Jürgen C. W. Kiwit

Precentral Glioma Location Determines the Displacement of Cortical Hand Representation

OBJECTIVE Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.

Stereotactic Laser Therapy in Cerebral Gliomas

The 1.06 micron Nd:YAG laser and a new fiberoptic delivery system, the Interstitial Thermo-Therapy (ITT) laser fibre, allows stereotactic interstitial irradiation of cerebral tumours. In experimental rat brain studies we found typical laser-tissue effects with a central necrosis and a sharply demarcated oedema towards the normal brain. The size of the lesion depended on the energy and exposure time applied. In a pilot series we treated 5 patients with cerebral gliomas WHO grade II-III in functionally important regions and monitored the therapeutic effects by MR imaging and PET scan. Early post-operative results showed irreversible necrotic changes in the tumour centre and reversible oedematous changes at the tumour margin. Long-term results will show if stereotactic interstitial laser therapy is a useful supplementary method in the treatment of malignant cerebral tumours.

Adjuvant intraarterial chemotherapy with nimustine in the management of world health organization grade IV gliomas of the brain. Experience at the department of neurosurgery of Düsseldorf university

A protocol with postoperative adjuvant intraarterial (ia) chemotherapy using nimustine (ACNU) was followed at the University of Düsseldorf (Federal Republic of Germany) after histologic confirmation of malignant glioma of the brain. The first iaACNU procedure was performed within 10 days of surgery, and immediately before postoperative irradiation. After radiotherapy further iaACNU courses were given. The study population consisted of 35 primarily treated malignant gliomas World Health Organization (WHO) Grade IV, i.e., glioblastomas (NIV). Of these tumors 11 showed early progressive disease (PD) (NIVprimPD), whereas 24 had stable or responsive disease (NIVsd&rd). Seven patients with recurrent malignant gliomas WHO Grade IV (NIV recurrent) were also treated plus six patients with malignant gliomas WHO Grade III (NIII). Experience with 50 treated patients resulted from this study. The median survival time (MST) for the group NIV was 14.2 months; 41.0% of patients were long‐term survivors. The MST for the group NIV primPD was 7.8 months; 9.1% of patients were long‐term survivors. For the group NIVsd&rd a MST of 18.3 months and 66.7% of long‐term survivors were determined. Patients with recurrent tumors on this treatment protocol had an additional MST of 6.1 months. The total MST after first surgery was 16.2 months. The incidence of complications was low. Systemic complications were infrequent or rare. Retinal disturbances were seen in two patients; leukoencephalopathy was not seen in our patients. In 10% of patients cerebral complications were found, which were irreversible in 2% of patients. Complications could not be assigned unequivocally to the nitrosourea. These results compare favorably with what is reported in the literature, demonstrate the potential value of iaACNU in the treatment of malignant gliomas WHO Grade IV, and should encourage the initiation of a randomized clinical trial of adjuvant iaACNU in the therapy of these tumors. The authors propose iaACNU as a valuable approach in the management of primarily diagnosed malignant gliomas WHO Grade IV, but cannot recommend the delay of iaACNU until the recurrence of a brain tumor.

Tomographic studies of rCBF with [99mTc]-HM-PAO SPECT in patients with brain tumors: comparison with C15O2 continuous inhalation technique and PET

In 10 patients with malignant gliomas, the intracerebral distribution of [99mTc]–hexamethylpropyleneamine oxime ([99mTc]–HM-PAO) was studied with single photon emission computed tomography (SPECT) in comparison with C15O2 steady-state inhalation technique to measure cerebral blood flow using positron emission tomography (PET). In all instances, the cerebral [99mTc]–HM-PAO distribution was comparable with the regional pattern of cerebral blood flow (rCBF) observed with PET. This was confirmed by a significant correlation of tumor to cortex and tumor to white matter ratios between these two experimental methods. However, the contrast between high and low activity regions in the SPECT scans was significantly less than that in the PET scans. Contrast enhancement of the SPECT scans was accomplished using a correction formula proposed by Lassen.

Whole-body kinetics and dosimetry ofl-3-[123I]iodo-α-methyltyrosine

The synthetic amino acidl-3-[123I]iodo-α-methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370–550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%±11.5% at 1.5 h p.i., 63.0%±15.7% at 3 h p.i. and 74.6%±9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.

Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies : complete remission of symptoms after intrathecal baclofen administration

A female patient, aged 61 years, who developed a severe immobilizing stiff-person syndrome in conjunction with insulin-dependent diabetes mellitus, is described. In addition to the typical clinical symptoms, diagnosis was proven by the presence of autoantibodies against glutamic acid decarboxylase in serum and cerebrospinal fluid. Symptomatic treatment with continuous intrathecal application of baclofen administered by a subcutaneous pump resulted in rapid clinical improvement so that the patient became ambulatory. Intermittent withdrawal from intrathecal baclofen therapy led to complete remanifestation of stiff-person syndrome within 18 h; after re-introduction of intrathecal therapy stiffness disappeared completely within 48 h. The clinical course has been stable now for over 24 months and stiffness has completely disappeared. The effect of baclofen in this patient is discussed in the light of the suggested pathophysiological mechanisms in stiff-person syndromes.

Osteoclastomas of the petrous bone

Two cases of osteoclastoma of the petrous bone are presented that were clinically taken for tumors of the glomus jugulare. The petrous bone is a very uncommon location for such tumors, and only six cases have been reported in the English literature. The histopathological features as well as the clinical course are described, and the literature is critically reviewed.

Gadolinium-DTPA-enhanced MRI and positron emission tomography of stereotactic laser-induced interstitial thermal therapy in cerebral gliomas

Stereotactic laser-induced interstitial thermal therapy (SLIITT) is a new method for inducing local hyperthermia in cerebral tumours. As pre- and early post-therapeutic evaluations in five patients with cerebral gliomas WHO grade II and III treated by SLIITT we performed ga-dolinium-DTPA-enhanced MRI and positron emission tomography (PET). We found that MRI is a sensitive tool for mapping the spatial and temporal distribution of laser-tissue interactions. PET studies using 2-(18F)fluoro-2-D-de-oxyglucose showed typical changes in glucose metabolism of the glioma. Both investigations seem to reveal irreversible laser effects in the centre of the tumour probably due to a coagulative necrosis and reversible effects at the tumour margin probably caused by reparative processes after SLIITT. It could be demonstrated that laser-tissue interactions progress with time, depending on laser energy and exposure time.

Tomographic studies of rCBF with 99mTc-HM-PAO SPECT in comparison with PET in patients with primary brain tumors.

Abstract99mTc-hexamethyl-propyleneamine-oxime (HM-PAO) was developed as a radiotracer of regional cerebral blood flow (rCBF) with SPECT. THe purpose of this study was to investigate if HM-PAO is able to trace rCBF in primary brain tumors. In 10 patients with glioblastoma grade IV the intracerebral distribution of HM-PAO was studied in comparison with C15O2 steady state inhalation technique and PET for rCBF evaluation. In all instances the cerebral HMPAO distribution was comparable with rCBF pattern as confirmed by a significant correlation of tumor to cortex ratios. The results indicate the clinical usefulness of HMPAO for tracing rCBF in brain tumors.

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI.

Abstract We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated aminoacid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[123I]iodo-α-methyl-l-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures.