In 1999 at age 32 years, this man had progressive headache and diplopia due to an obstructive hydrocephalus caused by a pineal tumour. Following resection a pineoloma with malignant histological features was diagnosed. MRI of the craniospinal axis and CSF examination demonstrated no other tumour localizations. He was subsequently treated with craniospinal irradiation (36 Gy in 20 fractions with a boost of 18 Gy to the original tumour site). Following a minor head trauma 4 years after RT he developed increasing headache over the following days and a left hemianopia. No tumour recurrence was observed on MRI, nor in the cerebrospinal fluid (CSF) (Table 1). Additional imaging ruled out ischemic stroke, vertebral artery dissection and venous sinus thrombosis. However, on MRI, gyral thickening of the right parieto-occipital cortex with contrast enhancement was seen (Fig. 1a, b). During hospitalisation he developed several generalized seizures with persistent post-ictal weakness of the left arm and confusion, lasting for several weeks. He was treated with valproate and levetiracetam. EEG showed slowing over the right hemisphere but no epileptic activity. The observed MRI abnormalities recovered over the weeks thereafter, with concomitant clinical improvement (Fig. 1c, d).

Two years later he developed a similar clinical episode for which he was admitted once more, this time without seizures. The same imaging abnormalities were observed which resolved once again over the following months without any treatment. Again, no tumour recurrence could be demonstrated.

However, in 2008, 8 years after the initial presentation he did develop spinal leptomeningeal metastases, for which he was treated with focal RT and systemic chemotherapy.

In 1997 at age 50 years, this man was treated for small cell lung cancer and two brain metastases with systemic chemotherapy and whole-brain radiation (30 Gy in 10 fractions). Ten years later he developed slowly progressive headache, and a few weeks later he woke up with an expressive dysphasia. During hospitalization he developed a right sided hemiparesis with right hemianopia and he suffered from frequent focal epileptic seizures of the right arm and leg, for which he received valproate and levetiracetam. MRI showed focal gyral thickening and enhancement of the left parieto-occipital lobe where metastases had not been observed previously (Fig. 2a–d). Apart from diffuse leukoencephalopathy, presumably due to the earlier brain radiotherapy, there were no signs of recurrent brain metastases. Repeated CSF analysis showed a slightly elevated protein level, but no leptomeningeal metastases (Table 1). There were no clues for extracranial tumour recurrence. During the hospital stay he had a gradual clinical improvement and was discharged fully recovered. A follow-up MRI 3 months after discharge also showed complete resolution of the abnormalities in the left parieto-occipital cortex (Fig. 2e, f).

In 1997 at the age of 42 years, this man suffered from an epileptic seizure caused by an anaplastic oligodendroglioma in the left hemisphere. The tumour was resected and he subsequently received focal brain radiation (60 Gy in 30 fractions). He was discharged from hospital on valproate. Two years later he was admitted to the hospital twice within a short time period with reversible neurological deficits: dysphasia, right hemianopia, headache and neglect of his right arm. Imaging showed no signs of recurrent tumour, but possibly a small infarction in the left occipital region and some diffuse white matter disease, possibly due to radiation. An EEG showed no epileptic activity. Diagnosis of reversible ischemic neurological deficit was hypothesized, possibly due to former radiotherapy.

Three years thereafter he was again taken into hospital with focal epileptic seizures of the right side of his face. He suffered from headache, progressive aphasia, right hemianopia and mild paresis of his right arm and leg. An MRI scan now showed diffuse cortical enhancement of the left occipital and temporal cortex (Fig. 3a, b). This enhancement disappeared on a subsequent MRI performed 8 days later (Fig. 3c, d). An EEG showed no epileptic activity. Clinically, he recovered substantially.

Three years later he was again admitted to hospital because of a new episode of worsening aphasia and paresis of his right arm and leg.

MR imaging, similar to 3 years earlier, demonstrated diffuse cortical enhancement of the left occipital and temporal cortex (Fig. 3e, f). Although CSF examination showed some atypical cells, he again partially recovered spontaneously and almost completely, making leptomeningeal seeding unlikely (Table 1). A follow-up MRI scan performed 1 month later again showed complete disappearance of the contrast enhancement (Fig. 3g, h), and he recovered afterwards in a rehabilitation centre. On longer follow-up, he was treated successfully with temozolomide chemotherapy for local tumour recurrence.

In 1999 at the age of 34 years, this man suffered from an epileptic seizure caused by a right temporal anaplastic astrocytoma. The tumour was resected and he subsequently had focal brain radiation (50 Gy in 20 fractions). In the following 5 years he had infrequent focal seizures of the left arm but no tumour recurrence was observed on repeated MRI. Five years after initial treatment, however, he developed a progressive clumsy left hand, left-sided facial paresis and dysarthria in combination with an increase of focal seizures. An EEG showed nearly continuous epileptic discharges diffusely over the right hemisphere. He was treated with intravenous clonazepam and valproate. The MRI demonstrated no tumour recurrence but a gyriform enhancement and swelling of the right parieto-temporal cortex (Fig. 4a–f).

CSF examination was, besides a slightly elevated protein level, completely normal (Table 1). Over the following weeks the focal seizures disappeared and the left sided weakness improved. The patient was discharged from hospital on valproate and nearly complete resolution of the clinical picture. The abnormalities on MRI did partially resolve (Fig. 4g, h). Three months later, a new MRI was suggestive for recurrent tumour in the right temporal lobe, showing several nodular enhancements. A biopsy confirmed recurrent high-grade glioma, for which he was treated with temozolomide. Following chemotherapy treatment, the abnormal gyral and leptomeningeal enhancement temporarily disappeared, but recurred for which PCV chemotherapy was started. Again, a complete response ensued. Ten years after the initial diagnosis of anaplastic astrocytoma he developed left hemianopia and a clumsy left hand, but had no seizures. On MRI a right occipital contrast enhancing tumour was found, suggestive for recurrent tumour. Resection was planned, but pre-operative imaging showed the lesion to be smaller and an open biopsy did not confirm active tumour growth. Postoperatively he suffered from very frequent focal seizures of the left side of his face and a clumsy left hand, which did not subside until he was put into a propofol induced coma. He completely recovered within several weeks. Follow-up MRI demonstrated the occipital contrast-enhancing to have disappeared completely (Fig. 4i–l). The patient died a year later from tumour recurrence, 11 years after the initial diagnosis.

Protein level in g/l

Interval, years between irradiation and the first symptoms; Gy, radiation dose in Grays; X, number of radiation fractions; WBRT, whole-brain radiation therapy; Focal, focal radiation on the original tumour site