Alois Albert Obwegeser

Photodynamic therapy in neurosurgery: a review

Photodynamic therapy (PDT) has been investigated extensively, both experimentally and clinically, as an adjunctive treatment in the neuro-oncological field. It is based on the more selective accumulation of a photosensitizer in malignant than normal tissue with low systemic toxicity. Subsequent light activation induces photo-oxidation, followed by selective tumour destruction via vascular and direct cellular mechanisms. Malignant brain tumours carry a lethal prognosis with a median survival of 15 months despite surgery, radiotherapy and chemotherapy. PDT is therefore a logical therapeutic concept for brain tumours infiltrating into normal brain. In this review, all the available data on patients treated with haematoporphyrin derivative-mediated PDT are critically analysed. Over 310 patients have been reported in the literature suffering from primary or recurrent malignant brain tumours which were treated with PDT following tumour resection in open clinical phase I/II trials. This number includes 58 patients treated at our own institution. Variations in the treatment protocols make evaluation scientifically difficult; however, there is a clear trend of increased median survival after surgical resection and one single photodynamic treatment. PDT is generally well tolerated and side effects consist of moderate increased intracranial pressure and prolonged skin sensitivity to direct sunlight. The current available data indicate that PDT is a safe treatment, which is well tolerated by the patients and yields an improvement in survival of those with malignant brain tumours. Conclusive information can be expected from controlled clinical trials which are currently being designed. The results raise the hope that PDT will be a valuable addition to the armamentarium for the treatment of cerebral malignancies.

Ultrasound-Guided Versus Computed Tomography-Controlled Facet Joint Injections in the Lumbar Spine: A Prospective Randomized Clinical Trial

Background and Objectives: Facet joint injections are widely used for alleviation of back pain. Injections are preferentially performed as fluoroscopy or computed tomography (CT)-controlled interventions. Ultrasound provides real-time monitoring, does not produce ionizing radiation, and is broadly available. Methods: We studied feasibility, accuracy, time-savings, radiation doses, and pain relief of ultrasound-guided facet joint injections versus CT-controlled interventions in a prospective randomized clinical trial. Forty adult patients with chronic low back pain were consecutively enrolled and evenly assigned to an ultrasound or a CT- group. Results: Eighteen subjects from the group randomized to ultrasound were judged to be feasible for this type of approach. In 16 of them the facet joints were clearly visible and all of the associated facet joint injections were performed correctly. The duration of procedure and radiation dose was 14.3 ± 6.6 minutes and 14.2 ± 11.7 mGy˙cm in the ultrasound group, and 22.3 ± 6.3 minutes and 364.4 ± 213.7 mGy˙cm in the CT group. Both groups showed a benefit from facet joint injections. Conclusions: The ultrasound approach to the facet joints in the lumbar spine is feasible with minimal risks in a large majority of patients and results in a significant reduction of procedure duration and radiation dose.

Ultrasound Guidance for Facet Joint Injections in the Lumbar Spine: A Computed Tomography-controlled Feasibility Study

We conducted this study to develop an ultrasound-guided approach for facet joint injections of the lumbar spine. Five zygapophyseal joints (L1-S1) on each side of 5 embalmed cadavers were examined by ultrasound for a total of 50 examinations. The joint space was demonstrated under ultrasound guidance. The midpoint of the joint space, defined as the middle of its cranio-caudal extension on its dorsal surface, was taken as a reference point, and its position was computed from its depth and lateral distance from the spinous process. Forty-two of 50 approaches could be clearly visualized. Subsequently, these distances were compared to those obtained by computed tomography (CT). To assess the efficacy of ultrasound in the needle placement, all lumbar facet joints were approached in one embalmed cadaver. The exact placement of the needle tips was again evaluated by CT. Ultrasound and CT measurements showed the same mean depth and lateral distance to the reference point, 3.15 ± 0.5 cm and 1.9 ± 0.6 cm, respectively. Pearson’s coefficient of correlation was 0.86 (P < 0.0001) between ultrasound and CT. All 10 needle tips were within the joint space during simulated facet joint injections. We conclude that ultrasound guidance might be a useful adjunct for facet joint injections in the lumbar spine.

Thalamic stimulation for the treatment of midline tremors in essential tremor patients

Article abstract The authors prospectively collected unblinded data from 27 consecutive patients following thalamic stimulation. A significant reduction of midline tremor was achieved after unilateral surgery, but a staged contralateral surgery had an additional effect. A subgroup analysis showed significant beneficial effects for head, voice, tongue, and face tremor. The most frequent reversible side effects were disequilibrium, dysarthria, and paresthesias. We observed more pulse generator adjustments for speech problems in the bilaterally implanted group.

Bilateral thalamic deep brain stimulation: midline tremor control

Objectives: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor. Design: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter. Methods: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor. The tremor rating scale was the primary outcome measure. Results: Midline tremor showed significant improvement with stimulation “on” at nearly every postoperative interval when compared with stimulation “off” and with baseline tremor. Bilateral stimulation was associated with a significant incremental improvement in midline tremor control compared with unilateral stimulation: average “stimulation on” percentage change in midline tremor from the unilateral to bilateral period was 81%. Head and voice tremor showed the most consistent improvement. Among those requiring a change in stimulation parameters because of side effects, dysarthria, disequilibrium, motor disturbances, and paraesthesiae were the most common. Dysarthria was more common with bilateral (n = 6; 27%) than with unilateral (n = 0) stimulation. Stimulation parameters remained largely unchanged after the first three months. Nine of 44 leads placed (20%) required subsequent repositioning or replacement. Conclusions: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control.

Real-time sonographic imaging for periradicular injections in the lumbar spine: a sonographic anatomic study of a new technique.

We conducted this study to develop a sonographically guided approach to the spinal nerve of the lumbar spine and to assess its feasibility and accuracy by means of computed tomography (CT).

Ultrasound-guided facet joint injections in the middle to lower cervical spine: a CT-controlled sonoanatomic study.

ObjectivesThe aim of this study was to investigate the efficacy of ultrasound as a guiding tool for simulated cervical facet joint injections in cadavers. MethodsA total of 40 ultrasound examinations at 5 levels (C6-7 to C2-3) were performed on 4 embalmed cadavers. The zygapophyseal joints were located with ultrasound. First, the transverse processes of C6 and C7 were established and the facet joint of C6-7 was demonstrated. The midpoint of this joint space, defined as the middle of its cranio-caudal extension on its lateral surface, was taken as a reference point. Ipsilateral distances (A, B, C, and D) between this point and each one of the 4 facet joints of the cervical spine up to the facet joints C2-3 were then computed. Subsequently, coronal computed tomography (CT) scans were taken to verify these distances. In a second experiment, a spinal needle was advanced under ultrasound guidance to the zygapophyseal joints from C2-3 to C6-7 on both sides of 1 cadaver. The exact placement of the needle tips was again verified by CT. ResultsIn 4 attempts, a depiction of the joint space was not possible. Ultrasound and CT provided the same mean measurements of 1.2±0.2 cm, 2.0±0.3 cm, 3.0±0.2, and 4.0±0.5 cm for distances A, B, C, and D, respectively. All 10 needle tips were located in the joint space during simulated facet joint injections, as also verified by CT. DiscussionThis preclinical study suggests that ultrasound is a useful guiding tool for facet joint injections in the cervical spine.

Quantitative and qualitative outcome measures after thalamic deep brain stimulation to treat disabling tremors.

OBJECTIVEWe studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson’s disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed. METHODSForty-one patients with essential tremor or Parkinson’s disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed. RESULTSQualitative measurements demonstrated significant improvement of contralateral upper-limb (P < 0.001), lower-limb (P < 0.01), and midline (P < 0.001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < 0.01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < 0.001) and postural (P < 0.01) tremors and ipsilateral postural tremor (P < 0.05). Activities of daily living improved after unilateral surgery (P < 0.001) and additionally after bilateral surgery (P < 0.05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants. CONCLUSIONUnilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible.

Ultrasound-guided periradicular injections in the middle to lower cervical spine : An imaging study of a new approach

Background and Objectives The objective of this study was to show the efficacy of ultrasound in facilitating the performance of a simulated cervical periradicular injection in cadavers. Methods A total of 40 ultrasound-guided examinations at 4 levels (C3 to C7) were performed on 4 embalmed cadavers. The cervical spinal nerves were located with ultrasound. First, the transverse process of each level was taken as a sonoanatomic landmark. The most lateral aspect of the transverse process of the seventh cervical vertebra was then established as the reference point. Ipsilateral distances (A, B, C, and D) between this point and each one of the transverse processes of the cervical spine up to the third vertebra were then computed. Subsequently, coronal computed tomography (CT) scans were taken to verify these distances. In a second part, a spinal needle was advanced under ultrasound guidance to the spinal nerves C5 to C8 on both sides of one cadaver. The exact placement of the needle tips was checked by CT. Results The transverse processes were identified in all cadavers. In 5 attempts, a depiction of the spinal nerves was not possible. Ultrasound and CT provided the same mean measurements of 1.1 cm, 2.1 cm, 3.1 cm, and 4.1 cm for distances A, B, C, and D, respectively. All 8 needle tips were placed within 5 mm dorsal to the spinal nerve and less than 5 mm away from the posterior tubercle of each levels transverse process, as also verified by CT. Conclusions This preclinical study suggests that ultrasound is a useful guiding tool for periradicular injections in the cervical spine.

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression

Abstract Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum. Samples were collected from 14 patients with primary brain tumors of various histology (six glioblastomas, one protoplasmatic astrocytoma, two pilocytic astrocytomas, one ependymoma, one meningioma, and three craniopharyngiomas) and two patients with solitary cystic brain metastases from adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic lung cancer the concentration of VEGF in serum and cyst fluid was determined during disease progression. During 60 days of follow-up VEGF concentrations in the cyst fluid collected by puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive VEGF is produced at the tumor site and abundantly released into the cyst fluid of primary and metastatic brain tumors. Interestingly, this abundant local release is not reflected in serum VEGF levels, even in the case of very high VEGF concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the formation of tumor cysts in brain tumors and correlates with local disease progression.