[Intrathecal baclofen therapy. Overdose during replacement of a medication pump]. / Intrathekale Baclofentherapie. Uberdosierung beim Wechsel der Medikamentenpumpe.

This case report reviews the anesthesiological complications of intrathecal baclofen (ITB) therapy. An 11-year-old boy with spasticity and apallic syndrome needed general anesthesia for exchange of a baclofen pump but 2 h later he became increasingly hypothermic, hypotonic with bradycardy and dyspnea. The cause was an intra-operative bolus of ITB. Reduction of the baclofen administration rate caused disappearance of all symptoms without any residual effects. The ITB is an increasingly used therapeutic option for multiple sclerosis and cerebral palsy. Therefore, emergency personal and anesthesiologists must be aware of the possible side effects of this medication.

Sectioning of filum terminale externum using a rigid endoscope through the sacral hiatus. Cadaver study.

AIM: Tethered cord syndrome (TCS) is a stretch-induced functional disorder of the spinal cord, which is directly related to filum fixation. Classic surgical approaches to the filum involve open surgery and include varying amounts of spinal bone removal. In an effort to reduce the morbidity and mortality of these procedures, the authors explored a less invasive method. They evaluated the ability, safety and feasibility for endoscopic sectioning of the filum terminale externum by performing upward orientated navigation in the extradural sacral spinal canal through the sacral hiatus using a rigid endoscope. METHODS: Four adult, phenol-formalin embalmed cadavers were used for endoscopic section of the filum terminale externum at the tip of thecal sac. After preparing the anatomical area of sacral hiatus, a rigid endoscope (Storz, of 3.8 mm external diameter with two working channels, of 1 mm each, one for suction-irrigation and one as working) was inserted into the extradural sacral spinal canal and the filum terminale externum was identified and cut easily at the distal end of thecal sac at the level of S2. In all cases, it was possible to manipulate the rigid endoscope and inspect the full length of the extradural sacral spinal canal, especially at the S1-S2 level. RESULTS: The results indicate that the tested transhiatal approach for upward orientated extradural endoscopy represents a minimally invasive procedure that provides an appropriate and feasible route to the extradural sacral spinal canal. CONCLUSION: Such approach is an attractive alternative for filum terminale externum sectioning in cases where tethered cord syndrome is not accompanied by any other pathology. Moreover if filum terminale internum sectiong is indicated, it can be performed in second stage.

Deep brain stimulation for Parkinson's disease.

Indications for the treatment of Parkinson's disease (PD) with deep brain stimulation (DBS) are severe, therapy refractory tremor and complications of long-term levodopa uptake. Since its first application DBS has become a standard therapy for these patients. Theoretically, the ventrolateral part of the internal pallidum (GPI) or the subthalamic nucleus (STN) are suitable targets in order to treat all cardinal symptoms of patients in an advanced stage of PD stereotactically. Although clinical efficacy of both GPI or STN stimulation is obviously comparable, it has become widely accepted to prefer STN over GPI DBS. If PD-associated, medically intractable tremor is the most disabling symptom, stimulation of the ventrolateral motor thalamus can be an alternative. Anatomical targets for DBS are small and located in critical brain areas. Furthermore, this type of surgery is highly elective. As a consequence, high resolution multiplanar imaging and adequate treatment planning software are indispensable prerequisites for DBS surgery. Currently, commercially available impulse generators deliver a permanent high frequency periodic pulse train stimulation that interacts rather unspecifically with the firing pattern of both normal and pathological neurons. Prospectively, the development of more specific stimulation paradigms may help to improve the efficacy of this treatment modality.

Intrathecal opioids for intractable pain syndromes.

For more than 20 years intrathecal opioid application with implantable pumps is an option for selected patients with malignant as well as non-malignant pain. In general, most types of pain should be treatable by opioid medication. However, the associated systemic side-effects such as nausea, vomiting, constipation or the risk of suppression of the central nervous system hinder the application of oral or intravenous opioid therapy as a sole, widely applicable treatment. Causes of non-malignant pain that may represent an indication for intrathecal drug-delivery systems include: failed back syndrome, neuropathic pain, axial spinal pain, complex regional pain syndrome, diffuse pain, brachial plexitis, central pain, failed spinal cord stimulation (SCS) therapy, arachnoiditis, poststroke pain, spinal cord injury pain and peripheral neuropathy. Due to the proximity to the receptor sites, the therapeutic effect of intrathecal drug application lasts longer and the rate of systemic side effects is reduced. Before definitive pump implantation, the therapeutic effect of intrathecal opioid therapy is tested with an external pump. If there is no clear and satisfactory effect in this trial application, pump implantation is not indicated. In our patients, with a follow-up exceeding 3 years, the reduction of non-malignant pain (assessed with the Visual Analogue Scale, VAS) was good or excellent (pain decrease >50%) in 71.3% of the patients, fair (VAS 5-6) in 19.8% and poor (VAS 7-10) in 8.9%. After 3 years of continuous treatment, we observed catheter-related technical problems (catheter dislocation, obstruction, kinking, disconnection or rupture) in 17 of 165 patients. Pump malfunctions were very rare (8 of 165 cases) and limited to older pump types. Reversible, specific drug-related side effects of long-term therapy with intrathecal pumps developed in 32 of the 165 patients. In our series, the mean serum/cerebrospinal fluid (CSF) concentration ratio for morphine was 1/3000, which explains the low rate of systemic side effects. Local diffusion difficulties in CSF cause an uneven distribution of morphine in CSF. Therefore the clinical effect is markedly influenced by the position of the catheter tip, a fact that should be kept in mind during catheter implantation. Intrathecal drug application is cost effective and can significantly improve the quality of life in selected patients. An intensive training in this method and awareness of its specific complications is necessary for everyone to participate in the consulting and implanting team. Pumps for chronic intrathecal opioid application should only be implanted in specialized centers.

Neurosurgical pain therapy with epidural spinal cord stimulation (SCS).

Neurosurgical therapy for intractable pain with epidural implantable electrodes has become a widely used and efficient alternative when conservative or less invasive therapies are no longer effective. A complete interdisciplinary work-up is required before considering a patient as a candidate for a spinal cord stimulation (SCS) device. In more than 1300 patients we implanted an SCS device in our clinic; more than 52% reported a significant (>50%) long-term improvement for more than 3 years and a significant reduction in their analgesic drugs. Although placement of the electrode and implantation of the stimulator are technically easy to perform, they do carry a risk of potentially debilitating complications such as meningitis or component migration. Hence. SCS therapy should only be performed in specialized centers. In peripheral vascular disease (PVD) and angina, the initial results are very promising, but the long-term efficacy has to be proven by multicenter studies.

Intrathecal antispastic drug application with implantable pumps: results of a 10 year follow-up study.

Since 1986, more than 300 patients received an intrathecal baclofen (ITB) pump for the treatment of severe spasticity. Chronic ITB administration is a safe and effective method, which significantly decreases pathologically exaggerated muscle tone and improves the quality of life in most patients. This therapy is indicated in severe spasticity of cerebral or spinal origin that is unresponsive to oral antispastic medications. It is also useful in patients who may experience intolerable side effects when they receive orally effective baclofen doses. The therapeutic dose required to treat spasticity of cerebral origin is about three times higher than in spasticity of spinal origin. In carefully selected patients who suffer from spasticity, pump implantation is a cost-effective treatment which improves their quality of life. In our series with a follow-up period of 10 years, the ITB dose remained constant and no development of tolerance was observed in most patients. Destructive procedures such as myelotomy are no longer performed in our department in order to treat spasticity.

Endoscopic anatomy of the thecal sac using a flexible steerable endoscope.

In this study the ability for upward-orientated endoscopic visualization of thecal subarachnoid space using a flexible steerable endoscope was evaluated in order to compare endoscopic anatomical findings with the already known macroscopic ones of the incontained structures and to test the approach for clinical employment. For this purpose, four adult phenol-formalin embalmed cadavers were used and the approach selected was through a laminectomy window at the S1-S2 level. The dura mater was opened and a flexible steerable endoscope (Storz, of 2.8 mm external diameter with one working channel) was inserted subarachnoidally for upward-orientated observation of the content of thecal sac. By using this approach filum terminale, lower lumbar, sacral and coccygeal nerve rootlets were identified and observed in detail. By moving the endoscope even more upwards, inspection of the upper part of the thecal subarachnoid space and conus medullaris was also possible. The findings collected from the study indicate that this approach for upward-orientated intradural subarachnoid endoscopy gives an appropriate working and inspecting window to the lower, as well as to the upper part of the thecal subarachnoid space and even of the conus medullaris. Furthermore, inspection and identification of lower lumbar, sacral and coccygeal nerve rootlets is possible and efficient and the endoscopic anatomical observations coincide with the already known gross-anatomical ones.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre.

OBJECTIVE: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. METHODS: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). RESULTS: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. CONCLUSIONS: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients' prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.

Drug adverse events and system complications of intrathecal opioid delivery for pain: origins, detection, manifestations, and management.

Intrathecal drug delivery is effective for the treatment of cancer and nonmalignant pain in patients who do not respond well to oral opioids, in patients who cannot tolerate the side effects associated with opioids, or in patients who show a large, permanent increase in dosage. Although intrathecal drug delivery is associated with pharmacological side effects and complications, its benefits far outweigh its risks. There are three main categories of potential adverse events associated with intrathecal drug delivery: pharmacologic side effects, surgical complications, and device-related complications. Prevention, early recognition, and prompt management of adverse events will optimize patient outcomes. Many adverse events either resolve on their own or can be managed with dosage or device adjustment. More serious complications may require surgical intervention or discontinuation of therapy. This paper will provide an overview of adverse events and complications, their origins, detection, manifestations, and management.

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Pressor and depressor responses in thermocoagulation of the trigeminal ganglion.

We have undertaken a retrospective analysis in 126 patients with trigeminal neuralgia on which a free-hand percutaneous thermocoagulation of the Gasserian ganglion was performed in our department. We focused on the occurrence of intraoperative vagal reactions, i.e. significant bradycardia and changes in blood pressure during the course of the procedure. Operative and anaesthetic records of patients who underwent the procedure were evaluated and correlated with clinical data from the patient's history. We observed the occurrence of vagal reactions i.e. significant bradycardia (< 50/min) or syncope in 20% of patients (p < 0.0002) during or immediately after penetration of the foramen ovale. No correlation between the operated side and the occurrence of vagal reactions was found. A significant rise in blood pressure levels (about 180 mmHg systolic) was observed in 36% of patients during thermocoagulation. We concluded that painful stimuli arising from lesioning in the course of the trigeminal nerve reach the mid-brain and may irritate the dorsal nucleus of the vagus nerve resulting in significant bradycardia or cardiac synode. To prevent haemodynamic deterioration i.v. atropine (0.5-2 mg) should be available when advancing the needle, while anti-hypertensive medication (Esmolol) may be needed during coagulation.

Intrathecal chemotherapy with ACNU for meningeal gliomatosis.

ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour.

Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model.

Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso urea hydrochloride) had a remarkable chemotherapeutic effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats with meningeal gliomatosis induced by an intracisternal inoculation of rat C6 glioma cells. The median survival time of the rats treated with a single dose of intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as compared with that of the control animals. Meningeal gliomatosis rat models treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of the animals. These findings suggest that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of meningeal gliomatosis, whereas intravenous chemotherapy with a high dose of ACNU is always ineffective.

Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo.

Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.

Experience with spinal cord stimulation (SCS) in the management of chronic pain in a traumatic transverse lesion syndrome.

Epidural electrical stimulation of the spinal cord by means of percutaneously implanted electrodes was successfully used in cases of traumatic paraplegia with chronic pain, more particularly if vegetative components predominated. Out of seven patients treated in our clinic six reported a good or very good outcome of the stimulation over follow-up periods up to six years. On account of the good effect on chronic pain the use of this stimulation procedure is indicated and justified before considering any destructive operative measures.

[Blockade of the left stellate ganglion using a drug reservoir pump. A new treatment method in the QT syndrome]. / Blockade des linken Ganglion stellatum mittels Medikamentenpumpe. Eine neue Behandlungsmethode bei QT-Syndrom.

In patients with long QT syndrome (LQTS) the therapy of first choice is the administration of propranolol (2-4 mg/kg of body weight daily). If not effective alone, a combination of propranolol and phenytoin (200 mg daily) has proved to be effective. Nevertheless, in about 7% of cases medical therapy failed to prevent serious arrhythmic events. A 28-year-old woman suffered tachyarrhythmic episodes despite medical treatment. After additional pharmacological blockade of the left stellate ganglion, using an implantable pump catheter system (Secor) a stable heart rhythm could be achieved. No more syncopes were reported in this patient. In the case of failing medical therapy, the implantation of a pump catheter system could be an alternative method to surgical left ganglion stellectomy.

Application of SCS for movement disorders and spasticity.

20 patients with movement disorders and spasticity were treated with SCS to decrease tonus and improve impaired motor function. 12 patients with multiple sclerosis had gait disorders and slight up to considerable increase in tonus. We observed quantitative changes in diminution of spasticity, voluntary motor function, bladder function, lessening of ataxia and pain relief. During a follow-up of up to 4 years no deterioration in the patients' condition could be observed. 11 patients reported a more fluent gait in 6 cases accompanied by a decrease in tonus. Increase in tonus and deterioration of gait pattern were observed after break down of the stimulation. Although the indications for electrostimulation still remains uncertain in some cases with definite diagnosis without any progressive character of the disease and without severe neurological disturbances improvement can be obtained.

[Magnetic resonance tomography of spinal masses]. / Magnetische Resonanztomographie (MR) bei spinalen Raumforderungen.

We examined 22 intramedullary, 17 intradural extramedullary and 20 extradural lesions, with direct involvement of the spinal cord by magnetic resonance tomography, using surface coils and 5 mm., or narrower continuous sections. Spinecho pulse sequences are suitable for multi-slice examinations. T.1-weighted examinations are suitable for demonstrating the syrinx in syringomyelia, in all other circumstances T1 and T2 sequences are essential. Gd-DTPA is unnecessary. The results of these recommendations are illustrated.