73
Letters to the Editor sensory disturbances closely resembling an ischaemic process. Intra-arterial embolism of an aneurysmal sac thrombosis is considered a possible cause of transient ischaemic deficit or completed stroke in patients with unruptured, intracranial aneurysms.45 In our case the demonstration by MRI of intraluminal thrombotic material inside the aneurysm gives support to the view that thrombi may have dislodged from the clot and embolised into the distal vessels.5 Alternatively the thrombosis process may extend from the aneurysm and involve the lumen of an artery arising from the basilar artery and so cause ischaemia. On the other hand, it seems unlikely that platelet embolisation from an extracranial source was the cause because the patient had no stenosis or ulceration in these vessels; neither a cardiac source, systemic hypotension, nor underlying conditions predisposing to hypercoagulability were identified. Regardless of the physiopathological mechanisms, the case reported shows that the PSS syndrome can occur secondarily to a basilar aneurysm and provides another example of the many potential aetiologies of lacunar syndromes. A NICOLAI LG LAZZARINO Department of Neurology, Ospedale Civile di Gorizia
Correspondence to: Dr Nicolai, Via Eleonora Duse 22, 34170 Gorizia Italy. 1 Fisher CM. Pure sensory stroke involving face, arm and leg. Neurology 1965;15:76-80. 2 Decroix JP, Graveleau Ph, Masson M, Cambier
Figure Top-contrast-enhanced CT scan showing round area of increased density in upper interpeduncularfossa. Middle-MRI (Sagittal, T2 weighted) showing aneurysm extendingfrom upper pons to inferior aspect of third ventricle compressing left cerebral peduncle. Bottom-MRI (Axial, T2 weighted) shows hyperintense images within aneurysm suggesting clot inside its lumen.
have been found at necropsy or during neurological evaluation for other reasons. In our case the association of ischaemic attacks with an aneurysm in the appropriate vascular distribution without any evidence of other abnormalities of the CNS strongly suggests a causal relation rather than an incidental finding. Transient neurological disorders resembling TIAs or reversible ischaemic neurological deficits have been described in patients with intracranial unruptured aneurysms, but although an ischaemic process was suspected in all cases, the exact pathophysiological mechanisms of these disturbances remain obscure.4 Focal neurological events have been attributed to the compressive effects of large intracranial aneurysms. The abrupt onset of symptoms may occur because enlarging aneurysms acutely obstruct a penetrating branch of the basilar artery within the confines of the aneurysm. A mechanism of direct compression on the adjacent cerebral structures seems unlikely in our patient as he showed transient
J. Infarctus cerebraux et deficit sensitif pur. Rev Neurol 1989;145:111-6. 3 Azouvi Ph, Tougeron A, Hussonois C, Schouman-Claeys E, Bussel B, Held JP. Pure sensory stroke due to midbrain haemorrhage limited to the spino-thalamic pathway. J Neurol Neurosurg Psychiatry 1989;52: 1427-8. 4 Fisher M, Davidson RI, Marcus EM, Transient focal cerebral ischemia as a presenting manifestation of unruptured cerebral aneurysm. Ann Neurol 1980;8:367-72. 5 Fisher M, Smith TW, Jakobs R. Pure motor hemiplegia secondary to a saccular basilar artery aneurysm. Stroke 1988;91:229-33.
Ectopic parasellar pituitary adenoma with subarachnoid seeding There are very few descriptions of an ectopic supra- or parasellar pituitary adenoma in a patient with a normal intrasellar pituitary gland. In one case the tumour originated in the pars tuberalis,' in another in the parasellar region, and in a third case the tumour arose either in the sphenoid or in the pars tuberalis.3 We report a further case of ectopic parasellar pituitary adenoma which was complicated by subarachnoid seeding 13 years after initial treatment by craniotomy, radiotherapy and
systemic chemotherapy. In 1975 a 45 year old man who had been impotent for one and a half years was found to have a left sided oculomotor paresis. Radiographs showed a normal pituitary fossa and paranasal sinuses. Orbital venography, carotid angiography and basal cisternography suggested a left parasellar lesion. The patient's hormonal iodine concentration was low (0-23 m mol/L; normal range 0-24-048), his serum prolactin concentration was not determined. Craniotomy disclosed two mucoid tumours. One was pea-sized, seemed to infiltrate into the left oculomotor nerve near its entrance into the cavernous sinus, and was
removed incompletely. The other tumour was bean-sized and located under the left optic nerve; this tumour was removed completely. The pathologists who were consulted had difficulty in making a definite diagnosis: reticulosarcoma and malignant epithelial tumour were suggested. An extensive search did not detect tumours in other sites. The patient was treated with radiotherapy followed by systemic chemotherapy (12 courses of cyclophosphamide and vincristin). After whole brain irradiation up to 23-50 Gy treatment coned down to (para)sellar areas was given up to 60 Gy. Special attention was paid to include the suprasellar area for up to 3 cm, and the whole of the sphenoid; the clivus was only partly irradiated. In 1979 a CT of the brain revealed nothing abnormal. In 1988, the patient was found in an unkempt condition and was admitted in a delirious state and with neck rigidity. Body temperature was 34 7°C. T4, FTA index and T3 uptake were 65 nmol/l (N = 80-150), 55 nmol/l (N = 70-170) and 0-66 nmol/i (N = 0-95-1-20) respectively. Serum TSH was normal. CSF protein was 20 gram/l, cell count was normal and cytological examination of the fluid did not identify tumour cells. The patient's condition improved with general supportive treatment and levothyroxin and dexaomethasone. CT and MRI of the brain and spinal cord identified a mass located anterolateral to the pons and medulla oblongata, mainly on the right side and extending down to the sixth cervical vertebra. Intraspinal lesions were also present in the high and mid thoracic regions. To obtain a tissue diagnosis, stereotactic biopsies were taken under local anaesthesia. Smears made during this procedure suggested a pituitary adenoma. The patient died suddenly on the third postoperative day. At necropsy the immediate cause of death appeared to be aspiration of food. No other abnormalities were found outside the central nervous system. Grossly as well as microscopically no abnormalities were found in the para- and suprasellar region, pituitary fossa or sphenoid sinuses. Mucoid tumour tissue was found in the lesions shown by CT and MRI. Histopathologically, the tumour consisted of sheets of medium-sized epithelial cells with round or ovoid nuclei surrounded by faintly stained agranular cytoplasm. Mitotic figures were rare and nuclear polymorphism was inconspicuous. Immunoreactions for keratin and NSE were positive, and for S-100 weakly positive. Very few cells reacted positively for chromogranin A. Between 10-25% of the cells reacted strongly for prolactin, less than 10% for growth hormone. Ultrastructural examination of stereotactic biopsy showed a few 100-200 nm dense granules, often surrounded by a membrane (figure). The histological appearance of the specimens obtained from 1975 and 1988 were identical; the paraffin blocks from 1975 were not available for further study. The diagnosis therefore was of an ectopic parasellar pituitary adenoma, with a normal intrasellar pituitary producing leptomeningeal seeding. The coexistence of an ectopic supra- or parasellar pituitary adenoma with a normal intrasellar pituitary gland is not surprising in view of the recognition by Hori4 of "aberrant" adenohypophyseal cells in the leptomeninges surrounding the pituitary stalk and infundibulum. These cells were found in all foetuses examined and in 75% of adult necropsies. In the present case, between
74
Letters to the Editor of cancer of the bronchus (526 ng/l). IFNy was also present in the serum of the patient
.......
W. tt
with non-Hodgkin lymphoma (48 ng/l) who had IFNy in the CSF. TNFa was detected in three of four CSF samples but not in the serum of patients with ,meningeal infiltration from malignant melanoma (61, 78, and 166 ng/l) or in CSF in other neoplastic diseases. TNFa was, however, detected in sera from three patients with meningeal carcinomatosis (breast, 534 ng/l; bronchus, 46 ng/l; unknown origin, 118 ng/l) and one patient with non-Hodgkin lymphoma * §. 4t(48t ng/l). None of the CSF or serum samples contained both IFNy and TNFa. TNFa may mediate inflammation and tissue destruction in bacterial meningitis, par-
ticularly
sk
Figure Photomicrographs showing immunostainings for chromogranin A (left upper, 1320 x), prolactin (right upper, 1320 x ),growth hormone (left lower, 1320 x ) tand ultrastructural detail of secretory granules (right lower, 36-600 x ).
10-25% of the tumour cells contained prolactin and it is possible that the patient's impotence was due to hyperprolactinaemia. The combination of apparently benign histological features followed by seeding through the CSF after 13 years has been described before.5 The tumour tissue deposits occurred in sites at which the radiotherapy dose was low or to which radiotherapy was not given. This suggests that a pituitary adenoma with potential to metastasise may respond to radiotherapy. Dissemination of tumour during surgery cannot be excluded as a cause of arachnoid seeding but such seeding has been observed in patients who have not previously had operation. We conclude that the surgeon as well as the pathologist should be aware that "ectopic" suprasellar adenohypophyseal cells and adenomas occur in the supra- and parasellar region. The diagnosis can be made by the application of immunohistochemistry and electronmicroscopy to biopsy material. This tumour may be hormonally active so that
endocrinological studies should be performed before operation.
Tumour necrosis factor-a in malignant melanomatous meningitis
munotherapy in disseminated malignancies. Our study included CSF and serum samples, stored at - 70°C after lumbar puncture and centrifugation without further processing, from patients with diffuse leptomeningeal metastasis from cancer of the breast (14), bronchus (7), ovary, cervix, prostate, kidney, stomach (1 each), and unknown origin (4), malignant melanoma (4), nonHodgkin lymphoma (9), multiple myeloma (1), and Hodgkin's disease (1). Commercial ELISA kits were purchased from British Biotechnology, Oxford, UK, (TNFa), and Endogen, Boston, USA (IFNy). Sensitivity was 50 ng/l for IFNy and 40 ng/l for TNFa. IFNy was found in the CSF in carci-
Meningeal infiltration by neoplastic cells is an ominous prognostic sign in patients suffering from systemic cancer. After carcinoma of the breast and bronchus, malignant melanoma is the third most common primary tumour in patients with diffuse leptomeningeal metastasis.'
Intrathecal synthesis of IgG and detection of oligoclonal immunoglobulin bands on isoelectric focussing gels of CSF in meningeal carcinomatosis, suggest immune recognition of tumour cells within the CNS.' We determined the levels of two cytokines, tumour necrosis factor-a (TNFa) and interferon
(IFNy), in paired serum and CSF samples obtained from 45 patients with meningeal malignancies. Cytokines, for example, interleukins, interferons, and TNFa, are
gamma
multifunctional messenger molecules
rently evaluated for
new
cur-
approaches of im-
W KAMPHORST
Department of Neuropathology
JG WOLBERS H PONSSEN Department of Neurosurgery ABMF KARIM Department of Radiotherapy, Free University Hospital, PO Box 7057, 1007 MB Amsterdam, The Netherlands
severe
meningococcal disease,'
inflammatorydemyelination,4andtumourcell cytotoxicity in vitro. To our knowledge, this is the first report on TNFa in meningeal malignancies. New approaches to an immunotherapy of malignant melanoma are evolving rapidly, and are based on specific immunogenic features ofthis malignancy, for example, inhibition of tumour cell proliferation in vitro by IFNy and TNFa.6 Although elevated levels of TNFa in the CSF of patients with malignant melanomatous meningitis are still a preliminary finding, the lack of similar results in a large control group ofother meningeal malignancies confirms the existence of special interactions between melanoma cells and the host's immune system. This warrants further investigation. MICHAEL WELLER ANDREAS STEVENS NORBERT SOMMER HORST WIETHOLTER Department ofNeurology, University of Tabingen, Germany
Correspondence to: Dr Michael Weller. 1
2
3 4 5
Rothman LM, Sher J, Quencer RM, Tenner MS. Intracranial ectopic pituitary adenoma. J Neurosurg 1976;44:96-9. Bonner RA, Mukai K, Oppenheimer JH. Two unusual variants of Nelson's syndrome. J Clin Endocrinol Metab 1979;43:23-9. Kepes JJ, Fritzlen TJ. Large invasive chromophobe adenoma with well-preserved pituitary gland. Neurology 1964;14:537-41. Hori A. Suprasellar peri-infundibular ectopic adenohypophysis in fetal and adult brains. J Neurosurg 1985;63:113-5. Kuroki M, Tanaka R, Yokoyama M, Shimbo Y, Ikuta F. Subarachnoid dissemination of a pituitary adenoma. SurgNeurol 1987;28:71-6.
nomatosis from two cases of breast cancer (322 and 899 ng/l), one case of cancer of unknown origin (639 ng/l), and one case of
non-Hodgkin lymphoma (66 ng/l). IFNy in serum was positive in two cases of cancer of the breast (56 and 901 ng/l); neither of which had detectable IFNy in the CSF, and one case
1 Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1980;49:759-72. 2 Schipper HI, Bardosi A, Jacobi C, Felgenhauer K. Meningeal carcinomatosis: Origin of local IgG production in the CSF. Neurology 1988; 38:413-6. 3 Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med 1989;170:1859-67. 4 Brosnan CF, Selmaj K, Raine CS. Hypothesis: a role for tumor necrosis factor in immunemediated demyelination and its relevance to multiple sclerosis. J Neuroimmunol 1988;18: 87-94. 5 Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A. Antigen presentation and tumor cytotoxicity by interferon-ytreated microglial cells. Eur J Immunol 1987; 17:1271-8. 6 Mortarini R, Belli F, Parmiani G, Anichini A. Cytokine-mediated modulation of HLA-class II. ICAM-I, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIl-B, rTNF-a, rIL4 and their combinations. Int J Cancer 1990;45:334-41.
Partial self induced seizures: an uncommon motivation for auto-induction Some epileptic patients may self induce their seizures. In most instances, these are people affected by photosensitive primary generalised epilepsy, in whom self induction is by intermittent photic stimulation (IPS) or, more rarely, pattern stimulation or eye closure. Documented reports have increased recently due to the availability of IPS from
Letters to the Editor sensory disturbances closely resembling an ischaemic process. Intra-arterial embolism of an aneurysmal sac thrombosis is considered a possible cause of transient ischaemic deficit or completed stroke in patients with unruptured, intracranial aneurysms.45 In our case the demonstration by MRI of intraluminal thrombotic material inside the aneurysm gives support to the view that thrombi may have dislodged from the clot and embolised into the distal vessels.5 Alternatively the thrombosis process may extend from the aneurysm and involve the lumen of an artery arising from the basilar artery and so cause ischaemia. On the other hand, it seems unlikely that platelet embolisation from an extracranial source was the cause because the patient had no stenosis or ulceration in these vessels; neither a cardiac source, systemic hypotension, nor underlying conditions predisposing to hypercoagulability were identified. Regardless of the physiopathological mechanisms, the case reported shows that the PSS syndrome can occur secondarily to a basilar aneurysm and provides another example of the many potential aetiologies of lacunar syndromes. A NICOLAI LG LAZZARINO Department of Neurology, Ospedale Civile di Gorizia
Correspondence to: Dr Nicolai, Via Eleonora Duse 22, 34170 Gorizia Italy. 1 Fisher CM. Pure sensory stroke involving face, arm and leg. Neurology 1965;15:76-80. 2 Decroix JP, Graveleau Ph, Masson M, Cambier
Figure Top-contrast-enhanced CT scan showing round area of increased density in upper interpeduncularfossa. Middle-MRI (Sagittal, T2 weighted) showing aneurysm extendingfrom upper pons to inferior aspect of third ventricle compressing left cerebral peduncle. Bottom-MRI (Axial, T2 weighted) shows hyperintense images within aneurysm suggesting clot inside its lumen.
have been found at necropsy or during neurological evaluation for other reasons. In our case the association of ischaemic attacks with an aneurysm in the appropriate vascular distribution without any evidence of other abnormalities of the CNS strongly suggests a causal relation rather than an incidental finding. Transient neurological disorders resembling TIAs or reversible ischaemic neurological deficits have been described in patients with intracranial unruptured aneurysms, but although an ischaemic process was suspected in all cases, the exact pathophysiological mechanisms of these disturbances remain obscure.4 Focal neurological events have been attributed to the compressive effects of large intracranial aneurysms. The abrupt onset of symptoms may occur because enlarging aneurysms acutely obstruct a penetrating branch of the basilar artery within the confines of the aneurysm. A mechanism of direct compression on the adjacent cerebral structures seems unlikely in our patient as he showed transient
J. Infarctus cerebraux et deficit sensitif pur. Rev Neurol 1989;145:111-6. 3 Azouvi Ph, Tougeron A, Hussonois C, Schouman-Claeys E, Bussel B, Held JP. Pure sensory stroke due to midbrain haemorrhage limited to the spino-thalamic pathway. J Neurol Neurosurg Psychiatry 1989;52: 1427-8. 4 Fisher M, Davidson RI, Marcus EM, Transient focal cerebral ischemia as a presenting manifestation of unruptured cerebral aneurysm. Ann Neurol 1980;8:367-72. 5 Fisher M, Smith TW, Jakobs R. Pure motor hemiplegia secondary to a saccular basilar artery aneurysm. Stroke 1988;91:229-33.
Ectopic parasellar pituitary adenoma with subarachnoid seeding There are very few descriptions of an ectopic supra- or parasellar pituitary adenoma in a patient with a normal intrasellar pituitary gland. In one case the tumour originated in the pars tuberalis,' in another in the parasellar region, and in a third case the tumour arose either in the sphenoid or in the pars tuberalis.3 We report a further case of ectopic parasellar pituitary adenoma which was complicated by subarachnoid seeding 13 years after initial treatment by craniotomy, radiotherapy and
systemic chemotherapy. In 1975 a 45 year old man who had been impotent for one and a half years was found to have a left sided oculomotor paresis. Radiographs showed a normal pituitary fossa and paranasal sinuses. Orbital venography, carotid angiography and basal cisternography suggested a left parasellar lesion. The patient's hormonal iodine concentration was low (0-23 m mol/L; normal range 0-24-048), his serum prolactin concentration was not determined. Craniotomy disclosed two mucoid tumours. One was pea-sized, seemed to infiltrate into the left oculomotor nerve near its entrance into the cavernous sinus, and was
removed incompletely. The other tumour was bean-sized and located under the left optic nerve; this tumour was removed completely. The pathologists who were consulted had difficulty in making a definite diagnosis: reticulosarcoma and malignant epithelial tumour were suggested. An extensive search did not detect tumours in other sites. The patient was treated with radiotherapy followed by systemic chemotherapy (12 courses of cyclophosphamide and vincristin). After whole brain irradiation up to 23-50 Gy treatment coned down to (para)sellar areas was given up to 60 Gy. Special attention was paid to include the suprasellar area for up to 3 cm, and the whole of the sphenoid; the clivus was only partly irradiated. In 1979 a CT of the brain revealed nothing abnormal. In 1988, the patient was found in an unkempt condition and was admitted in a delirious state and with neck rigidity. Body temperature was 34 7°C. T4, FTA index and T3 uptake were 65 nmol/l (N = 80-150), 55 nmol/l (N = 70-170) and 0-66 nmol/i (N = 0-95-1-20) respectively. Serum TSH was normal. CSF protein was 20 gram/l, cell count was normal and cytological examination of the fluid did not identify tumour cells. The patient's condition improved with general supportive treatment and levothyroxin and dexaomethasone. CT and MRI of the brain and spinal cord identified a mass located anterolateral to the pons and medulla oblongata, mainly on the right side and extending down to the sixth cervical vertebra. Intraspinal lesions were also present in the high and mid thoracic regions. To obtain a tissue diagnosis, stereotactic biopsies were taken under local anaesthesia. Smears made during this procedure suggested a pituitary adenoma. The patient died suddenly on the third postoperative day. At necropsy the immediate cause of death appeared to be aspiration of food. No other abnormalities were found outside the central nervous system. Grossly as well as microscopically no abnormalities were found in the para- and suprasellar region, pituitary fossa or sphenoid sinuses. Mucoid tumour tissue was found in the lesions shown by CT and MRI. Histopathologically, the tumour consisted of sheets of medium-sized epithelial cells with round or ovoid nuclei surrounded by faintly stained agranular cytoplasm. Mitotic figures were rare and nuclear polymorphism was inconspicuous. Immunoreactions for keratin and NSE were positive, and for S-100 weakly positive. Very few cells reacted positively for chromogranin A. Between 10-25% of the cells reacted strongly for prolactin, less than 10% for growth hormone. Ultrastructural examination of stereotactic biopsy showed a few 100-200 nm dense granules, often surrounded by a membrane (figure). The histological appearance of the specimens obtained from 1975 and 1988 were identical; the paraffin blocks from 1975 were not available for further study. The diagnosis therefore was of an ectopic parasellar pituitary adenoma, with a normal intrasellar pituitary producing leptomeningeal seeding. The coexistence of an ectopic supra- or parasellar pituitary adenoma with a normal intrasellar pituitary gland is not surprising in view of the recognition by Hori4 of "aberrant" adenohypophyseal cells in the leptomeninges surrounding the pituitary stalk and infundibulum. These cells were found in all foetuses examined and in 75% of adult necropsies. In the present case, between
74
Letters to the Editor of cancer of the bronchus (526 ng/l). IFNy was also present in the serum of the patient
.......
W. tt
with non-Hodgkin lymphoma (48 ng/l) who had IFNy in the CSF. TNFa was detected in three of four CSF samples but not in the serum of patients with ,meningeal infiltration from malignant melanoma (61, 78, and 166 ng/l) or in CSF in other neoplastic diseases. TNFa was, however, detected in sera from three patients with meningeal carcinomatosis (breast, 534 ng/l; bronchus, 46 ng/l; unknown origin, 118 ng/l) and one patient with non-Hodgkin lymphoma * §. 4t(48t ng/l). None of the CSF or serum samples contained both IFNy and TNFa. TNFa may mediate inflammation and tissue destruction in bacterial meningitis, par-
ticularly
sk
Figure Photomicrographs showing immunostainings for chromogranin A (left upper, 1320 x), prolactin (right upper, 1320 x ),growth hormone (left lower, 1320 x ) tand ultrastructural detail of secretory granules (right lower, 36-600 x ).
10-25% of the tumour cells contained prolactin and it is possible that the patient's impotence was due to hyperprolactinaemia. The combination of apparently benign histological features followed by seeding through the CSF after 13 years has been described before.5 The tumour tissue deposits occurred in sites at which the radiotherapy dose was low or to which radiotherapy was not given. This suggests that a pituitary adenoma with potential to metastasise may respond to radiotherapy. Dissemination of tumour during surgery cannot be excluded as a cause of arachnoid seeding but such seeding has been observed in patients who have not previously had operation. We conclude that the surgeon as well as the pathologist should be aware that "ectopic" suprasellar adenohypophyseal cells and adenomas occur in the supra- and parasellar region. The diagnosis can be made by the application of immunohistochemistry and electronmicroscopy to biopsy material. This tumour may be hormonally active so that
endocrinological studies should be performed before operation.
Tumour necrosis factor-a in malignant melanomatous meningitis
munotherapy in disseminated malignancies. Our study included CSF and serum samples, stored at - 70°C after lumbar puncture and centrifugation without further processing, from patients with diffuse leptomeningeal metastasis from cancer of the breast (14), bronchus (7), ovary, cervix, prostate, kidney, stomach (1 each), and unknown origin (4), malignant melanoma (4), nonHodgkin lymphoma (9), multiple myeloma (1), and Hodgkin's disease (1). Commercial ELISA kits were purchased from British Biotechnology, Oxford, UK, (TNFa), and Endogen, Boston, USA (IFNy). Sensitivity was 50 ng/l for IFNy and 40 ng/l for TNFa. IFNy was found in the CSF in carci-
Meningeal infiltration by neoplastic cells is an ominous prognostic sign in patients suffering from systemic cancer. After carcinoma of the breast and bronchus, malignant melanoma is the third most common primary tumour in patients with diffuse leptomeningeal metastasis.'
Intrathecal synthesis of IgG and detection of oligoclonal immunoglobulin bands on isoelectric focussing gels of CSF in meningeal carcinomatosis, suggest immune recognition of tumour cells within the CNS.' We determined the levels of two cytokines, tumour necrosis factor-a (TNFa) and interferon
(IFNy), in paired serum and CSF samples obtained from 45 patients with meningeal malignancies. Cytokines, for example, interleukins, interferons, and TNFa, are
gamma
multifunctional messenger molecules
rently evaluated for
new
cur-
approaches of im-
W KAMPHORST
Department of Neuropathology
JG WOLBERS H PONSSEN Department of Neurosurgery ABMF KARIM Department of Radiotherapy, Free University Hospital, PO Box 7057, 1007 MB Amsterdam, The Netherlands
severe
meningococcal disease,'
inflammatorydemyelination,4andtumourcell cytotoxicity in vitro. To our knowledge, this is the first report on TNFa in meningeal malignancies. New approaches to an immunotherapy of malignant melanoma are evolving rapidly, and are based on specific immunogenic features ofthis malignancy, for example, inhibition of tumour cell proliferation in vitro by IFNy and TNFa.6 Although elevated levels of TNFa in the CSF of patients with malignant melanomatous meningitis are still a preliminary finding, the lack of similar results in a large control group ofother meningeal malignancies confirms the existence of special interactions between melanoma cells and the host's immune system. This warrants further investigation. MICHAEL WELLER ANDREAS STEVENS NORBERT SOMMER HORST WIETHOLTER Department ofNeurology, University of Tabingen, Germany
Correspondence to: Dr Michael Weller. 1
2
3 4 5
Rothman LM, Sher J, Quencer RM, Tenner MS. Intracranial ectopic pituitary adenoma. J Neurosurg 1976;44:96-9. Bonner RA, Mukai K, Oppenheimer JH. Two unusual variants of Nelson's syndrome. J Clin Endocrinol Metab 1979;43:23-9. Kepes JJ, Fritzlen TJ. Large invasive chromophobe adenoma with well-preserved pituitary gland. Neurology 1964;14:537-41. Hori A. Suprasellar peri-infundibular ectopic adenohypophysis in fetal and adult brains. J Neurosurg 1985;63:113-5. Kuroki M, Tanaka R, Yokoyama M, Shimbo Y, Ikuta F. Subarachnoid dissemination of a pituitary adenoma. SurgNeurol 1987;28:71-6.
nomatosis from two cases of breast cancer (322 and 899 ng/l), one case of cancer of unknown origin (639 ng/l), and one case of
non-Hodgkin lymphoma (66 ng/l). IFNy in serum was positive in two cases of cancer of the breast (56 and 901 ng/l); neither of which had detectable IFNy in the CSF, and one case
1 Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1980;49:759-72. 2 Schipper HI, Bardosi A, Jacobi C, Felgenhauer K. Meningeal carcinomatosis: Origin of local IgG production in the CSF. Neurology 1988; 38:413-6. 3 Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med 1989;170:1859-67. 4 Brosnan CF, Selmaj K, Raine CS. Hypothesis: a role for tumor necrosis factor in immunemediated demyelination and its relevance to multiple sclerosis. J Neuroimmunol 1988;18: 87-94. 5 Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A. Antigen presentation and tumor cytotoxicity by interferon-ytreated microglial cells. Eur J Immunol 1987; 17:1271-8. 6 Mortarini R, Belli F, Parmiani G, Anichini A. Cytokine-mediated modulation of HLA-class II. ICAM-I, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIl-B, rTNF-a, rIL4 and their combinations. Int J Cancer 1990;45:334-41.
Partial self induced seizures: an uncommon motivation for auto-induction Some epileptic patients may self induce their seizures. In most instances, these are people affected by photosensitive primary generalised epilepsy, in whom self induction is by intermittent photic stimulation (IPS) or, more rarely, pattern stimulation or eye closure. Documented reports have increased recently due to the availability of IPS from
