Non-compressive myelopathy: an unusual presentation of a patient with acute B lymphoblastic leukaemia

Abstract

A 21-year-old woman was admitted to the department of haematology with fever, generalised body ache and swelling of the feet. She also presented with band-like tightness over the abdomen and was unable to walk for the last 2 days. There was no history of trauma. She was diagnosed as a case of B-cell acute lymphoblastic leukaemia based on flow cytometry and bone marrow studies. MRI of the thoracolumbar spine revealed signal intensity alteration in the spinal cord from D1−2 to D5−6. Her serum vitamin B₁₂ and folate levels were normal. Autoimmune workup including antinuclear antibody and viral serology, and reverse transcriptase PCR for herpes simplex virus, Epstein-Barr virus and cytomegalovirus were negative. Her cerebrospinal fluid was negative for malignant cells. She was started on Berlin-Frankfurt-Munster 95 protocol and her condition improved along with partial improvement in the power of her limbs at the time of discharge. The neurological diagnosis of non-compressive myelopathy due to myelitis was considered.

Background

B-cell acute lymphoblastic leukaemia (B-ALL) is a common form of leukaemia occurring in children and young adults.¹ B-ALL can present with various atypical findings, with spinal cord involvement being one of them.^2–4 Spinal cord involvement and paraplegia/quadriplegia have been reported in the past which usually occurs due to spinal cord compression (SCC) caused by extradural/intradural mechanism.⁵ There is a scarcity of literature on non-compressive myelopathy caused by acute leukaemia. This case had an unusual non-compressive myelopathy which has not been reported previously.

Case presentation

A previously healthy 21-year-old woman was admitted to the department of clinical haematology with fever and generalised body ache for 3 months. She also presented with band-like tightness over the upper abdomen and was unable to walk for 2 days before admission.

She had fever which was low grade, on and off in nature, and used to decrease on taking medication. She also had generalised body ache that was present throughout day and night. There was no change in pain after change in position. Her condition progressively deteriorated over the past 3 months. There was gradual loss of power of both lower limbs. She was initially able to walk with support but became bedridden 2 days before admission. She also developed bladder and bowel involvement. There was no previous history of any trauma, significant illness, similar episode in the past, or any drug intake or addiction.

General examination was normal except mild pallor. The Examination of the central nervous system (CNS) revealed normal higher brain functions, no cranial nerve involvement and no signs of meningeal irritation. Weakness of both the lower limbs was seen (power 0/5), tone was decreased, deep tendon reflexes were normal and plantar reflex was bilateral extensor. There was no clonus. Loss of pain and temperature sensation was detected over the abdomen, below the costal margin. There was loss of bladder and bowel control. Deep tendon reflexes, tone and power in both upper limbs were normal. Examination of the abdomen, cardiovascular system, thorax, musculoskeletal system and breast was within normal limits.

Investigations

Investigations performed during the hospital stay are given in the table 1.

Table 1.

Investigations of the patient performed during hospital stay

Investigations	Results
Haemogram	Hb 93 g/L, TLC 37×109/L and platelets 60×109/L
Peripheral blood smear	Normocytic normochromic RBCs, leucocytosis with 60% blast cells and moderate thrombocytopenia
BM aspiration	Aparticulate yet acellular, megakaryocytes are markedly reduced, normal haematopoietic precursors are markedly reduced in number and 96% blasts
Flow cytometry	44% blast are gated in dim 45 vs low side scatter and were positive for CD10, CD38, CD 99, cCD79a, cCD22, CD19, CD20, CD34 and TdT
CECT scan head	No significant abnormality detected
CT scan thorax	Mild bilateral pleural effusion with compressive subsegmental atelectasis of underlying lung
MRI dorsolumbar spine	T2 WI (sagittal and transverse view) showing signal intensity alteration in the spinal cord extending from D1–2 to D5–6 vertebral levels (figures 1 and 2)
Serum folate	13.8 nmol/L
Serum vitamin B12	3000 pg/mL
CSF study	Negative for malignant cells
ANA and dsDNA	Negative
HSV, EBV and CMV by PCR	Negative

ANA, antinuclear antibodies; BM, bone marrow; CECT, contrast-enhanced CT; CMV, cytomegalovirus; CSF, cerebrospinal fluid; dsDNA, double-stranded DNA; EBV, Epstein-Barr virus; Hb, haemoglobin; HSV, herpes simplex virus; RBC, red blood count; TLC, total leucocyte count; WI, weighted images.

Figure 1.

MRI spine (sagittal view, T2 weighted image) of the patient showing demyelinating changes in spinal cord extending from D1–2 to D5–6 vertebral levels (shown by white arrows).

Figure 2.

MRI spine (transverse view, T2 axial image) of the patient showing demyelinating changes in spinal cord at D1–2 vertebral level (shown by white arrow).

Treatment

She was diagnosed as having acute B-cell lymphoblastic leukaemia with paraparesis due to non-compressive myelopathy. She was started on a high dose of methylprednisolone for 5 days along with Berlin-Frankfurt-Munster 95 (BFM-95) protocol for ALL with triple drug intrathecal therapy as CNS prophylaxis. Supportive treatment was given to manage bowel and bladder involvement.

Outcome and follow-up

There was gradual improvement in power after 1 month of therapy and she was able to move her legs on the bed (power 2/5), showing incomplete recovery. Bladder and bowel involvement persisted after induction chemotherapy. She is currently receiving induction-B as a part of BFM-95 protocol.

Discussion

Myelopathy is a devastating neurological complication of cancer. The resulting paralysis, pain and incontinence can turn a patient with cancer from a functioning individual to one who is confined to a chair or bed. SCC occurs in approximately 5% of patients with cancer (approximately 80 000 patients per year), mostly prostate, breast or lung cancer. In 20% of patients, SCC precedes the diagnosis of cancer, especially in patients with lung cancer.⁵

The patient presented with unusual findings like loss of power of lower limbs and not being able to walk from 2 days before admission; also, there was loss of bladder and bowel control. There was no evidence of cord compression (extradural or intradural). We did a PubMed search to look for more cases presenting with similar findings.

Myelopathy can occur in patients due to various reasons. It may present with compressive or non-compressive causes. Compressive causes may be traumatic, infectious, degenerative, vascular or malignant conditions. Non-compressive causes include viral infections such as varicella zoster, Epstein-Barr, herpes simplex, HIV and others; various bacterial infections; acute disseminated encephalitis; metabolic derangements; toxic substance intake; vascular events and autoimmune conditions.⁶

ALL is a common form of leukaemia occurring in children and young adults.¹ Spinal cord involvement is not usually seen in patients of acute leukaemia.² There are only few case reports mentioning involvement of the spinal cord in acute leukaemia. Non-compressive causes of spinal cord involvement are rarely seen in acute B-cell leukaemia. In a study published by Prabhakar et al,⁷ which comprised 57 patients (42 men and 15 women) having non-compressive myelopathy due to different causes, it was seen that acute transverse myelitis was most common, followed by vitamin B₁₂ deficiency myelopathy in a non-leukaemic setup.

Similarly, a case report published in 2001, showed that ALL initially presented as transverse myelopathy. The case presented with back pain and inability to walk 5 months before being diagnosed as a case of ALL.⁴

In another case report, a patient with acute myeloid leukaemia presented with sudden-onset bilateral lower extremity paralysis. It was seen in a relapsed case of acute myeloid leukaemia that had disseminated mucormycosis. Postmortem examination revealed that the duramater of the spinal cord was also involved, leading to paralysis.⁸

Conclusion

Myelopathy may lead to paralysis, pain, incontinence and decrease the performance status of the patient drastically. Acute B-cell leukaemia rarely presents with non-compressive myelopathy but one should be careful to keep in mind this unusual presentation. There should not be any evidence of cord compression, autoimmune disorders, nutritional deficiency of B₁₂ or folic acid, or any viral pathology. Early initiation of high-dose steroid is necessary for rapid response and better prognosis. Bladder and bowel involvement at the time of presentation predicts poor outcome in such cases.

Learning points.

• Acute leukaemia can present upfront with various atypical findings.

• Non-compressive myelopathy is largely unknown but can occur in acute lymphoblastic leukaemia.

• All possible causes of non-compressive myelopathy should be ruled out before labelling it as a leukaemia-associated finding.