Title: Bilateral Lower Limb Weakness in Acute Severe Ulcerative Colitis

Ruairi W Lynch MBChBDepartment of Gastroenterology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU

Timothy Soane PhDDepartment of Neurology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU

Rod Gibson MBChBDepartment of Neuroradiology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU

Suvankar Pal MDDepartment of Neurology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU

Corresponding author: Charlie W Lees PhDDepartment of Gastroenterology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XUE-mail: Charlie.lees@ed.ac.uk

An obese 49-year-old male with no significant past medical history presented to hospital in August 2014 with a 5 week history of bloody diarrhoea, anorexia and weight loss (pre-morbid weight: 99.8 kg; body mass index: 33.4kg/m2). On admission he was passing 20 bloody stools/24hrs with nocturnal disturbance, pyrexia, tachycardia, anaemia and a robust inflammatory response. Flexible sigmoidoscopy demonstrated a severe confluent colitis and pathology confirmed a first presentation of active ulcerative colitis (figure). Given these findings we commenced intravenous methylprednisolone 30mg BD for 7 days which was subsequently converted to a standard reducing course of oral prednisolone (40mg daily, decreasing by 5mg/week). Given only a partial response to steroid therapy, we started rescue therapy with ciclosporin on day 5. This effected an excellent response with stool frequency, serological markers and observations all normalising by discharge on day 11.

He represented just over one month later with progressive gait disturbance, falls, lumbar pain and a feeling of a tight band around his torso. He denied any history of urinary retention/incontinence or bowel incontinence; he did however report new erectile dysfunction. There was no history of fever, spinal trauma and no previous relevant neurological symptoms. He was taking 15mg/day of prednisolone and had received, in total, 45 days of steroids. His colitis remained in excellent clinical and biochemical remission on oral ciclosporin.

On examination he had a moon face consistent with Cushing’s syndrome and walked with the assistance of two crutches. Tone was increased in both lower limbs with a symmetrical pattern of pyramidal weakness (MRC Grade 4+/5). Lower limb deep tendon reflexes were pathologically brisk bilaterally: knee jerk 3+, ankle jerk 4+ with non-sustained bilateral ankle clonus. Joint position sense was impaired distally in the lower limbs and plantar responses were equivocal. Sensory examination revealed a sensory level to light touch and pin-prick below T10 with reduced vibration sensation to the 10th rib. Examination of his spine was unremarkable.

Blood results (normal range) suggested that an intrinsic cause of myelopathy such as infection, vitamin B12 or copper deficiency were less likely: haemoglobin: 124g/L (135-180); white cell count: 10.8x109/L (4.0-11.0); platelets: 229x109/L (150-400); normal renal and liver function; CRP<1mg/L (<5); vitamin B12: 241pmol/L (133-1476); copper: 13.1umol/L (10-22). There was no evidence of impaired glucose tolerance. A MRI spine demonstrated an epidural mass from T1 through T11, with further epidural deposits in the sacral region (figure). The mass was completely suppressed on STIR imaging and was uniformly bright on both T1 and fast spin echo T2 images. This appearance is only consistent with fat and given its diffuse distribution could only represent lipomatosis.

The extensive nature of the spinal cord compression rendered surgical debulking inappropriate as this would have involved a T1-L2 decompressive laminectomy followed by pedicle screw fixation and direct excision of the lipomatosis. This would have carried a very significant risk of blood loss and morbidity as well as exacerbation of lumbar spinal back pain. We therefore opted for conservative management: a rapid tapering of his steroids over 7 days; pregabalin for neuropathic pain; physiotherapy and dietician review to aid weight loss.

Interval MRI (5 months later) demonstrated partial resolution of the spinal lipomatosis with compression extending from T6 - T9 and no intrinsic cord signal abnormality. He continued to improve gradually and in October 2015 had only residual decreased sensation in his toes and normal power throughout, however he continued to walk with the aide of walking sticks.

Spinal Epidural Lipomatosis (SEL) is the pathological overgrowth of physiological fat tissue in the extradural space leading to spinal cord compression. It is uncommon, having only been reported twice previously in inflammatory bowel disease.1,2 It can be a complication of prolonged corticosteroid treatment (55.3% of cases) but rarely presents acutely with as short a period of treatment as we report.3,4 24.5% of cases reported are attributed to obesity alone3 and pertinently the higher level of background extradural fat seen in obese patients may predispose to a shorter time of onset in corticosteroid induced SEL.5 17% of cases have no identifiable cause and there are no previous reports of ciclosporin causing SEL.

25% of reported cases involving steroids are treated conservatively with removal of exogenous steroids and weight loss.3 Surgical laminectomy with debulking has been more frequently reported as an alternative treatment (75% of cases) and has a similar reported response rate to conservative management (77%).3 There is, however, a paucity of reports in patients with as extensive SEL as presented here; given this and the significant risks outlined above we adopted a conservative approach.

Our case is particularly noteworthy due to the extent of disease on MRI and the speed of onset of symptoms. Steroids remain the mainstay of treatment in many medical conditions and indeed they remain life-saving in acute severe ulcerative colitis. However, in the setting of an increasingly obese population, SEL is an important albeit rare complication to consider.

Figure: Spinal lipomatosis in a patient with acute severe ulcerative colitis (A) Endoscopic image of sigmoid colon demonstrating severe colitis. (B) T1 weighted MRI scan of spine. Sagittal view of the cervical and thoracic spine shows spinal epidural lipomatosis with compression T1–T9 (arrow).

1. Kotilainen, E., Hohenthal, U., Karhu, J. & Kotilainen, P. Spinal epidural lipomatosis caused by corticosteroid treatment in ulcerative colitis. Eur. J. Intern. Med. 17, 138–140 (2006).

2. WE. George, M Wilmot, A Greenhouse, M. H. Medical Management of Steroid-Induced Epidural Lipomatosis. N. Engl. J. Med. 308, 316–319 (1983).

3. Fogel, G. R., Cunningham, P. Y. & Esses, S. I. Spinal epidural lipomatosis: case reports, literature review and meta-analysis. Spine J. 5, 202–211 (2005).

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4. Tobler, W. D. & Weil, S. Epidural lipomatosis and renal transplantation. Surg. Neurol. 29, 141–144 (1988).

5. Koch, C. A., Doppman, J. L., Patronas, N. J., Nieman, L. K. & Chrousos, G. P. Do Glucocorticoids Cause Spinal Epidural Lipomatosis ? When Endocrinology and Spinal Surgery Meet. 11, 86–90 (2000).

Contributors: Ruairi W Lynch: Gastroenterology registrar review at time of re-admission, drafting of manuscript, figures and literature search. Joint first author.Timothy Soane: Neurology registrar review at time of re-admission, drafting of manuscript, figures and literature search. Joint first author.Rod Gibson: Consultant radiologist responsible for reporting of radiology, critical review of manuscript.Suvankar Pal: Consultant neurologist in charge of patient’s care, critical review of manuscript.Charlie W Lees: Consultant gastroenterologist in charge of patient’s care, critical review of manuscript.

Conflict of interests: None to declare.