1140 Letters to the Editor J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.9.1140 on 1 September 1994. Downloaded from cerebellar connections with the brainstem, tude, as we show by the presentation of two especially the superior cerebellar peduncle, cases. should be spared for a postural type of Starting in 1981, case 1, a 28 year old tremor to occur. An intention tremor results woman, had repeatedly experienced paraes- if these connections are involved.4 The pos- thesias of the extremities and episodes of tural tremor caused by cerebellar lesions is a blurred vision. In 1988, during a further slow tremor of 4 to 5 Hz and is thought to bout of visual deterioration MRI of the result from hypotonia of the affected limbs.4 brain showed swelling and contrast The postural tremor in our case was enhancement of the optic chiasm and of the unexpected considering the location of the prechiasmatic portion of the optic nerves. mass in the thalamus with compression of An exploratory frontal craniotomy six the adjacent basal ganglia. The structures months later showed atrophic optic nerves likely to be affected by the cyst include the that were encased by abnormally thick basal ganglia and their connections, denta- arachnoidea but no tumour. torubrothalamic fibres, and the thalamic One year later the patient was first seen nuclei. Lesions of these structures are not at our department for rapid onset of left leg known to produce isolated postural weakness and bilaterally ascending hypaes- tremors. The mass in our patient could be thesia. At that time visual acuity was expected to produce a rest tremor. Even an reduced to finger counting. MRI showed intention tremor is conceivable considering swelling of the upper thoracic cord with the possible compression of the superior irregular intramedullary enhancement after cerebellar peduncle by the cyst. As men- giving gadolinium-DTPA. The brain tioned, only discrete lesions of the cerebel- seemed normal, including the chiasm. lar hemisphere have been considered to Lumbar puncture and a spinal angiogram cause postural tremors and our patient had were uninformative. Laboratory tests were neither hypotonia nor involvement of the negative for involvement of any other organ, cerebellar hemispheres. systemic infection, or collagen vascular dis- The tremor in our case was contralateral ease. No specific antibodies except for an to the side of the tumour and responded to intermittently raised titre against Toxo- aspiration of the cyst contents, suggesting plasma gondii was found. that the pressure exerted by the cyst on Over the next four years the patient con- adjacent neural structures was in some way tinued to have bouts of myelitis at times responsible for the production of the involving almost the entire spinal cord, as tremor. To the best of our knowledge there shown by MRI. Cell counts in the CSF has been no previous report of unilateral ranged from 0 to 10/mm3 and consisted postural tremor caused by a thalamic or mainly of lymphocytes and activated basal ganglia lesion. monocytes. Sometimes fat containing VEDANTAM RAJSHEKHAR macrophages indicating tissue necrosis were Department ofNeurological Sciences, Christian Medical College and Hospital, also seen. The protein content of CSF was Vellore 632004, India mostly increased and ranged from 71 to 153 mg/100 ml, but there was no evidence of 1 Friede RL, Yasargil MG. Supratentorial intrathecal immunoglobulin production. intracerebral epithelial (ependymal) cysts: for review, case reports and fine structure. Repeated search oligoclonal bands was Neurol Neurosurg Psychiatry 1977;40: negative. 127-37. Various therapeutic regimens including 2 de Yebenes GJ, Gervas JJ, Iglesias J, et al. high dose steroids, immunoglobulins, Biochemical findings in a case of parkinson- ism secondary to brain tumor. Ann Neurol immune adsorption, and antibiotic treat- 1981;11:3 13-6. ments failed to stabilise the patient's clinical T 1 weighted axial (A) and sagittal (B) MRI 3 Liversedge LA. Involuntary movements. In: condition. When she was last seen in mid- of the patient showing the hypointense cystic Vinken PJ, Bruyn GW, eds. Handbook of 1992 she was bedridden because of a lesion in the right thalamus and basal ganglia. clinical neurology, Vol 1. Amsterdam: North Compression of the upper midbrain by the mass Holland Publishing Co, 1969:277-92. spastic tetraparesis with a bilateral http://jnnp.bmj.com/ is evident in the sagittal scan. 4 Lang AE. Movement disorder symptomatol- sensory level at C2 and had unchanged ogy. In: Bradley WG, Daroff RB, Fenichel severe visual impairment. MRI of the brain GM, Marsden CD, eds. Neurology in clinical practice, Vol 1. Boston: Butterworths; continued to be normal whereas the spinal Heinemann, 1991:315-36. cord at the cervical and upper thoracic At follow up three months after surgery, region was very atrophic. The patient the patient was asymptomatic and had no refused the administration of contrast tremors of the left upper or lower limbs. A material at that time. small residual cyst was seen on CT but it For five months case 2, a 22 year old was not producing any mass effect or ven- woman, had experienced continuous deteri- on September 26, 2021 by guest. Protected copyright. tricular dilatation. No further treatment was oration of visual acuity associated with offered and she was advised clinical and CT MRI of neuromyelitis optica: evidence increasing bilateral leg weakness and uri- monitoring. for a distinct entity nary incontinence before she was seen at Intracranial tumours are on occasions our department. Visual field testing showed known to produce a parkinsonian syndrome Neuromyelitis optica was originally concentric narrowing on the right and a with rest tremors, bradykinesia, and described as a distinct demyelinating disor- temporal hemianopia on the left with spar- rigidity.23 Another type of tremor that has der characterised by visual disturbances and ing of the fovea. Her right arm distal to the been described in association with intra- spinal cord signs occurring closely in time.' elbow was mildly hypaesthetic and sensa- cranial masses is "rubral tremor". Involve- Later studies on patients presenting with tion to pinprick and pain was reduced dis- ment of the red nucleus and the decussating this syndrome often reported the subse- tally from T7 bilaterally. The plantar fibres of the superior cerebellar peduncle by quent evolution of additional neurological response was upgoing on both sides. A lesions in the midbrain region has been deficits,2 found pathological evidence for a spinal tap gave a colourless CSF with 4 implicated in the production of "rubral more widespread demyelination, or dis- lymphocytes/mm' and a protein concentra- tremor".4 In both these instances, the closed other specific aetiologies such as tion of 50 mg/100 ml. There was no evi- tremor is present at rest, although rubral acute disseminated encephalomyelitis, dence of oligoclonal bands. MRI showed tremors may be aggravated by maintenance Behcet's disease, or systemic lupus erythe- right sided enlargement of the chiasm and of a posture or goal directed movement. matosus.3 From these findings it was con- of the right optic nerve with uptake of con- Postural tremors can theoretically occur cluded by many that neuromyelitis optica trast material. The remainder of the brain in isolated cerebellar hemispheric lesions was inseparable from multiple sclerosis and was normal. There was also minimal including mass lesions, but this manifesta- its existence as a specific entity was ques- swelling of the cervical medulla and patchy, tion is rarely seen in clinical practice. The tioned.34 MRI promises to alter this atti- intramedullary enhancement from Cl to Letters to the Editor 1 141 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.9.1140 on 1 September 1994. Downloaded from

C4. Laboratory tests for specific causes of M myelitis were negative. The patient was I tf- given steroids but improvement was mini- mal. A repeat MRI two months later showed a further increase in chiasmal pathology with extension into both optic nerves (fig 1). Spinal cord involvement seemed almost unchanged (fig 2). After a waxing and wan- ing of symptoms for the next 18 months her last MRI confirmed still active optochias- matic and spinal cord disease which spared the remainder of the CNS. The MRI findings in both our patients exactly parallelled the pattern of damage described as characteristic for neuromyelitis optica in pathological studies.5 They con- sisted of swelling and congestion of the optochiasmatic region and the spinal cord due to severe demyelination which often progresses to whole tissue necrosis. Medullary inflammation extended over many segments, tended to involve both grey and white matter, and had a predilection for the cervical and upper thoracic cord. The brain itself remained free from demyelina- tion. This pattern was very different from the distribution of lesions found in multiple sclerosis. There MRI typically shows numerous round or oval signal hyper- intensities, which are scattered throughout the brain with a predilection for the periventricular region.6 Extensive spinal cord damage seen on MRI as in our patients has already been described in four other patients with sus- pected neuromyelitis optica.57 The MRI fol- low up of optic neuritis attributed to Figure 1 Case 2: Magnification of Tl weighted coronal cuts through the chiasm (left) and optic neuromyelitis optica has also been nerves (right) before (upper panel) and after (lower panel) application ofgadolinium-DTPA. There reported.8 Yet our study for the first time is pronounced asymmetric swelling of the chiasm with contrast enhancement extending into both optic presents the full diagnostic potential of MRI nerves (arrows). for this disorder-that is, to show disease activity in both optic chiasm and spinal cord of the same patient and to rule out other abnormalities in the brain. It is also impor- tant to stress that the disease of our patients remained limited strictly to the optic nerves, chiasm, and spinal cord during a relapsing- remitting course of at least seven and two years, respectively. We also found no evi-

dence for any other disorder previously http://jnnp.bmj.com/ associated with neuromyelitic optica such as acute disseminated encephalomyelitis and vasculitic or granulomatous diseases. In accord with more recent findings,' both our patients exhibited a clinical course of the disease rather different from earlier descrip- tions,4 and oligoclonal bands were not found in their CSF.

Our findings provide further evidence for on September 26, 2021 by guest. Protected copyright. the existence of Devic's Disease as a noso- logical entity and document the important contribution of MRI in separating it from a "syndrome" of associated symptoms due to other pathology.5 This notion will enable new research into the aetiology and treat- ment of this often devastating demyelinat- ing disorder. F FAZEKAS H OFFENBACHER R SCHMIDT Department ofNeurology and MR Institute S STRASSER-FUCHS Department ofNeurology, Karl-Franzens University, Graz, Austria Correspondence to: Dr Franz Fazekas, Depart- ment of Neurology, Karl-Franzens University, Auenbruggerplatz 22, A-8036 Graz, Austria. . ^ ' - - ____...;_____ 1 Devic E. Myelite subaigue compliquee de nevrite optique [abstract]. Bull Med (Paris) Figure 2 Case 2: Sagittal (upper panel) and axial (lower panel) contrast enhanced Tl weighted 1894;8:1033-4. MRI*~~-ofthe spine shows multiple irregular bright areas within the entire cervical cord. 1142 Letters to the Editor J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.9.1140 on 1 September 1994. Downloaded from 2 Shibasaki H, Kuroda Y, Kuroiwa Y. Clinical those described, in the subsequent years, showed complete recovery in the right visu- studies of multiple sclerosis in Japan: classi- cal multiple sclerosis and Devic's disease. which resolved either spontaneously or with al field. The left eye remained unchanged. J Neurol Sci 1974;23:215-22. short courses of steroids. Repeat DNA Three months later, while taking 6 mg 3 Adams RD, Victor M. Principles of neurology, binding assays confirmed high titres. prednisolone once daily and with an rNR 3rd ed. New York: McGraw-Hill Inc, 1985: Examination of the CSF during acute reduced to 19, she had a recurrence of 706-7. 4 Kuroiwa Y. Neuromyelitis optica (Devic's dis- episodes of her neurological illness revealed vision loss in her right eye, which once ease, Devic's syndrome). In: Koetsier JC, no lymphocytes with IgG bands at y 1 and 2 again responded to pulsed methylpred- ed. Demyelinating diseases. Vinken PJ, Bruyn (atypical for multiple sclerosis). In 1987 she nisolone and increased anticoagulation GW, Klawans HL, eds. Handbook ofClinical Neurology, Vol 47. Amsterdam: Elsevier, was found to have moderately raised anti- (INR > 3 0). On recovery, her visual acuity 1985:397-408. (Rev series 3.) cardiolipin antibodies and low levels of C3 was 6/9 but there was a persistent right alti- 5 Mandler RN, Davis LE, Jeffery DR, Kornfeld and C4. In 1991 another positive anticardi- tudinal field defect. She has subsequently M. Devic's neuromyelitis optica: a clinico- olipin IgG level of 8 lGpl units was record- found her vision to be extremely sensitive to pathological study of 8 patients. Ann Neurol 1993;34:162-8. ed (normal < 5). Urinary incontinence anticoagulation and steroid treatment, sta- 6 Fazekas F, Offenbacher H, Fuchs S, et al. developed, necessitating insertion of a tho- bilising at 10 mg prednisolone once daily Criteria for an increased specificity of MRI racic epidural stimulator in 1989. At 27 and an INR of 3 0, with preservation of interpretation in elderly subjects with sus- ill- pected multiple sclerosis. Neurology 1988; years she had her first ophthalmological visual acuity and field. 38:1822-5. ness. Over a period of 24 hours she devel- The differential diagnosis of this patient's 7 Tashiro K, Ito K, Maruo Y, et al. MR imaging oped painless loss of vision in her left eye, illness includes multiple sclerosis and the of spinal cord in Devic's disease. Jf Comput which she described as a gradual "keyhole" syndrome of lupus anticoagulant. Lupus Assist Tomogr 1987;11:516-7. 8 Barkhof F, Scheltens Ph, Valk J, Waalewijn C, constriction of her visual field. There was anticoagulant can give rise to neurological Uitdehaag BMJ, Polman CH. Serial quanti- no associated headache or diplopia but disease and in such cases may be associated tative MR assessment of optic neuritis in slight pain on left ocular movement. She with systemic lupus erythematosus,' as in a case of neuromyelitis optica, using Gadolinium-"enhanced" STIR imaging. was diagnosed as having an acute optic neu- our patient. Systemic lupus erythematosus Neuroradiology 1991;33:70-1. ritis, but despite treatment with oral and only very rarely produces identical symp- pulsed dose steroids her visual acuity toms to typical demyelinating optic decreased to no perception of light over a neuritis.23 The pattern of visual loss in both four day period and failed to improve. of our patient's eyes was atypical for prima- Examination in May 1992 revealed visual ry demyelinating optic neuritis; in her left acuities of 6/24 corrected and N14 in the eye, she had the uncharacteristic features of right eye and no perception of light in the severe vision loss with failure to improve Ischaemic optic neuropathy, transverse left. Her colour vision was reduced to 10/17 and later pronounced retinal vascular atten- myelitis, and epilepsy in an anti- correct Ishihara plates. She had a dense left uation, and in the right eye no associated phospholipid positive patient with afferent pupillary defect with a pale atrophic pain on ocular movement, no CSF lympho- systemic lupus erythematosus left optic disc and attenuated retinal vessels. cytes, and progressive visual loss to no per- The right optic disc was normal. Goldman ception of light over 18 days despite We report a 37 year old woman who had perimetry showed a right inferior altitudinal substantial treatment with immunosuppres- severe, bilateral visual loss in association field defect. Neurological examination sants, more suggestive of an ischaemic optic with transverse myelitis, epilepsy, serolo- showed bilateral extensor plantars, residual neuropathy. Her subsequent response and gical evidence of systemic lupus erythe- weakness, and spasticity of both lower limbs sensitivity to anticoagulation and steroids, matosus, and the presence of anti and reduced vibratory sense below the level we believe, favour a vascular underlying phospholipid antibodies. Recognition of a of the anterior iliac spine. She had two pathology, most likely ischaemia of the possible underlying thrombotic aetiology periungual splinter haemorrhages and was microvasculature of the optic nerve in rela- suggests that long term anticoagulation and normotensive. Investigations included anti- tion to antiphospholipid antibodies, and not immunosuppressive treatment could pre- nuclear antibody (ANA) 1/10, negative primary demyelination. vent progression and relapses of neurologi- DNA antibody tests, normal immune com- Transverse myelitis and epileptiform cal and ophthalmic complications in plex levels, reduced C4 concentrations to seizures are known to occur in the presence patients with antiphospholipid related dis- 0 07 g/l (normal 0 2-0 5), absence of CSF of antiphospholipid antibodies.45 ease. lymphocytes, a platelet count of 167, a neg- Ophthalmic vaso-occlusive phenomena The 37 year old housewife was admitted ative venereal disease research laboratory associated with high levels of phospholipid in May 1992 with a three day history of test (VDRL), and normal CT brain and antibodies include anterior ischaemic optic

visual loss in her right eye, preceded by a orbit scans. MRI was contraindicated due neuropathy, branch and central retinal http://jnnp.bmj.com/ severe frontal headache lasting 24 hours. to the presence of the thoracic epidural artery occlusions, amaurosis fugax, and There were no associated symptoms of implant. Treatment with three daily intra- venous occlusions.67 Splinter haemorrhages retro-orbital tenderness or pain on eye venous pulses of methylprednisolone (500 have previously been reported to occur with movement. mg) with oral aspirin (75 mg daily), was ocular vasooclusive disease in the antiphos- She had a complex history. Aged 13 started on admission with no initial visual pholipid syndrome.8 Oppenheimer and months she had had febrile convulsions and improvement. On day five she was given an Hoffbrand in 1986, were the first to at 11 years of age developed epilepsy. At 16 intravenous pulse of cyclophosphamide describe the association of spinal myelopa- years of age she was mildly hypertensive (250 mg) but by day 11 the visual acuity thy and optic neuritis in a case similar to and developed recurrent attacks of was reduced to hand movements. Further ours.9 In the same paper, they reviewed 13 on September 26, 2021 by guest. Protected copyright. angioneurotic oedema, Raynaud's phenom- results showed a strongly positive anticardi- previously reported cases of patients with enon, and photosensitive skin rashes. At the olipin IgG level of 33-6Gpl units, negative known systemic lupus erythematosus and age of 22 she was admitted with diminished IgM antibodies, and a positive lupus antico- optic neuritis: six had at some point had a power in her right leg, bilateral extensor agulant. A diagnosis of an ischaemic optic spinal myelopathy and they suggested that plantars, and a sensory loss at T2. She neuropathy related to systemic lupus ery- disease in the optic nerve and spinal cord improved spontaneously but relapsed a thematosus was made. She was given a fur- might have a common underlying aetiology. month later with weakness in her left arm ther pulse of intravenous cyclophosphamide Recently, a possible mechanism for cere- and leg, bilateral extensor plantars, and a (500 mg) and anticoagulated with heparin brovascular diseases in patients with stroke sensory level below T9 on the right and and warfarin. On day 18 her vision was and antiphospholipid antibodies was report- between C4 and T2 on the left. All investi- reduced bilaterally to no perception of light ed with affected patients having human gations including a myelogram were normal and she was registered blind. She was given brain microvascular endothelial reactive apart from a raised erythrocyte sedimenta- two daily pulse doses of methylprednisolone antibodies present.'0 tion rate (55 mm/hour), antinuclear anti- (2 g) with no immediate effect. On day 25 The association of antiphospholipid anti- body titre borderline at 1/40, DNA binding she showed an improved visual acuity on bodies with transverse myelopathy, epilep- significantly raised at 61%, and a positive the right of hand movements and was dis- sy, and optic neuropathy may be part of the lupus erythematosus test. A diagnosis of charged fully anticoagulated (INR 3 0) and spectrum of antiphospholipid disease. This probable systemic lupus erythematosus with on oral prednisolone (10 mg once daily) has important therapeutic implications in transverse myelitis was made. Her neuro- and aspirin (75 mg once daily). that long term anticoagulation, reducing the logical deficits improved spontaneously with Three weeks later the right visual acuity incidence of vascular thromboses, possibly residual weakness on the left. She had had improved to 6/9, N5 and 16/17 Ishihara with immunosuppression, may prevent neu- recurrent episodes of myelopathy, similar to colour plates unaided. Goldman perimetry rological and neurophthalmic relapses in