|Year : 2015 | Volume
| Issue : 4 | Page : 204-206
Antiphospholipid antibody syndrome presenting as transverse myelitis
Javvid M Dandroo MD 1, Naveed Mohsin1, Firdousa Nabi2
1 Department of Internal Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Prosthodonsia, Government Dental College, Srinagar, Jammu and Kashmir, India
|Date of Submission||10-Apr-2015|
|Date of Acceptance||29-Jun-2015|
|Date of Web Publication||26-Oct-2015|
Javvid M Dandroo
Department of Internal Medicine, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
The antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features, and a variety of other nonthrombotic neurological syndromes. Although the mechanism of neurological involvement in patients with APS is thought to be thrombotic in origin and endothelial dysfunction associated with antiphospholipid antibodies. APS presenting as acute transverse myelitis is very rarely seen with a prevalence rate of 1%. We are describing a foreigner female presenting as acute transverse myelitis which on evaluation proved to be APS induced. So far, very few cases have been reported in literature with APS as etiology.
Keywords: antinuclear antibody, antiphospholipid antibody, antiphospholipid antibody syndrome, acute transverse myelitis, cytomegalovirus, herpes simplex virus, low molecular weight heparin
|How to cite this article:|
Dandroo JM, Mohsin N, Nabi F. Antiphospholipid antibody syndrome presenting as transverse myelitis. Egypt Rheumatol Rehabil 2015;42:204-6
|How to cite this URL:|
Dandroo JM, Mohsin N, Nabi F. Antiphospholipid antibody syndrome presenting as transverse myelitis. Egypt Rheumatol Rehabil [serial online] 2015 [cited 2020 Jun 2];42:204-6. Available from: http://www.err.eg.net/text.asp?2015/42/4/204/168209
| Introduction|| |
Transverse myelitis is characterized by acute inflammation affecting a local area of the white matter of the spinal cord usually involving thoracic cord  . Patients age at the time of disease onset vary widely, ranging from childhood through the 80s  . The clinical presentation is characterized by the development of motor neurologic dysfunction, which is associated with sensory abnormalities (sensory level) and abnormalities of the autonomic nerves (sphincter disturbances).
Etiologically, acute transverse myelitis (ATM) has diverse causes. The five groups of disorders that present as acute myelopathy are demyelination, infections, other inflammatory disorders, vascular, and neoplastic and paraneoplastic. The first three are considered inflammatory disorders. Among these, demyelinating disorders are the most common. Demyelinating disorders include multiple sclerosis, neuromyelitis optica, acute demyelinating encephalomyelitis, and idiopathic myelitis. Infections include viral, bacterial, fungal, and parasitic. Common infectious causes are herpes simplex virus (HSV), herpes zoster virus, cytomegalovirus (CMV), and Epstein-Barr virus  .
Connective tissue disorders and granulomatous disorders presenting as acute or subacute myelitis are systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, mixed connective tissue disorder, Behcet's disease, and sarcoidosis ,, . Paraneoplastic disorders also cause acute/subacute myelitis  .
Involvement of the neuropsychiatric system in antiphospholipid syndrome (APS) causes high morbidity and mortality, with stroke and transient ischemic attack as the most common manifestations  . ATM is mainly associated with SLE and Sjogren's syndrome  . It is a rare neurologic complication of APS with a prevalence estimated at less than 1% of APS patients , . We are describing a very rare case of APS presenting as ATM.
| Case report|| |
A 56-year-old female foreigner from Italy was on tour to Kashmir when she started with progressive asymmetric weakness of both lower limbs with loss of sensations, more on the right lower limb than the left. This weakness was progressive over a period of 1 week with subsequent inability to get up and walk. This was associated with incontinence of urine. She denies recent infections, vaccinations or recent trauma. She never had an event like this before and considers herself to be 'very healthy'. There was significant past history of her recurrent pregnancy loss around 23 years back. She was evaluated that time in her home town, which proved to be due to APS, with positive antinuclear antibody and antiphospholipid antibody (APLA). Finally patient conceived and was on aspirin and low molecular weight heparin during pregnancy. At present she has two children 20 and 18 years old. On examination, her vitals, higher mental functions, and bulk were normal. Her lower limbs were hypotonic, power of grade I in right lower limb and grade II in left lower limb, with brisk reflexes and extensor planter response. Sensations were absent in both lower limbs with a level on trunk at T4-T5. Rest of clinical and systemic examination was normal. An impression of transverse myelitis was made in this patient.
On evaluation her hemogram, liver function test, kidney function test, electrolytes and blood gases, chest radiography, and ultrasonography of abdomen were found normal. Her coagulogram was deranged with activated partial thromboplastin time of 44 s (control 24 s), antinuclear antibody positive, and APLA positive. Viral serologies for HIV, Epstein-Barr virus, CMV, and hepatitis A, B, C, E, and HSV were negative. Computed tomographic brain was normal and MRI whole spine revealed a lower cervical and upper thoracic cord lesion that enhanced after gadolinium administration, a finding that is consistent with transverse myelitis ([Figure 1] and [Figure 2]).
|Figure 1 Contrast MRI of cervicothoracic region of cord showing contrast enhancement.|
Click here to view
|Figure 2 Contrast MRI coronal section at upper thoracic region showing contrast enhancement.|
Click here to view
Finally an impression of APLA induced transverse myelitis was made and patient was put on intravenous steroids and low molecular weight heparin combination. Power and sensations improved within a period of 1 week and she was able to walk. Patient was discharged on oral steroids.
| Discussion|| |
ATM has an estimated incidence of 1.34 to 4.6 per million , , but has been reported to be as high as 3.1 per 100 000 patient-years  . There does not seem to be a familial or ethnic predisposition for ATM and there is no evidence of geographic variation in its incidence  . As such, myelitis has been reported with increased incidence among women, but multiple sclerosis may partially explain this finding  .
Acute transverse myelitis can be presented as pyramidal (motor), sensory, and/or autonomic dysfunction to varying degrees. Symptoms typically develop over hours to days and worsen over days to weeks. Sensory symptoms usually present as paresthesia/hypoesthesia ascending from the feet with a demarcation at or near the level of the myelitis. Motor symptoms often include weakness that preferentially affects the flexors of the legs and the extensors of the arms (pyramidal distribution of weakness) and can include sphincter dysfunction  . Autonomic involvement is also common and can frequently cause bowel and bladder dysfunction, temperature dysregulation, or even bouts of hypertension which can be quite severe  .
When an acute myelopathy is suspected, a thorough neurological evaluation helps to determine the region of the spinal cord affected and then the next diagnostic step is to evaluate for a compressive or structural etiology. MRI with gadolinium contrast is the preferred imaging modality.
Once myelitis has been detected through MRI studies of the cord and cerebrospinal fluid evaluation showing signs of inflammation, the underlying etiology of the myelitis must be considered. While the most commonly identified cause of myelitis is demyelinating disease, infection in one study caused up to 12% of myelitis cases  , and must be the first diagnosis considered as it is important to identify treatable infections in the acute setting such as syphilis, herpes viruses, HIV, and tuberculosis  . Infectious or para infectious myelitis can be viral, bacterial, fungal, and/or even parasitic in etiology. The most common viral causes of myelitis are varicella zoster, enteroviruses, HSV-2, and CMV  .
APS is one of the rare etiologies of ATM. The APS is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant  . Harris et al.  described the case of a 45-year-old woman who developed transverse myelitis in the context of a lupus‐like illness. Although the mechanism of neurological involvement in patients with APS is thought to be thrombotic in origin. There is evidence that APLA may interfere with endothelial cell function and promote the procoagulant activity of endothelial cells  . Diagnosis is usually confirmed with contrast MRI and positive antibody test.
In light of the severe clinical presentation of ATM and its high rates of morbidity and mortality, early diagnosis and aggressive treatment are vital for therapeutic success. Sherer et al.  reported four cases of transverse myelitis associated with APLAs, and they suggest that early aggressive treatment (usually with pulses of methylprednisolone and cyclophosphamide) might improve the prognosis of these patients. Similarly, Chan and Boey  reviewed nine SLE patients with transverse myelitis who were treated with pulses of methylprednisolone and/or cyclophosphamide, and whose functional outcomes were considered good. Longitudinal case series of acute transverse myelitis reveal that approximately one-third of the patients recover with little to no disability; one-third are left with a moderate degree of permanent disability, and one-third have severe disabilities ,, .
Our patient was aggressively treated with high-dose steroids and her recovery was fast within a period of 1 week.
| Conclusion|| |
In light of the severe clinical presentation of ATM with APS and its morbidity and mortality, early diagnosis and aggressive treatment are vital for therapeutic success.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sherer Y, Hassin S, Shoenfeld Y, Levy Y, Livneh A, Ohry A, Langevitz P. Transverse myelitis in patients with antiphospholipid antibodies - the importance of early diagnosis and treatment. Clin Rheumatol 2002; 21
Carter D, Olchovsky D, Yonath H, Langevitz P, Ezra D. Simultaneous deep vein thrombosis and transverse myelitis with negative serology as a first sign of antiphospholipid syndrome: a case report and review of the literature. Clin Rheumatol 2006; 25
Kincaid O, Lipton HL. Viral myelitis: an update. Curr Neurol Neurosci Rep 2006; 6
Calgüneri M, Onat AM, Ozturk MA, Ozçakar L, Ureten K, Akdogan A, et al.
Transverse myelitis in a patient with Behcet′s disease: favorable outcome with a combination of interferon-alpha. Clin Rheumatol 2005; 24:64-66.
Moskau S, Urbach H, Hartmann A, Schmidt S. Multifocal myelitis in Behçet′s disease. Neurology 2003; 60:517.
Theodoridou A, Settas L. Demyelination in rheumatic diseases. J Neurol Neurosurg Psychiatry 2006; 77
Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004; 56
Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346
Tristano AG. Autoimmune diseases associated with transverse myelitis. Review. Invest Clin 2009; 50
Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al.
Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum 2002; 46
Kim JH, Lee SI, Park SI, Yoo WH. Recurrent transverse myelitis in primary antiphospholipid syndrome - case report and literature review. Rheumatol Int 2004; 24
Berman M, Feldman S, Alter M, Zilber N, Kahana E. Acute transverse myelitis: incidence and etiologic considerations. Neurology 1981; 31
Jeffery DR, Mandler RN, Davis LE. Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events. Arch Neurol 1993; 50
Klein NP, Ray P, Carpenter D, Hansen J, Lewis E, Fireman B, et al.
Rates of autoimmune diseases in Kaiser Permanente for use in vaccine adverse event safety studies. Vaccine 2010; 28
Bhat A, Naguwa S, Cheema G, Gershwin ME. The epidemiology of transverse myelitis. Autoimmun Rev 2010; 9
Sá MJ. Acute transverse myelitis: a practical reappraisal. Autoimmun Rev 2009; 9
Debette S, de Sèze J, Pruvo JP, Zephir H, Pasquier F, Leys D, Vermersch P. Long-term outcome of acute and subacute myelopathies. J Neurol 2009; 256
Schmalstieg WF, Weinshenker BG. Approach to acute or subacute myelopathy. Neurology 2010; 75(Suppl 1)
Jacob A, Weinshenker BG. An approach to the diagnosis of acute transverse myelitis. Semin Neurol 2008; 28
Levine SR, Deegan MJ, Futrell N, Welch KM. Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology 1990; 40
Harris EN, Gharavi AE, Mackworth-Young CG, Patel BM, Derue G, Hughes GR. Lupoid sclerosis: a possible pathogenetic role for antiphospholipid antibodies. Ann Rheum Dis 1985; 44
Oosting JD, Derksen RH, Blokzijl L, Sixma JJ, de Groot PG. Antiphospholipid antibody positive sera enhance endothelial cell procoagulant activity - studies in a thrombosis model. Thromb Haemost 1992; 68
Chan KF, Boey ML. Transverse myelopathy in SLE: clinical features and functional outcomes. Lupus 1996; 5
Altrocchi PH. Acute transverse myelopathy. Arch Neurol 1963; 9
Misra UK, Kalita J, Kumar S. A clinical MRI and neurophysiological study of acute transverse myelitis. J Neurol Sci 1996; 138
[Figure 1], [Figure 2]