| Abstract|| |
We report here a case of severe lupus nephritis, Raynaud's phenomenon, digital gangrene and optic neuritis who, developed acute transverse myelitis (ATM). SLE can present virtually with any complication in the central nervous system (CNS) and ATM is a rare but serious manifestation. It is noteworthy that ATM developed in this patient while she was on intravenous cyclophosphamide (IVC) therapy having already finished six doses of monthly infusions of 10 mg/kg body weight. The patient responded well to methyl-prednisolone pulse therapy, IVC and plasmapheresis. She recovered fully and is doing well after nine months of follow-up.
Keywords: Systemic lupus erythematosus, Transverse myelitis, Pulse methylprednisolone, Cyclophosphamide.
|How to cite this article:|
Mitwalli AH, Memon NA, Abu-Aisha H, Al-Wakeel JS, Tarif N, Askar A, Hammad D. Transverse Myelitis in a Patient with Severe Lupus Nephritis: A Case Report. Saudi J Kidney Dis Transpl 2002;13:492-7
|How to cite this URL:|
Mitwalli AH, Memon NA, Abu-Aisha H, Al-Wakeel JS, Tarif N, Askar A, Hammad D. Transverse Myelitis in a Patient with Severe Lupus Nephritis: A Case Report. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2020 Oct 23];13:492-7. Available from: https://www.sjkdt.org/text.asp?2002/13/4/492/33104
| Introduction|| |
Amongst the diverse manifestations of systemic lupus erythematosus (SLE) transverse myelitis is a rare and serious complication, affecting the central nervous system (CNS). Optimal therapy of this condition is controversial and several studies have found that CNS manifestations indicate poor prognosis.  Other studies, however, have shown that the majority of the CNS complications resolve and were not associated with poor outcome. ,
We present here a patient with lupus nephritis who after eight months of diagnosis, presented with acute transverse myelitis (ATM) while on cytotoxic therapy. She was managed with intravenous methyl prednisolone pulse (IVMPP) and plasmapheresis besides cyclophosphamide. The pathophysiology and management of ATM with a review of literature is discussed.
| Case Report|| |
A 15-year-old Saudi female presented to a peripheral hospital with facial swelling, joints pain, and painful infracted fingertips. Physical examination showed an ill looking, thinly built girl with puffy face and pallor. She had small shotty non-tender lymph nodes in the cervical and axillary regions. Abdominal examination revealed hepatosplenomegaly and mild ascites while the respiratory, cardiac, and CNS examinations were normal. Investigations showed hemoglobin (Hb) 113 gm/L, white blood cell (WBC) of 8 x 10 3 /µl and platelet count of 138 x 10 3/µl. Mid stream urine (MSU) examination showed proteinuria of 3+, 40 red blood cells (RBC)/HPF, 15 WBC/HPF and granular casts. Blood urea was 51.4 mmol/L and serum creatinine, 575 µmol/L. Anti-nuclear antibody (ANA) titre was strongly positive (1:10240) with positive antidouble stranded nuclear antibody (antiDNA) and hypocomplementemia (C3 and C4). Diagnosis of SLE with severe renal involvement, digital vasculitis with impending gangrene was made. The patient was referred to the King Khalid University Hospital (KKUH) for further management.
At KKUH, the evaluation confirmed the above findings. Renal biopsy was not done initially in view of her severe illness and her refusal. Clinical diagnosis of probable class IV lupus nephritis was made and she was treated with IVMPP 1 gm daily for three days, followed by intravenous (i.v.) cyclophosphamide (10 mg/kg). Prostacycline was administered i.v. for Raynaud's phenomenon. Her renal functions improved markedly and came to normal values six weeks later. Serum creatinine dropped from 575 µmol/L to 47 µmol/L [Table - 1] and the digital gangrene showed marked improvement and ultimate healing. While in hospital, she developed fever and cough. Chest X-ray showed right lung infiltrates, which did not respond to bactericidal coverage. A computerized tomographic (CT) Scan of the chest showed cavitating lung lesion in the right middle lobe and anterior segment of the lower lobe. Sputum was negative for acid-fast bacilli on Zeil-Nelson staining. Later, candida growth was identified and fluconazole was started to which she responded and her fever and cough eventually subsided. The patient was discharged in good condition after five months of hospitalization. By that time, she had received five monthly boluses of i.v. cyclophosphamide (IVC), and she was in clinical remission. Renal function remained normal. ANA titres and anti-DNA titres were decreased but yet remained high, C3 level normalized but C4 remained low [Table - 1].
One month later, she was re-admitted with loss of vision in the right eye. Optic neuritis and optic atrophy was diagnosed, most probably secondary to SLE; it may be noted that the patient developed optic neuritis while being on IVC and maintenance prednisolone. Lupus anticoagulants were positive on this admission. Management included IVMPP for three days, maintenance oral prednisolone thereafter and heparin followed by warfarin. The international normalized ratios (INR) ranged between 1.5-2.5. Since the patient lived in a remote village and she did not seem to be very compliant in taking medications, we thought the above anti-coagulation was satisfactory. She was discharged after five weeks with improved vision and normal renal functions.
Two months later (i.e. eight months after the initial presentation), she presented with sudden onset of generalized fatigability, weakness in both lower limbs and inability to walk for three days. She was incontinent of urine and faeces. Neurological examination revealed reduced power (2/5) in both lower limbs, exaggerated ankle and knee jerks and extensor plantar response bilaterally. Sensory examination revealed sensory loss with level at D4. Repeat CT scan of brain showed brain atrophy and cerebritis. Magnetic resonance imaging (MRI) of the spinal cord did not reveal any mass effect or compression. A diagnosis of transverse myelitis was made.
At this stage antiphospholipid (APL) antibodies were looked for, and found to be positive. This time again methylprednisolone pulse therapy was repeated and additionally, five sessions of plasmapheresis were given and her scheduled seventh dose of cyclophosphamide (quarterly now) was given one month earlier. She responded slowly and was discharged three weeks later in good condition. She could walk without support and had good sphincter control. At the time of discharge, her blood urea was 3.6 mmol/L, serum creatinine 67 µmol/L, and serum complements were normal. However, ANA still remained high at 1:2560 and anti-DNA 1:42. Twenty-four hours urine protein excretion was 0.08 gm and creatinine clearance was 61 ml/minute. During this admission, renal biopsy was performed, eight months after her initial presentation, and showed WHO class III lupus nephritis. She was advised regular followup for cyclophosphamide pulse therapy and anti-coagulant monitoring. Nine months after her episode of ATM, she was doing well with no neurological deficit and had normal renal functions.
Neuropsychiatric manifestations are not uncommon in SLE and the observed incidence has varied from 13 to 59%. , West et al defined their patients with neuro-psychiatric lupus erythematosus (NPLE) into three groups; diffuse, focal or complex presentations.  The "diffuse" neurologic presentation group included organic brain syndromes, coma, grandmal seizures, intractable headaches and psychiatric disturbances (Global dysfunctions). "Focal presentation" was defined as symptoms that could be attributed to lesions in specific brain area and included hemiparesis, movement disorder, focal seizures, transverse myelitis and cranial nerve palsies. A complex presentation was defined as both diffuse and focal manifestations occurring concurrently in a patient. 
Diffuse presentation of NPLE is more common, and amongst the focal presentations ATM is well recognized although rare. 
The pathogenesis of NPLE is incompletely understood, but pathologic studies have provided useful information. A large number of autopsies have shown that small or medium size vasculitis of the brain arteries is uncommon. , What is more commonly seen is degenerative and proliferative abnormalities of the interna media of small vessels, occasionally with occlusion, perivascular infiltrates, microinfarcts and microhemorrhages. This type of vasculopathy is associated with microscopic as well as larger infarcts accounting for some of the neurologic manifestations of NPLE. ,, Likewise, embolic infarcts from either a cardiac source or intravascular thrombosis due to APL antibodies can account for some of the clinical manifestations observed.  However, many patients with NPLE, and in particular with diffuse manifestations demonstrate normal brain anatomy, suggesting different pathogenetic mechanisms, other than vascular occlusion.
Anti-neuronal antibodies, gaining entry to the CNS through the choroid plexus by disruption of the blood brain barrier from micro-infarcts or by enhanced vascular transport due to ischemia and serotonin released from platelet aggregation, are thought to be other mechanisms causing NPLE manifestations.
NPLE patients with diffuse manifestations, either alone or in combination with focal symptoms (complex NPLE), demonstrated anti-neuronal antibodies, elevated lgG index and oligoclonal bands in their CSF much more frequently than did SLE control patients.  Although still controversial, serum antiribosomal-P antibodies have been reported to be positive in 45% of SLE patients with severe psychosis and/or depression. 
Antiphospholipid antibodies can cause a variety of neurological deficits. Some of these disorders are caused by arterial thrombi while others are caused by cerebral emboli due to Libman-Sacks endocarditis. These antibodies are associated more frequently with focal manifestations, predominantly stroke syndromes. ,,
The most common presenting symptoms reported in ATM are numbness, parasthesiae, weakness of the legs, urinary retention, fecal incontinence, low back pain, midscapular and abdominal pain, and fever. 
In the case described, ATM was diagnosed on the basis of sudden onset of spastic paraparesis, loss of lower limb sensations with sensory level at D4 and sphincter disturbances in the absence of compressive lesions of the spinal cord.
During the episode of ATM in our patient, SLE was clinically inactive, although ANA and anti-DNA titers remained high (but comparatively much lower titers than earlier), normal C 3 and persistently low C4 levels [Table - 1]. It may be reminded that ATM developed while the patient was on cyclophosphamide and prednisolone. However, only after ATM developed were APL antibodies looked for, and found to be positive. Serologically active but clinically quiescent SLE has been described before, and such patients should be followed up and treated on the basis of clinical criteria. 
Lavalle et al  described strong association of APL antibodies in patients with SLE, developing transverse myelitis. Eleven out of their 12 patients with SLE were tested for anti-cardiolipin antibodies. All but one of their patients were positive, the one who was negative also had a positive VDRL and prolonged APTT coinciding with the episode of transverse myelitis. ,,,,,,, The authors postulated that APL may have a role in the pathogenesis of transverse myelitis in patients with SLE, possibly via vascular occlusion or by direct interaction with spinal cord phospholipids. They recommended that APL antibodies should be studied in all patients with transverse myelitis whether known to have SLE or not. In our patient, the APL was positive coinciding with the development of ATM keeping in agreement with these observations.
Barile et al  reported seven cases of ATM, one of whom had a full Devick's syndrome (optic neuritis plus transverse myelitis) and another developed optic neuritis after the ATM episode. However, our patient developed optic neuritis and then two months later transverse myelitis followed.
In our center, out of 87 patients diagnosed to have SLE between 1994 and 1999, this is the only case who developed ATM; the prevalence quoted in the literature is 3.2%. 
ATM occurred early in the course of disease and is in agreement with other studies. However, this complication tends to occur more in the older age group.  Moreover, cervical cord involvement is more common than thoracic and lumbar cord involvement. ,
MRI is the investigation of choice for the diagnosis and follow-up of transverse myelitis. Typical features are T1 and T2 signals prolongation, cord widening and contrast enhancement over several spinal segments.  However, in the patient described above, these typical abnormalities were not present.
Treatment of SLE related ATM remains controversial and steroids alone are insufficient in cases with focal and complex NPLE. Regimens used for treatment of diffuse proliferative lupus nephritis such as i.v. methylprednisolone pulses and cyclophosphamide are used by most investigators with satisfactory response and outcome. ,,
Our patient developed ATM while on monthly i.v. cyclophosphamide for six months and maintenance oral steroids as part of protocol for treatment of diffuse proliferative nephritis in our center.  She responded well to additional methylprednisolone pulse one gm i.v. for three days and plasmapheresis.
In conclusion, early diagnosis and prompt institution of methylprednisolone and i.v. cyclophosphamide are advocated in the treatment of ATM. However, further studies are required to delineate the best treatment option for short and long-term outcome.
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Ahmed H Mitwalli
Department of Medicine (38), King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
[Table - 1]