European Journal of Radiology 37 (2001) 5 – 7 www.elsevier.nl/locate/ejrad
Case report
Primary multifocal leptomeningeal gliomatosis Edmund Yik Kong Tsui a, Ka Tai Loo b, Chun Keung Mok c, Ming Keung Yuen a, Yu Keung Cheung a,* a
Department of Radiology, Tuen Mun Hospital, Tuen Mun, Hong Kong, NT, PR China Department of Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong, NT, PR China c Department of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong, NT, PR China b
Received 28 December 1999; accepted 8 May 2000
Abstract A 23-year-old female university student was presented with recent onset of non-specific headache and dizziness. She had no neurological deficit on neurological examination and magnetic resonance imaging of the brain revealed diffuse enhancement in the basal cisterns and cerebral sulci. She was treated as tuberculous meningitis but she did not improve and developed respiratory arrest. Autopsy showed primary multifocal leptomeningeal gliomatosis. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Primary multifocal leptomeningeal gliomatosis; Magnetic resonance imaging; Meningitis
1. Introduction Primary diffuse leptomeningeal gliomatosis (PDLG) is an extremely rare condition with dismal prognosis. The presenting symptoms and imaging findings are non-specific which frequently lead to the incorrect diagnosis of chronic meningitis. We present a case of PDLG and review the literature of this condition.
2. Case report A 23-year-old female university student was admitted to our hospital with headache and dizziness for 1 month. She was well all along and had no relevant family, travel or drug history. Systemic examination and neurological examination were normal on admission. Investigations including non-enhanced computed tomography (NECT) scan of the brain were also normal. Her symptoms subsided spontaneously and she was discharged 2 days after admission. However, her * Corresponding author. Tel.: + 85-2-24685163; fax: +85-224632551. E-mail address:
[email protected] (Y. Keung Cheung).
symptoms relapsed after discharge and were associated with nausea and vomiting. She was re-admitted to our hospital 10 days later because of generalized tonic – clonic convulsion. Examination revealed a mildly confused patient with no neck rigidity or any focal neurological deficit. Fundal examination revealed blurred disc margin. Electroencephalogram (EEG) of the patient showed generalized asynchronous slowing of background waves, which was suggestive of encephalopathy or encephalitis. Her blood results showed leucophilia of 15.6× 109/l, elevated erythrocyte sedimentation rate (ESR) of 25 min/h and raised C-Reactive Protein (CRP) level of 69.5 mg/l. Another NECT scan of the brain was performed and the result was again normal. Lumbar puncture was withheld because of the clinical suspicion of raised intracranial pressure. Treatment was started with the provisional diagnoses of encephalitis or sepsis of unknown origin. Rocephin, ampicillin and acyclovir were started empirically. She developed right 6th cranial nerve palsy and later left 6th and 7th cranial nerve palsies in the following few days. Lumbar puncture was then performed and revealed normal cerebrospinal fluid (CSF) pressure but grossly elevated protein level of 5.7 g/l and low glucose level of 0.8 mmol/l (concurrent serum level was 8.3 mmol/l).
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E. Yik Kong Tsui et al. / European Journal of Radiology 37 (2001) 5–7
Fig. 1. (A) Axial contrast-enhanced MR image shows enhancement in the cerebellar vermis, interpeduncular and ambient cisterns. (B) Coronal contrast-enhanced MR image illustrates abnormal enhancement in the cerebral sulci bilaterally.
CSF red cells were B1/min3 and white blood cells were 1/min3. There was no tumor cells detected. Gram stain was inconclusive because of abundant proteinous deposit. Acid Fast Bacilli smear, culture and tuberculous DNA by Polymerase Chain Reaction (PCR) technique were all negative. Non-enhanced cranial magnetic resonance imaging (MRI) was normal. Post gadolinium images revealed diffuse enhancement in cerebral sulci, cerebellar vermis, basal, prepontine and ambient cisterns with no evidence of intraparenchymal involvement (Fig. 1). Tuberculous meningitis was diagnosed and treatment with isonizaide, rifampicin, pyrazinamide and amikacin were started. A second CSF examination on day 11 following admission yielded similar result, but with an even higher protein level of 8 g/l. Serial EEG showed gradual normalization but her clinical condition did not improve. She had another generalized tonic –clonic convulsion on day 16 requiring sedation and anti-epileptic treatment. On day 17, she developed respiratory failure after recurrent convulsion and was put on artificial ventilation. She finally succumbed after the development of ventricular fibrillation despite vigorous resuscitation. At autopsy, there was diffuse thickening of the basal leptomeninges, especially prominent at the pontine region. No lesion was noted in the brain parenchyma. Microscopic examination showed complete replacement of the leptomeninges by tumor composed of nests of polygonal tumor cells with markedly pleomorphic hyperchromatic nuclei and variable and variable amounts of eosinophilic cytoplasm. Immunoreactivity for glial fibrillary acidic protein and vimentin was demonstrated in the tumor cells. The tumor also involved the subarachnoid space in the Virchow – Robin spaces (Fig. 2).
Fig. 2. (A) Basal surface of temporal lobe showing leptomeningeal infiltration by tumor cells (arrow) which also invade the gray matter (Haematoxylin and eosin ×120). (B) High magnification showing glioblastoma cells (arrowheads) with pleomorphic hyperchromatic nuclei (Haematoxylin and eosin × 600).
E. Yik Kong Tsui et al. / European Journal of Radiology 37 (2001) 5–7
3. Discussion Leptomeningeal tumors are most commonly caused by meningioma, metastatic meningeal carcinomatosis and spread of tumors arising from the central nervous system. Primary leptomeningeal gliomatosisis is a rare disease entity. Primary diffuse leptomeningeal gliomatosis (PDLG) is even rarer and only ten cases have been reported in the literature [1]. PDLG was first described by Korein et al. and it was believed to be originated from neoplastic transformation of heterotopic neuroglial tissue [2]. The diagnosis of PDLG is established by fulfilling the following three diagnostic criteria set by Cooper and Kemohan, (i) no attachment of the tumor to the brain parenchyma, (ii) no evidence of intraaxial lesions, (iii) the presence of leptomeningeal encapsulation of the tumor [3]. PDLG is more commonly seen in young adult male although it has been reported in children. The clinical features of PDLG include vomiting, headache, papilloedema, diplopia and cranial nerve palsies, altered level of consciousness and spinal cord symptoms. CSF may show a marked increase in protein level, a normal or low glucose level, lymphocytosis and elevated CSF pressure. CT scan of brain may disclose progressive ventricular dilatation and evidence of obstructive hydrocephalus. Leptomeningeal enhancement may be seen following intravenous contrast administration. With the advent of MRI, it appears to be the imaging modality of choice for early detection of the lesions. Typical MRI findings are abnormal leptomeningeal thickening and enhancement at multiple sites including the spinal cord following intravenous gadolinium [4,5]. The clinical features, laboratory and imaging findings are non-specific and frequently lead to the incorrect diagnosis of aseptic or sub-acute meningitis. The diagnosis is usually established by meningeal biopsy or at autopsy. A high index of suspicion is necessary in making the diagnosis early in the course of the disease. A non-specific prodromal period of 1 – 2 months’ duration followed by progressive neurological deterioration has been proposed as suggestive of PDLG [6]. In addition, the sensitivity of CSF cytology can be improved by the use of glial fibrillary acidic protein (GFAP) immunoperoxidase labeled antibody. In our case, the
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presence of leptomeningeal enhancement in the basal cisterns and cerebral sulci on MR images raised the diagnosis of tuberculous meningitis. The differential diagnoses of these findings included leptomeningeal carcinomatosis, fungal infection, leukemia, lymphoma and leptomeningeal seeding from primary tumor of the central nervous system. The prognosis of PDLG is poor and probably attributed by the widespread dissemination of the tumor at presentation [7]. There was only one case report of complete remission after aggressive radiotherapy and chemotherapy [8]. Our case serves as a reminder to clinicians that PDLG has to be considered in cases of aseptic meningitis, in the absence of primary malignancy and clinical evidence of infection and early meningeal biopsy is necessary for definitive diagnosis.
Acknowledgements We would like to thank Y.C. Chan (Department of Radiology, Tuen Mun Hospital) for his invaluable assistance with the manuscript.
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