A 30-year-old, previously healthy female, was first admitted to a local hospital on June 24, 2013 with main complaints of progressive headache, nausea, vomiting, and blurred vision which had persisted for 2 months. On admission, she was afebrile and general physical examination revealed no abnormalities. Her neurological abnormalities included bilateral papilledema, vision impairment, and signs of meningeal irritation. No motor or sensory deficits were seen. Blood tests of routine, biochemistry, coagulation, thyroid function, and various immunological parameters were all in the normal range. Blood antibodies for HIV, syphilis, and tuberculosis were negative. Initial brain MRI revealed a dilated left Sylvian fissure and an abnormal signal on the medial-dorsal side of the left thalamus (Figure 1A). Diffuse enhancement was noticed in the meninges, the left thalamus adjacent ventricular ependyma, the cerebellar tentorium, and the quadrigeminal cistern, whereas no enhancement was identified in the parenchyma (Figures 1B,C). Cerebrospinal fluid (CSF) analysis in the 3-series lumbar punctures revealed opening pressures higher than 400 mmH2O (reference range 80-180 mmH2O), with protein 2.59-5.01 g/L (reference range 0.15-0.45 g/L), glucose 2.20-2.79 mmol/L (reference range 2.5-4.5 mmol/L), chloride 121.1-126.3 mmol/L (reference range 120-130 mmol/L), and WBC 3-6/mL (reference range 0-5/mL) with 80-85% of lymphocytes. Negative results were reported in the following CSF etiological investigations: polymerase chain reaction for tuberculosis, bacteria and fungi cultures, India Ink stain for Cryptococcus, and IgG and IgM antibodies targeting various viruses and parasites. CSF cytology studies did not reveal neoplasm and chest CT and abdomen CT scans did not indicate any abnormality. Tuberculous meningitis was suspected and treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Meanwhile, brain ventricular puncture and drainage were performed and this dramatically attenuated the headache symptoms. The extraventricular drainage device was removed after 2 weeks and shortly thereafter the patient suffered from generalized tonic-clonic seizures. Once the seizures were controlled, a ventricular-peritoneal shunt was placed, resulting in an improvement of the patient's symptoms. Anti-tubercular therapy was given for 2 months, and then it was discontinued once it proved to be ineffective.
In January 2014, the patient's severe headaches returned and her CSF pressure reached 500 mmH2O. Apart from a further decrease of glucose (1.88 mmol/L), her CSF analysis remained essentially unchanged. The brain MRI at this time revealed a round mass in the quadrigeminal cistern, multiple cyst signals in the Sylvian fissures, and the dilated cortical sulci in addition to the lesion in left thalamus. Overall contrast enhancement was present in the cerebral meninges, the cerebellar tentorium, the cyst walls, and the quadrigeminal cistern (Figures 2A,B). The ventricular-peritoneal shunt pressure was adjusted to 200 mmH2O and stereotactic biopsy of the left thalamus was performed. However, the infiltration by a few lymphocytes was the only observation. The patient's condition deteriorated as generalized seizures became more frequent. In April 2014, she was transferred to our hospital. Upon admission, abnormal neurological findings included confusion, slow light perception, limited abduction of both eyes, grade IV of muscle strength of the right arm, general hyperactive tendon reflexes in both legs, positive Babinski's sign on the right side, and positive meningeal signs. The third brain MRI, performed at this time, showed a non-contrasted, non-cystic lesion in the left paraventricular white matter and a contrasted cystic lesion in the left basal ganglia. All the previous changes were found to be more pronounced, including the cyst-like signals in the dilated cortical sulci, the mass in the quadrigeminal cistern, and the enlarged subarachnoid space, and general meningeal enhancement in the brain and upper segment of the cervical spinal cord (Figures 3A-C). Magnetic resonance spectroscopy (MRS) indicated a Cho/Cr wave ratio higher than 2.5 in the left thalamus and basal ganglia area (Figure 3D), and 1.0 in the right symmetric area that appeared normal on MRI (Figure 3E). Brain biopsy of the left temporal lobe was performed and spindle-shaped tumor cells were found to be spreading into the leptomeninges and subarachnoid space, which were strongly positive for glial fibrillary acidic protein (GFAP) and S100, partly positive for OLIG2 and P53, and negative for IDH1(R132H), ARTX, and NeuN (Figure 4). Ki-67 reactivity in tumor tissue was about 5%. According to 2016 World Health Organization (WHO), classification of tumors of the central nervous system, anaplastic astrocytoma, IDH-wildtype (WHO grade III) was confirmed. Combined with the extensive changes in brain MRI, PDLG was diagnosed. The patient refused treatment and was discharged from the hospital. She died 2 months later.