Eur J Pediatr (1995) 154:815-818 9 Springer-Verlag 1995 S i o b h a n M. G o r m a l l y William Bourke Barry K i e r s e Hugh Monaghan Joe M c M e n a m i n Brendan Drumm Received: t8 August 1994 Accepted: 7 March 1995 S. M. Gormally 9W. Bourke. B. Kierse H. Monaghan - J. McMenamin Department of Paediatrics, University College Dublin, Ireland B. Drumm (EN) Department of Paediatrics, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland Te.: (01)45569101 Fax: (01)4555307 isolated cerebral thrombo-embolism and Crohn disease Abstract Arterial t h r o m b o - e m b o l i s m is an unusual c o m p l i c a t i o n in i n f l a m m a t o r y b o w e l disease in adults and children. Cerebral arterial disease has b e e n reported on only a few occasions. There are only two previous case reports o f arterial disease occurring in a child with C r o h n disease. H o w e v e r in both instances the arterial disease was part o f a generalised Takayasu arteritis w h i c h resulted in m u l t i - o r g a n i n v o l v e m e n t . This report describes a 14-year-old b o y w h o d e v e l o p e d seizures before a h i s t o l o g i c a l diagnosis o f Crohn disease was made. These seizures were Introduction C r o h n disease is a chronic, transmural, i n f l a m m a t o r y process affecting any part o f the b o w e l f r o m m o u t h to anus in a discontinuous fashion [6, 7]. H i s t o l o g i c a l l y it is characterised b y the presence o f n o n - c a s e a t i n g granuloma. It has an overall incidence o f 3.5 p e r 100,000 with a p r e v a l e n c e of 46 p e r 100,000 [2, 4, 5, 14]. Children with Crohn disease m a y present with n o n s p e c i f i c extra-intestinal manifestations and g r o w t h retardation [16]. T h r o m b o - e m b o l i c p h e n o m e n a are a rare, but well-documented c o m p l i c a t i o n o f i n f l a m m a t o r y b o w e l disease (IBD) in adults [1, 3, 8, 17, 18]. The majority involve venous t h r o m b o - e m b o l i s m . There have been few case reports of children with vascular complications o f IBD [9, 12, 13, 15, 20]. There are two reports of arterial disease occurring in children with Crohn disease [20, 22] but in both of these cases i n v o l v e m e n t was associated with a generalised Takayasu arteritis, which affected m a n y major arteries. the result of a vascular lesion which was confined to the right m i d d l e cerebral artery. K e y w o r d s Crohn disease C h i l d h o o d 9 Cerebral t h r o m b o e m b o l i s m . Seizures A b b r e v i a t i o n IBD i n f l a m m a t o r y bowel disease W e report the occmTence o f an isolated cerebral arterial t h r o m b o - e m b o l i s m in a b o y with Crohn disease. Case report A 14-year-old boy was referred to the Gastro-enterology Department with a 5-month history of abdominal pain, weight loss, lethargy and anorexia. He had intermittent "red eyes" which were not painful. There was no family history of gastro-intestinal disease. Examination revealed a pale, cachectic boy whose weight of 36 kg was less than the 3rd percentile and who had clubbing. He had lower abdominal tenderness. A clean perianal fissure and two skin tags were noted. A decision was made to admit him over the following week for an upper and lower endoscopy to rule out IBD. Three days later he was admitted to the hospital with a history of sudden onset right-sided headache. This was associated with a diminution in vision to the left. Subsequently he had two generalised tonic-clonic seizures. On examination he was drowsy, his pupils were equal and reacting to light and there was no papilloedema or neck stiffness. He was moving all limbs spontaneously but had generalised hypotonia and hyporeflexia. There were no localising signs. 816 He was admitted to hospital and over the following 12 h he had five convulsions beginning on the left side with generalisation. His eyes were consistently deviated to the left between seizures. Twelve hours post admission he developed status epilepticus. Investigations revealed a Hb 13.8 g/dl, white cell count 28.1 x 109/1 (87.6% grannlocytes), platlet count 517 x 109/1, plasma viscosity 1.53 mPa (normal values -- 1.5-1.72 mPa) and an ESR of 60 mm/h. Prothrombin time, partial thromboplastin time, calcium, magnesium, urea and electrolytes were all normal. CSF was clear and colourless, with one white cell, 4 red cells per mm 3 and protein content of 0.2 h/l. A toxicology screen was negative. A computed tomography of the brain on the night of admission was normal. The seizures became intractable over the next 8 weeks, during which he was treated with intravenous phenytoin, phenobarbitone and paraldehyde. Intermittent Positive Pressure Ventilation was required due to the respiratory depressive effect of the anticonvulsant medication. EEG initially showed continuous bilateral and generalised spike wave activity without lateralisation, intermixed with periodic flattening. Subsequently studies confirmed periodic lateralising epileptiform discharges mainly over the right hemisphere. Neurological examination now revealed hypotonia in the left upper and lower limbs, and paucity of movements with a left facial weakness. When seizures eventually subsided with a chlormethiazole infusion, a dense residual left hemiplegia was apparent. A cerebral angiogram performed 4 weeks after admission showed a significant reduction in the calibre of the ascending prerolandic branch of the right middle cerebral artery consistent with tbromboembolic occlusion (Fig. 1). Repeated upper endoscopy and colonoscopy revealed a normal intestinal mucosa. Multiple gastro-intestinal biopsies were obtained from the stomach, duodenum, small bowel and colon. However histological evidence of inflammation was not identified. A barium meal showed dilated loops of jejunum with coarsening of mucosal folds. Ophthalmological examination showed no evidence of retinal vasculitis. A decision was made to treat the patient empirically as having Crohn disease using corticosteroids (intravenous hydrocortisone 4 mg/kg/dose 4-hourly followed by prednisolone 1 mg/kg/day 50- 45, 0 40 35 30 ; 5; 1; MONTHS Fig.2 Patient's weight over a 15-month period following initial presentation. An elemental diet consisting of 2400 kcal/day began at 2 months. The diet was discontinued at 6 months and reinstituted at 10 months orally when tolerated), total parenteral nutrition and subsequently an elemental diet. This tentative diagnosis of Crohn disease was supported by a dramatic response to such treatment. His weight increased to 52 kg over a period of 4 months and this was associated with a marked improvement in symptomatology. The abdominal pain resolved and there was an improvement in energy level and appetite. A temporary lapse in compliance with the elemental diet post discharge was associated with a recurrence of anorexia, abdominal pain and weight loss. These symptoms disappeared following reinstitution of the elemental diet (Fig. 2). A programme of physical and occupational therapy was instituted. The patient's hemiplegia improved over a 6-month period. However, 18 months after presentation he continues to have a marked left hemiparesis with improvement over the past year. Eight months after initial presentation a further colonoscopy was performed. Although bowel mucosa appeared normal, a noncaseating granuloma comprising of epitheloid cells, activated histiocytes and multinucleated giant cells, consistent with Crohn disease, was identified in a biopsy specimen taken from the caecum (Fig. 3). Discussion Fig. 1 The lateral carotid angiogram shows poor opacification of the ascending pre central branch of the middle cerebral artery consistent with proximal embolic/thrombotic occlusion E x t r a - i n t e s t i n a l s y m p t o m s are w e l l - k a l o w n in C r o h n dise a s e a n d m a y be t h e p r e s e n t i n g f e a t u r e s o f the disease. C l a s s i c a l l y t h e y c o m p r i s e o f g r o w t h failure, d e r m a t o l o g i cal, ocular, s k e l e t a l and h e p a t o b i l i a r y m a n i f e s t a t i o n s . Vasc u l a r e v e n t s in I B D are rare. T h e r e are, to o u r k n o w l e d g e , ten c a s e reports o f t h r o m b o - e m b o l i c e v e n t s in c h i l d r e n w i t h I B D - s e v e n o f t h e s e o c c u r r i n g in a s s o c i a t i o n w i t h u l c e r a t i v e colitis. T h e r e are t h r e e p u t a t i v e c a s e s r e p o r t e d in a s s o c i a t i o n w i t h C r o h n d i s e a s e (Table 1). T w o p a t i e n t s w e r e d e s c r i b e d b y Y a s s e n g e r et al. [22] and Van E l b u r g et al. [20]. In b o t h cases, arterial i n v o l v e m e n t w a s part o f a 817 Fig.3 Histology ofbiopsy from caecum, showing a well formed epitheloid granuloma (arrow) in a lymphoid aggregate in the lamina propria Table 1 Vascular complications in children with Crohn disease Reference Age Sex Vascular involvement CNS Outcome Yassinger 15 et al. [22] F Muitiplelarge Hemiparesis Resolved vessel stenosis Van Elburg 14 et al. [20] F Multiplelarge None vessel stenosis Gormally et al. (present report) M Right middle Hemiplegia Marked cerebral artery hemiparesis narrowing 14 generalised Takaysu arteritis involving other major arteries in the body. The case reported by Van Elburg et al. [20] was similar to ours in that the histological diagnosis of Crohn post-dated the vascular involvement. A third case report by Lloyd-Still and Tomasi [12] while interesting, cannot be included in this group. These authors described a 3-month-old baby with a diagnosis of "enterocolitis" who simultaneously had intractable seizures and mental retardation. No angiographic studies were performed and at post-mortem, typical histological features of Crohn disease could not be detected. The cause of vascular complications in IBD is unknown. There is speculation that they may be related to a hypercoagulable state. Haemostatic alterations include thrombocytosis, platelet dysfunction, increased levels of fibrinogen, factors V and VIII and a decrease in an- tithrombin III activity but these have not been consistently identified [10, 11]. The exact pathological process involved in these vascular events has not been established. Necrotising vasculitis, Takayasu arteritis and giant cell arteritis have all been implicated [19, 22]. Takayasu arteritis would certainly explain the widespread involvement of arteries as described in the two previous reports [20, 22]. Histological examination of the arteries was not performed in this case therefore one can only speculate about the aetiology of the arterial lesion. The fact that arterial involvement was so localised makes Takayasu arteritis unlikely. Giant cell arteritis must be a possible underlying pathology as this is a patchy granulomatous inflammation that effects medium-sized arteries anywhere in the body [19, 21] and has a predilection for cranial arteries. Cerebral arterial lesions in IBD can have catastrophic consequences. The widespread involvement of other major arteries has hitherto provided some clue to the underlying process in a child with IBD presenting with seizures. The vascular lesions in this case were confined solely to the right middle cerebral artery. It is of clinical importance therefore to be aware of the fact that neurological symptoms in IBD can be secondary to isolated cerebral vasculopathy and are not always accompanied by a widespread arteropathy as previously described. Acknowledgements We wish to acknowledge the help of Dr. J. Toland, Consultant Neuroradiologist, Beaumont Hospital, Dublin, in interpreting the angiographic study and to Ms. Sharon Keamey for typing the manuscript. 818 References 1. 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