J7ournal ofNeurology, Neurosurgery, and Psychiatry 1996;60:225-230 225 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from CLINICOPATHOLOGICAL CASE CONFERENCE

Progressive ataxia, focal , and malabsorption syndrome in a 41 year old woman

Colin J Mumford, Nicholas A Fletcher, James W Ironside, Charles P Warlow

Case presentation twitching of the left side of the face and a stac- The patient was a right handed woman, born cato dysarthria which was exacerbated by the in 1952 and married. She was a radio taxi con- twitching movements of her mouth. There was troller. mild incoordination of the lower limbs but In October 1993 she presented to her local with full power on formal testing, and no sen- district general hospital having had two short sory abnormalities, normal tendon reflexes, lived episodes of involuntary twitching of the and bilateral flexor plantar responses. She was left side of her face and then a third episode of able to walk unaided but unsteadily. left sided facial twitching which was followed Her haemoglobin content was 11 1 g/dl by collapse and a generalised tonic clonic with a moderate macrocytosis and a mean cor- . Nine months previously she had been puscular volume of 104 fl (normal 78-98 fl); a investigated and treated for a right upper raised platelet count at 609 x 109/1 (normal pulmonary abscess, from which the causative 150-400 x 109/l); and a white cell count of organisms were not isolated. She had no other 5-4 x 109/l (normal 4-11 x 109/l). The dif- relevant medical or family history. She did not ferential white count was essentially unre- smoke. A contrast enhanced cranial CT was markable although some neutrophils showed unremarkable. She had macrocytic anaemia toxic granulation and occasional myelocytes and abnormal liver function. Further investi- were seen on a blood film. Erythrocyte sedi- gations included a liver biopsy, which showed mentation rate was 20 mm/hour. The urea, widespread fatty change, and a jejunal biopsy electrolytes, including calcium and magne- which showed total villous atrophy with crypt sium, and plasma glucose were normal. Her hyperplasia. She was established on a gluten liver function tests were deranged with an free diet and given drugs, ini- ALT of 108 U/l (normal 5-59 U/l), alkaline tially but this was subsequently phosphatase 233 U/l (normal 30-140 U/l); changed to after she developed yGT 159 U/l (normal 6-31 U/l). Thyroid a rash. function tests were normal. Serum angiotensin http://jnnp.bmj.com/ Despite anticonvulsant medication, be- converting enzyme was 106 U/l (normal tween late 1993 and early 1994 she continued 37-75 U/l). A T2 weighted MRI showed multi- to have intermittent episodes of predominantly ple areas of high signal scattered diffusely left sided facial twitching but no further gener- throughout the cerebral white matter (fig 1). alised seizures. Her speech became slurred There were also abnormal areas of high signal and her gait increasingly unsteady. In March in the midbrain (fig 2). Lumbar puncture

1994 examination showed a thin, pale woman. showed an opening pressure of 11 cm CSF. on September 30, 2021 by guest. Protected copyright. A smooth non-tender liver edge was felt 2 cm No red cells were seen and there was 1 lym- Department of Clinical below the costal margin. Neurological exami- phocyte/mm3. Protein in CSF was raised at Neurosciences nation C J Mumford showed repeated episodes of rapid 0-7 g/l (normal 0-15-0-45 g/l). The CSF glu- C P Warlow Neuropathology Laboratory, Western General Hospital, Edinburgh EH4 2XU, UK J W Ironside The Walton Centre for and Neurosurgery, Liverpool, L9 IAE, UK N A Fletcher Correspondence to: Dr Colin Mumford, Department of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Figure 1 T2 weighted cranial MRI showing multiple Figure 2 T2 weighted MRI section showing abnormal Received 27 September 1995 areas ofhigh signal scattered diffusely throughout the white area of high signal in the left midbrain. Accepted 4 October 1995 matter. 226 Mumford, Fletcher, Ironside, Warlow J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from cose was 3 4 mmol/l (simultaneous plasma ration and died on 18 October 1994. A post- glucose 6-1 mmol/l). Cytological analysis of mortem examination was performed. CSF was unremarkable. A chest radiograph suggested scarring in the right hemithorax and thoracic CT confirmed this area of scarring Discussion situated posteriorly in the right upper lobe. DR N A FLETCHER There was no evidence of cavitation or gener- Nine months before the onset of her neurolog- alised pulmonary parenchymal disease. Two ical illness this woman had developed a right EEGs were similar and showed "frequent non- upper lobe lung abscess, from which she convulsive runs of discharges". A recovered. The abscess could have been due to further jejunal biopsy showed "severe partial several causes including tuberculosis, although villous atrophy" after she had been on a gluten the recovery was very rapid for that condition; free diet for eight weeks. other possibilities include a Klebsiella pneu- The carbamazepine was gradually replaced monia and other infectious agents which with clonazepam with reduced facial twitch- would question whether her immune status ing. She was discharged on a combination of was normal. However, she improved and then clonazepam and multivitamins including vita- developed two episodes of left sided facial min E, thiamine, and folate. twitching, and then another event which was Although she had seemed initially to followed by a secondarily generalised seizure. respond to clonazepam she required readmis- This tells us that there was a discharging corti- sion at the end of April 1994 with increasingly cal focus, because a subcortical abnormality frequent episodes of facial twitching, which would be unlikely to be followed by a gener- was now bilateral, and worsening unsteadiness. alised seizure. She was treated appropriately Examination showed bilateral facial twitching but did not improve. It then became clear that which had become continuous. Her speech she was developing a progressive neurological was very jerky. She had a symmetric postural illness, because between October 1994 and of both hands but strength and sensa- March 1995, a period of only five months, she tion were preserved. There were mild bilateral developed progressive twitching of the left side cerebellar signs with finger to nose and heel to of her face, slurred speech, and limb and gait shin ataxia, plus gait ataxia. The reflexes ataxia. Her liver was enlarged. The slurred remained unremarkable with flexor plantars. speech may have been due to cerebellar dys- Two further EEGs were performed which function or . The best clinical clue remained abnormal with frequent runs of bilat- to differentiate these is the eye movements, eral high voltage delta wave activity. because if mycolonus is severe, the speech may was introduced instead of clonazepam with become jerky. Although we are not told about improvement of the twitching. the eye movements here, I suspect that her However, her clinical condition continued speech problem was mainly cerebellar, to deteriorate and in June 1994 she looked because she had additional limb and gait thin and unwell. She had oral candidiasis. ataxia. Clearly there was a systemic illness as Continuous bilateral facial twitching persisted. well. She seemed to have a gaze preference to the She deteriorated further, becoming more right. There was mild global weakness of all unsteady, with bilateral facial twitching, cere- four limbs. Reflexes and plantars remained bellar signs, and a postural tremor. Tremor in http://jnnp.bmj.com/ unchanged and there was persistent cerebellar patients like this can be confusing because ataxia. Haematological investigations were patients with myoclonic disorders may have largely unchanged from previous analyses. fine myoclonus of the fingers, mimicking a With the patient's consent an HIV test was postural tremor. She was switched to performed and this was negative. The CSF clobazam, but became worse over the next two was re-examined and on this occasion the months, developing oral candidiasis, more

results were all normal with unremarkable pronounced bilateral facial twitching and a on September 30, 2021 by guest. Protected copyright. cytology. She had further CT of the thorax gaze preference to the right, global weakness, this time including the upper abdomen, and and cerebellar signs. She was clearly very this was normal. A four vessel cerebral unwell, so the presence of oral candida does angiogram was normal. not necessarily point to disturbed immune Despite further attempts at treatment with function. The gaze preference to the right , broad spectrum antibiotics, could indicate a brain stem or cerebral lesion, and intravenous methyl prednisolone, she but she seems to have had a multifocal neuro- entered a rapid decline such that by the end of logical illness. August 1994 she was effectively confined to Between June 1994 and August 1994 she bed. The findings on examination had became confined to bed and dysphasic, indi- changed. She had become dysphasic. She had cating some left sided cortical or subcortical bilateral sustained nystagmus, most pro- involvement. Lateral gaze nystagmus and nounced on right lateral gaze. Palatal move- palatal weakness point to involvement of the ment was poor. She had developed an brainstem, and she had a spastic tetraparesis. asymmetric spastic tetraparesis more pro- At this point the key question was to decide nounced on the right. She had pathologically on the nature of the facial twitching. (Dr brisk reflexes with bilateral extensor plantars. Fletcher had available a video of the facial She had frequent generalised seizures. She movements.) The twitching involved the developed a chest infection and despite full whole of the side of her face, was fine, irregular, supportive measures continued a rapid deterio- and worse when she spoke. These movements Progressive ataxia, focal seizures, and malabsorption syndrome in a 41 year old woman 227 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from could be given several names-for example, stage than in this case. Kufs disease (neuronal focal motor seizures or even epilepsia partialis ceroid lipofuscinosis)8 is an adult onset disor- continua. A specialist in movement disorders der which may be sporadic or familial, with might call them focal cortical myoclonus, but characteristic lipofuscin deposits in the ner- this is due to a paroxysmal discharge of cortical vous system which may be diagnosed by liver neurons, and therefore is a fragment of or rectal biopsies. The condition is similar to . My interpretation of these move- some of the forms of Batten's disease affecting ments is bilateral (multifocal) cortical children. Sialidosis type 19 can be excluded, myoclonus. This is not a form of subcortical because patients have a cherry-red spot at the focal myoclonus, which is more commonly macula, not present in this case. Biotin regular and rhythmical, such as palatal responsive ,8 due to biotinidase myoclonus. I would mention oculomasticatory deficiency, usually occurs in much younger myoarrhythmia, which is a peculiar movement patients, although there are a few reports of disorder with possible relevance to this case, as adults who develop acquired biotin deficiency the patient had gastrointestinal symptoms; this as a result of intestinal malabsorption, and get a is pathognomonic of cerebral Whipple's dis- myoclonic ataxic syndrome. Gaucher's dis- ease,1 and is a rhythmic oscillation of eye and ease8 and the rare "action-myoclonus/ jaw movements at around 1 Hz, associated renal failure" syndrome8 are both very unlikely with impaired conscious level, vertical eye here. movements, and sometimes a complete oph- Moving on to the investigations: the CT thalmoplegia, and the condition reflects a ros- was normal, she was anaemic, and liver func- tral midbrain lesion. This woman's facial tion was deranged, with a biopsy showing fatty appearance did not have the features of that change. This last feature tends not to occur in condition. malabsorption syndrome and makes me sus- In summary, the clinical features showed a pect that she consumed a large quantity of rapidly progressive multifocal neurological ill- alcohol. The jejunal biopsy showed total vil- ness over 10 months, with cortical, brainstem, lous atrophy, a severe lesion, with crypt hyper- and cerebellar involvement, leading to ataxia, plasia, entirely consistent with coeliac disease. prominent facial twitching, seizures and the The macrocytic anaemia would be consistent later development of corticospinal tract signs. with both folate deficiency and alcohol excess. The clinical differential diagnosis must include I doubt whether this is vitamin B 12 deficiency, the Ramsay-Hunt syndrome,2 which is a het- because people with coeliac disease tend to erogeneous disorder comprising progressive absorb B 12 relatively well. There were myelo- cerebellar ataxia as a prominent feature, cytes and toxic granulation on the blood film, myoclonic twitching, and seizures, possibly and the chest radiograph was normal with no with the development of other neurological evidence of any active lung disease. The liver signs later on; it presents as a myoclonic function was non-specifically deranged with ataxia. At times the seizures and the raised y-glutamyl transferase, perhaps due to myoclonus are much more prominent than the alcohol, although abnormal liver function tests cerebellar features, and this is sometimes are occasionally seen in coeliac disease. The referred to as progressive . CSF protein was raised, which is difficult to

If we accept that this patient had progressive interpret, and the EEG was highly abnormal http://jnnp.bmj.com/ ataxia with myoclonus and seizures, and with frequent runs of high amplitude sharp accept this as a form of the Ramsay-Hunt syn- and slow wave activity which looked like drome, then among the conditions to consider seizure discharges, and intervening periods are spinocerebellar degenerations, such as where the background rhythm only looked Unverricht-Lundborg disease (a recessively mildly slow. The repeat jejunal biopsy, after inherited early onset ataxia sometimes called only eight weeks of a gluten free diet showed Baltic or Mediterranean myoclonus),34 and severe partial villous atrophy, probably not dentatorubropallidoluysian atrophy,5 which is very disimilar to the initial biopsy. A delay of on September 30, 2021 by guest. Protected copyright. autosomal dominant and may present in adult several months or perhaps a year would be life with myoclonus and ataxia. A clear family needed to see a real improvement in such a history would be expected with this disorder. biopsy, even after dietary gluten exclusion in should be considered, coeliac disease. especially myoclonic epilepsy with ragged red Magnetic resonance imaging showed multi- fibres (MERRF),6 but the progression seems focal lesions scattered through the cerebral too rapid for this or a spinocerebellar degener- hemispheres with a predominant subcortical ation. It has recently been emphasised that distribution, with many lesions in the brain- coeliac disease can cause this syndrome,7 and stem and thalamus. There were lesions in both it has been suggested that any patient present- white and grey matter, so this was not a purely ing with the Ramsay-Hunt syndrome that is, white matter disease, and there was prominent progressive ataxia and myoclonus should brainstem and diencephalic involvement. have a jejunal biopsy specifically to look for There are a few other relevant tests: we know coeliac disease. Whipple's disease has already she was HIV negative, CT of chest and been mentioned as a condition that may pre- abdomen were uninformative and the cerebral sent in this way, sometimes diagnosed by angiogram, I imagine looking for the "bead- intestinal biopsy, but sometimes only on post- ing" of vasculitis was unremarkable, although mortem examination of the brain. There are that would not entirely exclude the condition. several rarer conditions to mention. Lafora There was a curious MRI appearance with body disease8 would develop at a much earlier multifocal lesions mainly in the brainstem, 228 Mumford, Fletcher, Ironside, Warlow J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from cerebellum, and diencephalon, but we know that there is cortical involvement in this case because of the epilepsy and the dysphasia. There was the recent lung abscess, intestinal malabsorption which appears to be due to coeliac disease, the megaloblastic anaemia, fatty infiltration of the liver, raised angiotensin converting enzyme activity which may have numerous causes apart from just sarcoidosis, but this should perhaps be considered here. Figure 3 Small bowel biopsy showing subtotal villous The MRI might fit with sarcoid, but the clinical atrophy with crypt hyperplasia. An increased number of chronic inflammatory cells are present in the lamina presentation would be very unusual, and CSF propria, with numerous intraepithelial lymphocytes. The abnormalities and meningeal involvement appearance is consistent with a diagnosis of coeliac disease. would be expected in neurosarcodosis that was bad enough to have prominent epileptic activity DR J W IRONSIDE and to be fatal. The neutrophilic changes are The first small bowel biopsy from this patient non-specific, and would fit with either inflam- confirmed an abnormal mucosal pattern with mation or infection, and the raised platelet subtotal villous atrophy with crypt hyperplasia, count can be attributed to hyposplenism increased inflammatory cells in the lamina which commonly accompanies intestinal mal- propria, and intraepithelial lymphocytes, find- absorption. ings consistent with coeliac disease (fig 3). In summary, this is progressive ataxia with These features were largely unchanged on the myoclonus and epilepsy-that is, a "Ramsay- second biopsy. Hunt" or progressive myoclonic epilepsy type The necropsy was performed shortly after neurological syndrome with unusual facial death, and the most striking findings were in movements which seem to be myoclonic. The the abdomen with abnormal enlarged rounded crux of the case hinges on whether the intestinal lymph nodes scattered within the mesentry. biopsy findings are considered to be relevant to When I saw this I wondered about lymphoma the case or not. I imagine that they must be rel- or infection, but sections showed cavitation evant and should therefore be taken seriously, within the lymph nodes which were full of pale especially as there is an association between sterile acellular proteinaceous material, an coeliac disease and this type of neurological ill- unusual finding called the "mesenteric lymph ness. We should consider an immunodefi- node cavitation syndrome."' The lymphatic ciency state, as this can also cause small bowel vessels around the small bowel were also full atrophy (acquired hypogammaglobulinaemia of this proteinaceous fluid as part of the same or variable immunodeficiency may cause syndrome. There was evidence of extensive recurrent infections and a bowel appearance coeliac disease in the upper small bowel with similar to coeliac disease). Obviously a small no sign of tumour, infection, or Whipple's dis- bowel lymphoma associated with coeliac dis- ease. There was the expected gross splenic ease could have spread to the , atrophy, the organ weighing only 20 g. In the but this would be an unusual presentation. lungs there was florid bronchopneumonia (the and infestations of the bowel, and immediate cause of death), and scarring from

Infections http://jnnp.bmj.com/ tropical sprue could give a similar histological the old abscess, but no sign of tuberculosis, appearance, but it would be difficult to link calcification, or tumour. these to this neurological presentation. The brain weighed 1270 g, a little less than Accordingly this neurological illness is proba- expected for a patient of this age. At first bly due to the coeliac disease. glance, there did not seem to be much wrong, Turning to the reported neurological com- either internally or on cross section, but closer plications of coeliac disease, there have been examination showed a rather flecked appear- reports of a fatal neurological illness associated ance of the white matter, with small areas of on September 30, 2021 by guest. Protected copyright. with coeliac disease, characterised by progres- discolouration at the junction of the grey and sive cerebellar ataxia, myoclonus, epilepsy, white matter in the cerebral cortex (fig 4). peripheral neuropathy, pyramidal tract signs, tremor, and brain stem features,"' 12and the key point is that this neurological syndrome did not respond to the withdrawal of dietary gluten. The mucosal lesion in the small bowel did improve, but the neurological features did not. Pathologically there was reported to be extensive and neuronal loss in a multifo- cal and patchy way, involving the cerebellum, deep grey matter, and brainstem nucleii, with focal cortical lesions as well. The malabsorp- tion may be very mild and only detectable on biopsy. Therefore I suspect this neurological illness was secondary to coeliac disease, and that this Figure 4 Coronal section of the cerebral hemispheres at ataxia asso- the level of the pulvinar shows small areas of cavitation at patient had progressive myoclonic the greylwhite matterjunction, most evident in the region ciated with coeliac disease (Ramsay-Hunt syn- of the left parietal convexity. There are no signs of drome). haemorrhage or evidence of malignancy. Progressive ataxia, focal seizures, and malabsorption syndrome in a 41 year old woman 229 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from Figure 5 Sectionfrom the Immunostains for glial fibrillary acid protein, abnormal region ofthe left parietal convexity an astrocytic marker, confirmed gliosis at the photographed at low power grey-white matter interface. Immunostaining shows thefeatures for macrophages showed an accumulation of ofa necrotising leukoencephalopathy, with these cells in the white matter around blood cavitation in the subcortical vessels and areas of infarction could be seen. white matter. No sign of No granulomata were identified; the lympho- haemorrhage is present cytes around the blood vessels comprised a (haematoxylin and eosin). mixed population of B and T cells. Stains for amyloid, bacteria, fungi, and parasites were all negative. The deep grey matter structures, hypothala- mus, and cranial nerves were spared, but in the cerebellum there were numerous thick walled blood vessels with active vasculitis and a cavitating leucoencephalopathy. In the the vessels within the white matter were the most severely affected by the same patho- logical process, but there was also evidence of less severe grey matter involvement. In summary, the necropsy findings were a necrotising leucoencephalopathy with vasculi- tis, and gliosis involving astrocytes and microglia. The patient did have coeliac disease with splenic atrophy, and the incidental but very unusual finding of mesenteric lymph node cavitation. There was no convincing evi- This was more than just perivascular rarefac- dence of alcoholic liver damage. tion, and in places there was cavitation between the junction of the grey and white matter. In the cerebellum there were no exter- Conclusions nal lesions, but a similar discoloured appear- Dr NA Flecher's diagnosis: ance was noted in the white matter on cross * Ramsay-Hunt syndrome associated with section, with a brownish colour around some coeliac disease (progressive myoclonic ataxia) blood vessels suggesting previous haemor- Pathological diagnosis: rhage. There were similar findings in the * Necrotising leucoencephalopathy with vas- brainstem with discolouration around the culitis (associated with coeliac disease) blood vessels. * Mesenteric lymph node cavitation Low power histological view of the cere- * Coeliac disease brum (fig 5) showed good preservation of the * Acute bronchopneumonia cortical mantle, the main site of damage being the white matter, which was cavitated and had http://jnnp.bmj.com/ a sponge-like appearance; the adjacent blood Comment vessels were prominent and thick walled. On The histological features of the small bowel high power (fig 6) there were multiple areas of biopsies in this patient, along with the cavitation, and the blood vessels showed necropsy findings in the jejunum and ileum, perivascular haemorrhage in both the grey and confirm the diagnosis of coeliac disease. No white matter. These vessels had cuffs of evidence of Whipple's disease was noted and mononuclear cells, which infiltrated the white there was no evidence of lymphoma. The matter, and in several areas there was frank unusual findings in the mesenteric lymph on September 30, 2021 by guest. Protected copyright. vasculitis and surrounding infarction. nodes have previously been reported in coeliac disease.'3 The pathogenesis of this abnormality is unknown, and unlike other features of coeliac disease, the lymph node changes apparently do not respond to a gluten free diet. The presence of a necrotising leucoen- cephalopathy associated with vasculitis throughout the CNS has previously been reported in coeliac disease. 1012 The mecha- nism of this abnormality is unknown; patients with coeliac disease have been reported to have a wide range of immunological abnor- malities, and vasculitis has been described in the skin and in other sites in this disorder. Immune complex deposition has been sug- Figure 6 Abnormal subcortical white matter contains gested as the pathogenetic mechanism for the numerous thickened blood vessels which are infiltrated by vasculitis, but this remains unproved. The his- lymphocytes, macrophages, and occasional polymorphs. tological features of the CNS vasculitis did not No sign of recent haemorrhage is noted but there is extensive cavitation and gliosis in the adjacent white exhibit the features associated with granulo- matter (haematoxylin and eosin x 40). matous angiitis, amyloid angiopathy, sarcoido- 230 Mumford, Fletcher, Ironside, Warlow J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.2.225 on 1 February 1996. Downloaded from sis, Wegener's granulomatosis, giant cell were not included in the clinicopathological arteritis, or polyarteritis nodosa. The distribu- case conference presentation. tion of the vasculitic lesions in the CNS was 1 Schwartz MA, Selhorst JB, Ochs AL, et al. Oculomasti- more extensive at necropy than the clinical catory myoarrhythmia: a unique symptomatology had suggested, although the occurring in Whipple's disease. Ann Neurol 1986;20: 677-83. striking involvement of the brain stem, cere- 2 Marsden CD, Obeso JA. Viewpoints on the Ramsay Hunt bellum, subcortical white matter, and spinal syndrome: 1. The Ramsay Hunt syndrome is a useful clinical entity. Mov Dis 1989;4:6-12. cord correlates well with the major neurological 3 Marsden CD, Hallett M, Fahn S. The nosology and patho- abnormalities in this patient. physiology of myoclonus. In: Marsden CD, Fahn S, eds. Movement disorders. Butterworth Internationial Medical The association of coeliac disease and a Reviews. Vol 2. Neeurology. London: Butterworth progressive neurological disease of this nature Scientific, 1982:196-248. 4 Koskiniemi ML. Baltic myoclonus. Adv Nenr-ol 1986j43: is not unique. Presentation of adult coeliac 57-64. disease as an isolated cerebellar syndrome has 5 Iizuka R, Hirayama K, Maehara KA. Dentato-rubro- pallido-luysian atrophy: a clinico-pathological study. Y been reported,"4 and Kinney et all5 reviewed Neurol Neurosurg Psychiatry 1984;47: 1288-98. the cases of 10 patients with coeliac disease 6 Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T. Myoclonus epilepsy associated with ragged red fibres who exhibited a progressive CNS degenera- (mitochondrial abnormalities): disease entity or syn- tion. In a review of the diverse causes of the drome? Light- and electron-microscopic studies of two cases and review of the literature. . Nenrol Sci 1980;47: Ramsay-Hunt syndrome, which was defined 117-33. as the triad of severe myoclonus, progressive 7 Lu CS, Thompson PD, Quinn NP, Parkes JD, Marsden CD. Ramsay Hunt syndrome and coeliac disease: a new ataxia, and epilepsy with cognitive change, association? Mov Dis 1986;1:209-19. Marsden and Obeso2 identified two patients in 8 Berkovic SF, Andermann SF, Carpenter S, Wolfe LS. Progressive myoclonus : specific causes and a series of 10 who had coeliac disease and mal- diagnosis. NEngJMed 1986f315:296-305. absorption as part of the overall clinical pic- 9 Thomas PK, Abrams JD, Swallow D, Stewart G. Sialidosis type 1: cherry red spot-myoclonus syndrome with siali- ture. dase deficiency and altered electrophoretic mobility of some enzymes known to be glycoproteins. 7 Nenrol We are grateful to Dr R G Will for permission to report this Neurosurg Psychiatry 1979;42:873-80. case and to Dr R Gibson for assistance with the neuroradiolog- 10 Hankey GJ. Isolated angiitis/angiopathy of the nervous sys- ical investigations. tem. Cerebrovasc Dis 199 1;1:2-15. 11 Holdstock DJ, Oleesky S. Vasculitis in coeliac disease. BM.7 1970;4:369. Addendum 12 Rush PJ, Inman R, Bernstein M, Carlen P, Resch L. The case was presented in this form as a clini- Isolated vasculitis of the central nervous system in a patient with celiac disease. Ain Y Med 1986;81:1092-4. copathological conference at the Edinburgh 13 Holmes GKT. Mesenteric lymph node cavitation in coeliac Advanced Neurology Course, 30 March 1995. disease. Gut 1986f27:728-33. 14 Finelli PF, McEntee WJ, Ambler M, Kestenbaum D. Adult The patient had a cerebral biopsy per- celiac disease presenting as a cerebellar syndrome. formed before death and was treated inten- Neurology 1980;30:245-9. 15 Kinney HC, Burger PC, Hurwitz BJ, Hijmans JC, Grant sively with steroids and cyclophosphamide JP. Degeneration of the central nervous system associ- without clinical benefit. These clinical details ated with celiac disease. 7 Neuirol Sci 1982;53:9-22. http://jnnp.bmj.com/ on September 30, 2021 by guest. Protected copyright.