J7ournal of Neurology, Neurosurgery, and Psychiatry 1993;56:201-203 201 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.2.201 on 1 February 1993. Downloaded from SHORT REPORT Brainstem encephalitis and the Miller Fisher syndrome

R KH Petty, R Duncan, G A Jamal, D Hadley, P G E Kennedy

Abstract uncular area on either side of the fourth A case is described ofa man with an acute ventricle, the right side being larger and longer. onset areflexic ataxic syndrome with par- These lesions were hyperintense on T2 weigh- tial ophthalmoparesis and normal limb ted and hypointense on T, weighted images. muscle power. There was evidence ofboth After intravenous injection of Dimeglumine a peripheral neuropathy and a brainstem gadopentetate both lesions showed T, encephalitis. The patient made a full shortening, confirming blood-brain barrier recovery and the interrelationship and breakdown. Neurophysiological studies dem- nosology of brainstem encephalitis and onstrated normal peripheral motor nerve con- the Miller Fisher syndrome are dis- duction and sensory potentials. F waves were cussed. absent in both peroneal and right median nerves (table). H waves were absent in both (7 Neurol Neurosurg Psychiatry 1993;56:201-203) tibial nerves. EMG of proximal and distal lower limb muscles showed no evidence of denervation. The possible relationship between the Miller He developed bilateral facial weakness, Fisher (MFS) and Guillain-Barre syndromes severe limb ataxia, dysequilibrium and total (GBS) has been the subject of much debate. `- areflexia, although he remained alert. He Some authors have regarded MFS as a variant improved after treatment with high dose of GBS4 while others have felt the MFS methylprednisolone and plasma exchange. involves the brainstem and bears similarities to Neurophysiological studies two weeks after the brainstem encephalitis of Bickerstaff presentation showed normal motor and sen- (BBE).5 We report a patient in whom the sory velocities, and an F wave now detectable clinical features and investigations were con- on stimulation of the right median nerve. sistent with both an acute cranial and limb Electromyography showed evidence of dener- polyneuropathy and brainstem encephalitis vation in the right masseter and orbicularis and discuss the nosology of BBE and MFS. oculi muscles. Two weeks after plasma http://jnnp.bmj.com/ Case report A 32 year old man with no past medical or family history, and no history of alcohol abuse was admitted with a four day history of occipital headache and subsequent numbness of the right cheek, nausea and vomiting, diplopia and unsteadiness. Examination revealed phasic nystagmus on right and left on September 26, 2021 by guest. Protected copyright. gaze, impaired pinprick sensation in the dis- tribution ofthe right trigeminal nerve and right limb ataxia. Reflexes were intact. CSF con- tained 229 white cells Ml (90% lymphocytes, 10% polymorphonuclear cells), and protein of 0-32 G/l. The next day he developed slurred dysarthria, hoarseness and nasal regurgitation. Institute of abducens Neurological Science, He had a partial right palsy, with Southern General phasic nystagmus on lateral and upgaze. There Hospital, Glasgow, UK was sensory loss in trigeminal territory on the R KH Petty with lower motor neuron facial R Duncan right, right G A Jamal weakness and right palatal palsy. He had D Hadley normal limb power and tone but reflexes were P G E Kennedy absent, except for the right biceps and bra- Correspondence to: chioradialis. There was mild symmetrical limb Dr Jamal ataxia and dysequilibrium so that he required Received 26 September to walk. Sensation was normal. Figure Cranial MRI, T2 weighted (SE 2000180) axial 1991 assistance section showing areas of hyperintensity in the posterolateral and in revised form Cranial CT was normal. MRI showed 15 May 1992 (fig) brain stem peduncular areas, on both sides of the fourth Accepted 26 May 1992 lesions in the posterolateral brainstem ped- ventricle 202 Petty, Duncan, _Jamal, Hadley, Kennedy

Table Neurophysiological studies during recovery although they did show fea- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.2.201 on 1 February 1993. Downloaded from Day of study tures of a brainstem disorder and MRI changes similar to our case. We are not aware ofrecently Day 5 Day 13 Day 139 described cases fulfilling all the diagnostic Common Peroneal criteria laid down by Bickerstaff. Motor velocity, m/sec 50 53 53 Amplitude mV 14-4 12 4 7 In 1956 Miller Fisher' described three cases Latency ms 3-7 4-1 3-2 which he regarded as variants of "acute idio- F wave latency ms ND ND 54 Median pathic polyneuritis". All patients had internal Velocity, m/s 61 52 and external ophthalmoplegic, ataxia and are- Amplitude mV 7-3 7-8 flexia. Late neuropsychological features were Latency ms 4 0 3-8 - F wave latency ms ND 30 32 absent. CSF protein was elevated in one Sural nerve patient. He proposed that these cases were Amplitude ,uV 11 9 3 9-8 Latency ms 2 2 3-3 3-8 variants of GBS, citing cases of GBS with cranial nerve involvement including internal ND = not detected. and external ophthalmoplegia. The symmetry of the ophthalmoparesis and the simulation of paralyses of conjugate gaze was unusual for a exchange he was able to walk unaided, with a purely peripheral lesion. There is supportive partial right abducens weakness, horizontal evidence that the ataxia could result from nystagmus on right lateral gaze and persisting mismatch of input of joint receptors and facial weakness. His speech had improved, he proprioception to the CNS.478 had recovered his limb reflexes and had only Thus there is a body of opinion that con- minimal limb ataxia. Normal or negative inves- siders the MFS as purely a peripheral cranial tigations during the acute illness included polyneuropathy, yet in at least some patients in EEG, visual evoked responses, chest radio- whom MRI was performed central involve- graph, full blood count, ESR, serum electro- ment was documented.9 1O Similarly, detailed lytes, syphilis serology, autoantibody screen, neurophysiological studies have not been car- serology for borrelia, legionella, toxoplasma, ried out in cases labelled as brainstem ence- HIV-I, brucella, hepatitis B, Epstein-Barr phalitis. virus, mycoplasma, urinary porphyrin screen, The interest in our case lies in its similarities and serum electrophoretic strip. to both these entities, and the implications for Six months later he had mild residual facial pathogenesis. There appears to be little doubt weakness, normal reflexes and no limb or gait that our patient had an acute inflammatory ataxia. MRI showed resolution of the previous brainstem disorder; MRI was abnormal and abnormalities, and F waves were now detect- showed recovery, and clinical features were able on stimulation of both peroneal and consistent with this. In addition, there were median nerves. features of peripheral nerve disease; areflexia with recovery, although this has been reported in brainstem disease," nerve conduction stud- Discussion ies showed initially absent and subsequently This patient suffered a monophasic illness with recovering F waves; although velocities virtually complete recovery. Diagnoses of both remained normal and the cause of the absent F MFS and BBE were considered but clinical waves could not be localised. This case clearly http://jnnp.bmj.com/ and laboratory features suggested both cannot be accepted as MFS; there was only intrinsic brainstem and peripheral nerve partial ophthalmoparesis, the CSF showed a disease, contrary to definitions of both these prominent lymphocytosis, and the MRI disorders. showed clear central involvement. Bickerstaff2 reported eight cases of "brain- There have been two previous reports of stem encephalitis". All presented with drowsi- MRI abnormalities in cases resembling our ness and a bulbar paresis including own.9 1o Taphoorn9 described CT and MRI

ophthalmoparesis. Of these eight, six devel- abnormalities within the brainstem in a patient on September 26, 2021 by guest. Protected copyright. oped deafness, six were ataxic, five had with features of both GBS and the MFS. depressed or absent reflexes and three extensor Neurophysiological investigations were con- plantars. During recovery six showed undue sistent with a demyelinating neuropathy. The lability of emotions and three showed Parkin- patient apparently improved but no neurophy- sonian features. Six patients had a CSF pleocy- siological or MRI follow up was reported. tosis. These cases were notable for recovery Giroud et al'0 reported a similar patient with despite severe neurological deficit, the severe an areflexic ataxic syndrome whose MRI cranial nerve dysfunction without respiratory showed an area of high T2 signal in the pons. or cardiovascular disturbance and the neuro- As in the previous case no follow up scan was psychiatric and extrapyramidal features occur- reported. ring during recovery.' This case exemplifies the problems with Subsequent cases described as BBE have not definition of both the MFS and BBE. It is fulfilled these criteria. Al-Din et al5 included possible that further MRI of patients with cases with a cranial polyneuropathy and ataxia clinical features similar to the MFS may reveal with areflexia and an elevated CSF protein (for other patients with evident central involvement example, their cases 3, 5, 13, 15, 16, 18). None and that full neurophysiological investigation showed late psychiatric or extrapyramidal fea- of patients with brainstem encephalitis of tures. The cases reported as BBE by Yaqub et whatever cause may identify a proportion of al6 did not show neuropsychiatric features patients with peripheral involvement. In view Brainsteni encephalitis and the Miller-Fisher syndronie 203 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.2.201 on 1 February 1993. Downloaded from 5 Al-Din AN, Anderson M, Bickerstaff ER, Harvey I. of the well recognised lack of other brainstem Brainstem encephalitis and the syndrome of Miller features in these cases, this peripheral involve- Fishers. A clinical study. Brain 1982;105:481-95. ment may even 6 Yaqub BA, Al-Deeb SM, Daif AK, et al. Bickerstaff be the dominant lesion. brainstem encephalitis. A grave non-demyelinating dis- ease with a benign prognosis. Jf Neurological Sciences 1990;96:29-40. 7 Ropper AH, Shahani B. Proposed mechanism of ataxia in 1 Miller Fisher. An unusual variant of acute idopathic Fisher's syndrome. Arch Neurol 1983;40:537-8. polyneurities (syndrome of opthalmoplegia, ataxia and 8 Jamal GA, Donaghy M. A peripheral mechanism for the areflexia). New Engl _J Med 1956;255:57-65. ataxia associated with the Miller Fisher syndrome of acute 2 Bickerstaff ER. Brainstem encephalitis. Further observa- ophthalmoplegia, ataxia and areflexia (Abstr). _7 Neurol tions on a grave syndrome with a benign prognosis. BMJ Neurosurg Psychiatry 1989;52:1210. 1957;i:1 384-7. 9 Taphoorn MJB, Lanting P, Hazenberg GJ, Uitdehaag BJM, 3 Bickerstaff ER. Brainstem encephalitis (Bickerstaff's ence- Kaiser MC. Observations on the lesion site in the Miller phalitis). In: Vinken PJ, Bruyn GW, eds. Handbook of Fisher syndrome: presentation of a case including CT and clinical neurology, vol 34. Amsterdam, North Holland, MRI. Acta Neurol Scand 1989;80:167-9. 1978:605-9. 10 Giroud M, Mousson C, Chapolin JM, Rifle G, Dumas R. 4 Jamal GA, Ballantyne JP. The localisation of the lesion in Miller Fisher syndrome and pontine abnormalities on patients with acute ophthalmoplegia, ataxia and areflexia MRI: a case report. I Neurol 1990;237:489-90. (Miller Fisher syndrome). A serial multimodal neu- 11 Asbury AK, McKhann GM, McDonald WI. Diseases of the rophysiological study. Brain 1988;111:95-114. nervous system. London: Heinemann 1986:355-6. http://jnnp.bmj.com/ on September 26, 2021 by guest. Protected copyright.