Journal ofNeurology, , and 199 1;54:499-502 499

Neurosarcoidosis-demonstration of meningeal J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.6.499 on 1 June 1991. Downloaded from disease by gadolinium enhanced magnetic resonance imaging

K T Khaw, H Manji, J Britton, F Schon

Abstract (attributed to bilateral mastoidectomies) and Arriving at a firm diagnosis of neuro- left sided ninth to twelfth lower cranial nerve continues to pose serious palsies. examination was problems, particularly when evidence of unremarkable as was myelography and ver- granulomatous disease outside the tebral angiography. taken of a nervous system is lacking. The common- possible mass in the left nasopharynx revealed est mode of presentation of neuro- no definite abnormality. Her erythrocyte sarcoidosis is with cranial nerve palsies. sedimentation rate was 40 mm/hr. Her Two cases of presumed neurosarcoidosis neurological condition again spontaneously with cranial nerve palsies showed clear improved. She remained well until the age of evidence of focal meningeal disease on 61 when a 5 x 7 cm mass was removed from gadolinium-DTPA enhanced MRI brain the left buttock which on histological examin- scans. Although not specific for sar- ation was consistent with . coidosis, this technique may be very The patient then developed vaginal bleeding useful in aiding the diagnosis in sus- and other persistent gynaecological symp- pected cases. toms. These were treated surgically with hys- terectomy and bilateral salpingo-oophorec- Sarcoidosis is a disseminated disease of un- tomy at the age of 63 and colpectomy at the known aetiology characterised by non-caseat- age of 64. Histology from both these ing granulomatous infiltration. Neurological procedures revealed sterile non-caseating symptoms occur in about 5% of patients granulomatous tissue. The patient continued known to have the disease'2 and in up to 14% to have persistent vaginal ulceration and of patients at necropsy.' The commonest developed a urethro-vaginal fistula with mode of presentation of neurosarcoidosis is granulomatous pathology. with cranial nerve palsies.' Although facial At the age of 66 she had six episodes of nerve involvement, in particular, is frequently dysarthria, blurred vision with scintillating encountered, the pathophysiology of these teichopsia and numbness in her lasting lesions is poorly understood, probably for about 30 minutes, without subsequent because they are associated with a good prog- or vomiting. Neurological examina- nosis. tion was unremarkable apart from severe http://jnnp.bmj.com/ Major diagnostic difficulties can arise, bilateral deafness and a diminished left-sided particularly in patients with no evidence of gag reflex. The diagnosis was felt to be granulomatous disease outside the nervous vertebrobasilar transient ischaemic attacks. system, because of problems in obtaining Investigations revealed an ESR of 46 with suitable tissue for histological examination. Diffuse meningeal infiltration particularly in at the skull base region is frequently found on September 27, 2021 by guest. Protected copyright. necropsy4 ' but is infrequently diagnosed positively during life, partly because until now imaging techniques have usually not shown up such meningeal involvement. This paper describes two patients with presumed neurosarcoidosis which with cranial Atkinson Morley's presented Hospital, London, UK nerve palsies, in whom evidence of focal Department of meningeal disease was demonstrated on Neuroradiology gadolinium-DTPA (Gd-DTPA) enhanced K T Khaw J Britton MRI. Department of Case 1 H Manji A 65 year old white woman presented at the F Schon age of 39 with right sided pleuritic chest pain Correspondence to: Dr Schon, Department of and an abnormal showing an Neurology, Atkinson irregular mass in the right apex. Despite Morley's Hospital, Copse Hill, Wimbledon, London extensive investigations no firm diagnosis was SW20 ONE, UK made and her condition spontaneously Received 3 April 1990 improved. At the age of 43 she developed and in revised form Figure 1 Case 1. Enhanced axial CT scan through 12 October 1990. , and dysphonia. She was posteriorfossa showing enhancement of the tentorium Accepted 7 November 1990 found to have bilateral conductive deafness cerebelli on the left. 500 Khaw, Manji, Britton, Schon

elevated serum calcium of 2 79 mmol/l. A Case 2 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.6.499 on 1 June 1991. Downloaded from chest radiograph showed a small calcified A 53 year old businessman who had been born lesion in the left lower zone only. Serum in India but had lived in England for twenty angiotensin converting enzyme was normal. years developed double vision in 1985, which CT scan showed mild asymmetrical dilatation on examination was due to a partial pupil of the lateral ventricles and a possible mass in sparing right sided third nerve palsy. Extensive the left posterior fossa with contrast investigations were all unremarkable including enhancement of the tentorium cerebelli on the erythrocyte sedimentation rate, chest left (fig 1). An MRI scan was obtained using a radiograph and enhanced CT brain scan. Siemens Magnetom 15 Tesla scanner. A T2 Although no definite diagnosis was made at weighted sequence (TR 3-2 s TE 90 ms) that time, the patient was treated with a short showed no evidence of a mass lesion (fig 2a) course of oral (40 mg for two but confirmed mild asymmetrical hydro- weeks) and all his symptoms and signs fully cephalus and demonstrated a Chiari malfor- resolved. mation. In addition abnormal bright He remained well till June 1989 when he enhancement of the meninges of the left again complained of double vision, which on cerebral hemisphere, tentorium cerebelli and this occasion was due to a complete right-sided left side of the posterior fossa was shown on lateral rectus palsy. Whilst he was being inves- Gd-DTPA enhanced Ti weighted sequences tigated for this isolated cranial nerve palsy, he (TR 0 5 s TE 17 ms) carried out in the gradually developed right facial numbness, coronal and axial planes (fig 2b, c). Unenhan- increasing hoarseness of his voice and ced Ti weighted images were not obtained as dysphagia over a six week period. Examination a bright sequence from the meninges would revealed multiple right-sided cranial nerve indicate a fairly acute bleed which was clin- palsies involving the fifth, sixth, ninth and tenth ically highly unlikely. nerves. At the age of 67 she developed epilepsy with Investigations revealed an ESR of 55 mm/hr eight attacks of right sided jerking followed by but normal serum calcium and angiotensin loss of consciousness for up to 20 minutes. converting enzyme levels. Repeat chest These attacks stopped after treatment with radiograph and CT brain scans were again phenytoin was started. The EEG was un- normal. Cerebrospinal fluid examination remarkable. The Mantoux test was negative at showed only mild abnormalities-six 1:10,000 dilution, was negative. , protein 0-84 g/l and glucose 4 1 No repeat CSF examination was carried out. mmol/l. Acid-fast bacilli were not seen or This woman had histologically proven non- cultured from the spinal fluid and cytological caseating granulomatous disease of the female examination confirmed the absence of malig- genital tract and of a subcutaneous buttock nant cells. The Mantoux test was clearly mass. Sarcoidosis affecting the uterus is well positive at a dilution of 1:10,000. A Kveim test recognised but in fact few proven cases have was not carried out. Gallium scanning showed been reported.' In addition she had evidence marked bilateral lacrimal gland and bilateral of neurological involvement, having had an hilar lymph node uptake, a pattern well recog- episode of cranial nerve palsies and epilepsy, nised in sarcoidosis.7 MRI scan with Gd- the latter being reported in up to 35% of cases DTPA enhancement showed clearcut abnor- http://jnnp.bmj.com/ of granulomatous .6 mal enhancement affecting only the meninges on September 27, 2021 by guest. Protected copyright.

Figure 2 Case 1. a) T2 weighted (TR 3-2 s TE 90 ms) axial magnetic resonance images obtained at the level of the pons showing no mass lesion or area of abnormal signal. The CSF returns a normal high signal on this sequence. b) axial and c) coronal Gadolinium-DTPA enhanced Ti (TR 0 5 s TE 17 ms) weighted MRI scans showing bright meningeal enhancement over 1'ft hemisphere and tentorium cerebelli. Neurosarcoidosis-demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging 501 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.6.499 on 1 June 1991. Downloaded from

Figure 3 Case 2. a) Axial and b) and c) coronal Gd-DTPA enhanced Tl weighted MRI scans showing enhancement of the tentorium cerebelli on the right. d) and e) Axial T2 weighted MRI scans again showing no abnormality in the brain stem or CSF.

on the right side maximal in the region of the scan, the lymphocytic CSF and the lack of any tentorium cerebelli (fig 3a, b, c). T2 weighted evidence over many years of follow up of other sequences using the same sequences as before major causes of meningeal disease such as showed no abnormality in the brain stem or carcinoma and . http://jnnp.bmj.com/ adjacent CSF (figs 3d, e). In sarcoidosis of the , This patient presented with two episodes of leptomeningeal disease is the commonest cranial nerve palsies without any clinical pattern of involvement seen, and may be local- evidence of systemic disease outside the central ised or widespread, resulting in focal or dis- nervous system. The illness was felt to be due seminated meningeal nodules or plaques.2 This to sarcoidosis although tuberculosis was may result in basal obstruction of ventricular

obviously an important differential diagnosis. outflow with , and cranial nerve on September 27, 2021 by guest. Protected copyright. The patient was again treated with oral palsies. Less commonly, granulomatous steroids, initially dexamethasone (16 mg/day masses can be found within the cerebral paren- for three weeks) and subsequently put on to a chyma, or there may be infiltration of the reducing regime of prednisolone over a six vascular structures.8'0 month period. He was also treated with CT features of neurosarcoidosis are well isoniazid (600 mg/day for six months) as a documented,'13 with hydrocephalus reported single agent as prophylaxis against activating as the most common CT abnormality. any previous tuberculosis. There was a gradual Granulomatous masses within the cerebral but steady improvement over a three month parenchyma may be isodense or hypodense on period, during which all his cranial nerve CT and usually enhance with contrast. Menin- palsies resolved. geal nodules or plaques are shown by focal or diffuse thickening and contrast enhancement on Discussion CT; these appearances cannot be distinguished Both these cases presented with multiple lower from bacterial or malignant infiltration. cranial nerve palsies. In the first case, the The MRI appearances of neurosarcoidosis patient was known to have non-caseating are less well documented. Intracerebral cortical granulomatous tissue affecting other organs. In or subependymal lesions may be shown on the second case, the evidence that the menin- MRI as regions of high signal on T2 weighted geal disease was due to sarcoidosis was based on images which enhance with Gd-DTPA.':415 the overall clinical picture and response to There are few reports of the demonstration of steroid treatment, combined with the gallium meningeal sarcoid infiltration with MRI. Greco 502 Khaw, Manji, Britton, Schon

and Steiner in 198716 reported high signal cement may well prove useful in monitoring J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.6.499 on 1 June 1991. Downloaded from intensity of the basal meninges in one of four the progress of the disease and in assessing the patients with neurosarcoidosis but Gd-DTPA effects of treatment. was not given. Normal meninges may occasion- ally show faint enhancement on administration of Gd-DTPA, but abnormally brightly enhan- cing meninges usually indicate meningeal 1 Scadding JG, Mitchell DN. Sarcoidosis. 2nd ed. London: Chapman and Hall, 1985. disease in conditions including inflammatory 2 Delaney P. Neurologic manifestations in sarcoidosis. Ann and malignant infiltration.17-19 As in CT scan- Intern Med 1977;87:336-45. 3 Ricker W, Clark M. Sarcoidosis: a clinico-pathologic review ning the appearances are non-specific and may of 300 cases including 22 autopsies. Am J Clin Pathol be due to a wide range of pathology. In both 1949;19:725-49. 4 Waxman JS, Sher JH. The spectrum of central nervous these patients no significant meningeal abnor- system sarcoidosis: a clinical and pathological study. Mt mality was noted on unenhanced MRI scans, Sinai J Med (NY) 1978;46:309-17. 5 Colover J. Sarcoidosis with involvement of the nervous but the meningeal enhancement seen in both system. Brain 1948;71:451-75. patients was of very high signal intensity, 6 Meyer JS, Foley JM, Campagna-Pinto D. Granulomatous angiitis ofmeninges in sarcoidosis. Arch NeurolPsychiatry strictly unilateral and on the same side as the (Chicago) 1953;69:587-600. cranial nerve palsies. 7 Bekerman C, Szidon JP, Pinsky S. The role ofGallium-67 in the clinical evaluation of sarcoidosis. Semin Roentgenol Gadolinium-DTPA is a paramagnetic con- 1985;XX(4):400-9. trast agent used in MRI which functions by 8 Kendall BE, Tatler GLV. Radiological findings in neurosar- coid. Br JRadiol 1978;51:81-92. altering local magnetic environments to change 9 Kumpe DA, Rao CVGK, Garcia JH. Intracranial neurosar- signal intensity in tissues where it accumulates. coidosis. J Comput Assist Tomogr 1979;2:324-30. 10 Leeds NE, Zimmerman RD, Elkin CM, Nussbaum M, Like radiographic contrast agents, it uniformly LeVan AM. Neurosarcoid of the brain and meninges. distributes throughout the extracellular space Semtn Roentgenol 1985;XX(4):387-92. 11 Hayes WS, Sherman JL, Stern BL. MR and CT evaluation and does not cross intact cell membranes or the of intracranial sarcoidosis. AJR 1987;149:1043-9. intact blood-brain barrier to any extent. 12 Ketonen L, Oksanen V, Kuuliala I, Somer H. Hypodense lesions in CT ofneurosarcoidosis. J Comput Administration of Gd-DTPA therefore high- Assist Tomogr 1979;2:324-30. lights damaged or altered tissue in a non- 13 Brooks BS, El-Gammal T, Hungerford GD, Acker J, Trevor RP, Russell W. Radiologic evaluation ofneurosar- specific manner, similar to radiographic con- coidosis: role of CT. AJNR 1982;3:513-21. trast administered in CT scanning. 14 Ketonen L, Oksanen V, Kuuliala I. Preliminary experience of magnetic resonance imaging in neuro-sarcoidosis. In one of these patients CT scan and un- Neuroradiology 1987;29:127-9. enhanced MRI scan failed to demonstrate 15 Miller DH. Magnetic resonance imaging in central nervous system sarcoid. Neurology 1988;38(3):378-83. significant intracranial pathology. The sen- 16 Greco A, Steiner RE. Magnetic resonance imaging in sitivity of MRI for detection of intracranial neurosarcoidosis. Magnetic Resonance Imaging 1987;5: 15-21. disease is superior to that of CT with a similar 17 Schorner W, Henkes H, Sander B, Felix R. MR imaging of specificity. This is further increased by the meninges: normal and pathological findings. Fortschr Rontgenstr 1988;149(4):361-8 (Eng Abstr). administration of Gd-DTPA. Gd-DTPA 18 Kilgore DP, Breger RK, Daniels DL, Pojunas KW, enhanced MRI should be performed in Williams AL, Haughton VM. Cranial tissues: appearances after intravenous injection Gd-DTPA. Radiology patients with suspected neurosarcoidosis as 1986;16:757-61. well as unsuspected cranial nerve palsies. 19 Davis PC, Friedman NC, Fry SM, Malko JA, Hoffman JC, Braun IF. Leptomeningeal metastasis: MR imaging. Changes in the extent and pattern of enhan- Radiology 1987;163:449-54. http://jnnp.bmj.com/ on September 27, 2021 by guest. Protected copyright.