly within 12 h of admission and the hematoma was evacuated. Three weeks later postoperatively, the patient sensory level and power of the lower limbs improved reaching grade 3 with the help of physiotherapy.

The mechanism of action that leads to SSDH due to COVID-19 is not yet established. Since our patient suffers from hypertension, diabetes mellitus, and activation of coagulation pathway(s) as indicated by the high level of D-dimer, these conditions are usually associated with chronic endothelial dysfunction. Endothelial and nerve cells are known to express ACE-2 receptor, a potential target for COVID-19 infection. Our hypotheses regarding the hypercoagulability and hemorrhagic effects of COVID-19 are as follows. First, ACE-2 receptors play an important role in vascular autoregulation and vascular blood flow, and any dysfunction of these receptors by COVID-19 invasion may result in disruption of autoregulation that may lead to vascular wall rupture in the presence of hypertension spikes [43]. This virus can invade and damage blood vessels, by overexpression of the viral entry protein; ACE-2 within vascular endothelium may cause endotheliitis and diffuse endothelial damage [44, 45]. Second, a subset of COVID-19 infected patient develops a systemic hyperinflammatory syndrome with fulminant hypercytokinemia, and hypoxia of endothelial cells is other possible causes. This may result in vascular remodeling and loss of vascular wall integrity which leads to a higher risk of rupture and hemorrhage [38, 46‒48]. The limitations of this study are the undefined mechanism that leads to this hemorrhage and the risk of incidence of SSDH in patients infected with COVID-19 as compared to the general population, both of which are still unknown.

Spinal subdural hematoma should be suspected in any patient who presents with acute onset of severe back pain and myelopathy without a history of trauma. Coagulopathy associated with COVID-19 infection should increase the suspicion of SSDH which needs immediate surgical treatment to save the spinal cord and prevent a devastating neurological sequel. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000528310).

The authors thank the Middle Euphrates Neurosciences Center and the entire staff of the intensive care unit. The research and publication of the article were self-funded by the authors.

Written informed consent from the patient, including the approval to publish this case report and any accompanying images, was obtained. Additionally, there is no information revealing the patient’s identity. An approval letter from the Institutional Review Board at Kufa University on May 20, 2021 (Ref #: MEC-21-012) was obtained.

The authors have no conflict of interest to declare.

No funding was received for this study.

Hasanain A. Al-Khalidi performed the clinical evaluation and data collection and revised the final draft of the manuscript. Hayder K. Hassoun supervised and performed the clinical evaluation and data collection, drafted the initial version of the manuscript, and revised the final draft of the manuscript. Zahra Aljid performed the CT scan and MRI, interpreted the data, and revised the final draft of the manuscript. Zuhair Allebban performed laboratory testing, collected laboratory data, reviewed the literature, and revised the final draft of the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.