Michael Mokry

Disturbed cerebrospinal fluid circulation after subarachnoid hemorrhage and acute aneurysm surgery.

In 138 patients with ruptured cerebral aneurysms operated on within 48 to 72 hours after subarachnoid hemorrhage, an external ventricular drainage catheter was inserted before craniotomy and was used intermittently during the first week after surgery. In 51 patients, intracranial pressure (ICP) was

Early aneurysm surgery and preventive therapy with intravenously administered nimodipine: a multicenter, double-blind, dose-comparison study

A European, multicenter, prospective, randomized, double-blind, dose-comparison study on preventive therapy with intravenously administered nimodipine was performed to evaluate the efficacy and tolerability of two different doses: 2 and 3 mg/h. Two hundred four patients fulfilled the criteria for enrollment in the study: surgery within 72 hours after the last subarachnoid hemorrhage, and age between 16 and 72 years. All patients who had Hunt and Hess grades of I to III were operated upon; patients who had poor Hunt and Hess grades (IV-V) were operated on according to the surgeons choice. This treatment regimen was associated with a low incidence of delayed neurological dysfunction with no significant difference between the two dosage groups: three patients (1.5%) remained severely disabled and two (1%) moderately disabled due to vasospasm with or without additional complications. Among the patients with Hunt and Hess grades of IV or V, the long-term outcome was favorable (good-fair) for 40% and unfavorable for 60%. Among the patients with grades of I to III, the long-term outcome was favorable for 89% and unfavorable for 11%.

Long-term follow-up of patients with pituitary macroadenomas after postoperative radiation therapy: analysis of tumor control and functional outcome.

Purpose:Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas.Patients and Methods:In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46–54 Gy).Results:After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39–20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy.Conclusion:Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy.Ziel:Ziel der retrospektiven Analyse war die Evaluation der lokalen Tumorkontrolle sowie der hormonellen Normalisierung nach konventioneller postoperativer Strahlentherapie in der Langzeitbeobachtung. Zusätzlich wurden die Inzidenz und der zeitliche Verlauf von Hypophyseninsuffizienzen untersucht.Patienten und Methodik:Zwischen April 1984 and November 1994 wurden 87 Patienten mit Makroadenomen der Hypophyse (nicht-sezernierende Adenome: n = 61, sezernierende Adenome: n = 26) einer postoperativen Strahlentherapie unterzogen. Die Bestrahlung erfolgte mit einer medianen Dosis von 50,4 Gy (Spannweite 46–54 Gy).Ergebnisse:Nach 15 Jahren betrug die lokale Kontrolle bei nicht-sezernierenden Adenomen 93% und bei sezernierenden Adenomen 100%. Eine Normalisierung der hormonellen Hypersekretion konnte bei 24 von 26 Patienten (92%) erreicht werden. Detaillierte Informationen über die hypophysäre Funktion lagen bei 77 Patienten vor. Nach median 10,54 Jahren wurde bei 75 von 77 Patienten (97%) eine Funktionsstörung des Hypophysenvorderlappens diagnostiziert (partieller Hypopituitarismus: n = 28 [36%], Panhypopituitarismus: n = 47 [61%]). Bei 68 von 77 Patienten (88%) zeigte sich eine radiotherapiebedingte Störung hormoneller Funktionen. Die somatotrope Achse war am häufigsten betroffen, gefolgt von der gonadotropen, der thyreotropen und der adrenokortikotropen Achse. In der Analyse des zeitlichen Verlaufs zeigte die gonadotrope Achse als Erste eine funktionelle Störung. 67 Patienten (87%) entwickelten eine substitutionspflichtige Hypophysenvorderlappeninsuffizienz.Schlussfolgerung:Mit der konventionellen postoperativen Strahlentherapie konnte eine ausgezeichnete lokale Kontrolle in der Langzeitbeobachtung erreicht werden. Die Rate an Hypophyseninsuffizienzen erfordert jedoch in einem hohen Prozentsatz eine Hormonersatztherapie und macht lebenslange endokrinologische Kontrollen notwendig.

Long-Term Follow-up of Patients with Pituitary Macroadenomas after Postoperative Radiation Therapy

Purpose:Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas.Patients and Methods:In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46–54 Gy).Results:After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39–20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy.Conclusion:Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy.Ziel:Ziel der retrospektiven Analyse war die Evaluation der lokalen Tumorkontrolle sowie der hormonellen Normalisierung nach konventioneller postoperativer Strahlentherapie in der Langzeitbeobachtung. Zusätzlich wurden die Inzidenz und der zeitliche Verlauf von Hypophyseninsuffizienzen untersucht.Patienten und Methodik:Zwischen April 1984 and November 1994 wurden 87 Patienten mit Makroadenomen der Hypophyse (nicht-sezernierende Adenome: n = 61, sezernierende Adenome: n = 26) einer postoperativen Strahlentherapie unterzogen. Die Bestrahlung erfolgte mit einer medianen Dosis von 50,4 Gy (Spannweite 46–54 Gy).Ergebnisse:Nach 15 Jahren betrug die lokale Kontrolle bei nicht-sezernierenden Adenomen 93% und bei sezernierenden Adenomen 100%. Eine Normalisierung der hormonellen Hypersekretion konnte bei 24 von 26 Patienten (92%) erreicht werden. Detaillierte Informationen über die hypophysäre Funktion lagen bei 77 Patienten vor. Nach median 10,54 Jahren wurde bei 75 von 77 Patienten (97%) eine Funktionsstörung des Hypophysenvorderlappens diagnostiziert (partieller Hypopituitarismus: n = 28 [36%], Panhypopituitarismus: n = 47 [61%]). Bei 68 von 77 Patienten (88%) zeigte sich eine radiotherapiebedingte Störung hormoneller Funktionen. Die somatotrope Achse war am häufigsten betroffen, gefolgt von der gonadotropen, der thyreotropen und der adrenokortikotropen Achse. In der Analyse des zeitlichen Verlaufs zeigte die gonadotrope Achse als Erste eine funktionelle Störung. 67 Patienten (87%) entwickelten eine substitutionspflichtige Hypophysenvorderlappeninsuffizienz.Schlussfolgerung:Mit der konventionellen postoperativen Strahlentherapie konnte eine ausgezeichnete lokale Kontrolle in der Langzeitbeobachtung erreicht werden. Die Rate an Hypophyseninsuffizienzen erfordert jedoch in einem hohen Prozentsatz eine Hormonersatztherapie und macht lebenslange endokrinologische Kontrollen notwendig.

Lymphocytic hypophysitis in the pediatric population

BackgroundLymphocytic hypophysitis (LYH) is a rare inflammatory disease of the pituitary gland that usually affects women in their ante- or immediate postpartum period; males are affected less frequently than females. An autoimmune pathogenesis is suggested. Symptoms comprise anterior and/or posterior pituitary insufficiency of varying degrees. So far, specific characteristics of this rare disease in childhood are not well described.Case historyWe report the case of a 12-year-and-11-month-old boy with histologically confirmed LYH clinically presenting with diabetes insipidus. A high-dose steroid therapy was administered, in which the therapeutic effect was uncertain. His 6-year follow-up is presented.DiscussionThe literature is reviewed for children presenting with LYH; their characteristics, pituitary involvement, and clinical follow-up are listed and discussed.ConclusionEven though magnetic resonance imaging can be highly suspicious for LYH, only surgical exploration can confirm the diagnosis. The efficacy of medical treatment is still controversial; a close follow-up is necessary to control and correct the endocrinological function, if required.

Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle.

Expansive granulomatous lesions in the posterior cranial fossa are rare and have not been reported in conjunction with Lyme disease. We report a patient with verified Borrelia burgdorferi infection who developed a tumor in the cerebellopontine angle. Rapid growth of the tumor led to signs of cerebral compression and to hydrocephalus. Surgical intervention was required despite florid meningitis. The histological examination showed inflammatory, nonspecific granulation tissue. The origin of this tissue is almost certainly causally related to the B. burgdorferi infection. Signs of inflammation resolved rapidly after subtotal resection. The clinical, radiological, and biochemical course is documented. This is the first report of an expansive cerebral lesion in the chronic phase of Lyme disease.

Hyperfractionated radiotherapy and polychemotherapy in brain stem tumors in children

Between October 1989 and Junuary 1991 five children with brain stem tumors were treated with sequential chemo- and radiotherapy. The polychemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. Locally, hyperfractionated radiotherapy was delivered at a total dose of 63.8 Gy (1.1 Gy twice daily, 10 fractions per week). After a median observation time of 11.8 (range 4–23) months from diagnosis three children are alive and without evidence of tumor progression. Two patients died from tumor progression 11 and 16 months respectively after initiation of therapy.

Establishment of clival chordoma cell line MUG-CC1 and lymphoblastoid cells as a model for potential new treatment strategies

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum. Surgery followed by radiotherapy is the standard treatment. As chordomas are resistant to standard chemotherapy, further treatment options are urgently needed. We describe the establishment of a clivus chordoma cell line, MUG-CC1. The cell line is characterized according to its morphology, immunohistochemistry, and growth kinetics. During establishment, cell culture supernatants were collected, and the growth factors HGF, SDF-1, FGF2, and PDGF analyzed using xMAP® technology. A spontaneous lymphoblastoid EBV-positive cell line was also developed and characterized. MUG-CC1 is strongly positive for brachyury, cytokeratin, and S100. The cell line showed gains of the entire chromosomes 7, 8, 12, 13, 16, 18, and 20, and high level gains on chromosomes 1q21–1q24 and 17q21–17q25. During cultivation, there was significant expression of HGF and SDF-1 compared to continuous chordoma cell lines. A new, well-characterized clival chordoma cell line, as well as a non-tumorigenic lymphoblastoid cell line should serve as an in vitro model for the development of potential new treatment strategies for patients suffering from this disease.

Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazáry A, Windhager R, Gattenloehner S & Liegl B 
(2012) Histopathology 60, 999–1003

Management of brain abscesses in children treated for acute lymphoblastic leukemia

Brain abscesses in children with leukemia or other malignancies are rare and potentially fatal. We report on four children who developed brain abscesses during treatment for acute lymphoblastic leukemia (ALL). All patients received multimodal broad‐spectrum antibiotic therapy and liposomal amphotericin‐B in combination with hyperbaric oxygen. First‐line antimicrobial treatment was modified when a causative organism was isolated. All four patients survived, with two patients showing complete resolution of neurological and MRI abnormalities and with two patients still having residual lesions. To date, all patients are in remission with three patients still receiving antileukemic therapy. Brain abscesses can be successfully managed by a multimodality approach even in severely immunocompromised cancer patients. Pediatr Blood Cancer 2009;52:408–411.