RESUMEN

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

Asunto(s)

Asunto(s)

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. The allergic clinical symptoms are variable and unpredictable. The aim of this study was to identify the characteristics of hypersensitivity reactions and to assess the value of skin tests for platinum salts and pemetrexed in the treatment of patients with non-small cell lung cancers or malignant pleural mesothelioma. METHODS: A single-centre retrospective study was performed for 2 years. Patients treated with the drugs of interest for an advanced or metastatic non-small cell lung cancers or malignant pleural mesothelioma and who experienced hypersensitivity reactions symptoms were eligible for this study. Clinical symptoms of hypersensitivity reactions, population characteristics and administered chemotherapy regimens were identified. RESULTS: The hypersensitivity reactions frequency was rare (1.2%) and concerned 17 patients in our study. Typical clinical features of immediate hypersensitivity reactions associated with treatment were observed for nine patients (anaphylactic reactions for three cases, angioedema and hypotension associated with asthenia and heat in one case, respectively, and other cutaneous symptoms in the remaining four cases). Skin tests were positive in three patients, but only for platinum salts. The outcome after reintroduction of a negatively tested platinum salt allowed us to calculate a negative predictive value for platinum salt skin tests of 100%. For pemetrexed, skin tests were negative for all patients. WHAT IS NEW AND CONCLUSION: Skin tests could be used to diagnose hypersensitivity reactions with platinum salts or to evaluate the possibility of cross-reactions between two platinum salts. A negative skin test may predict with reasonable reliability the absence of future hypersensitivity reactions in case of reintroduction of drug infusion. Because the IgE-mediated mechanism has never been demonstrated for pemetrexed, skin tests are not valid and have no diagnostic value for this molecule. Because hypersensitivity reactions are potentially fatal adverse events, we recommend that patients who experience a hypersensitivity reactions onset should be monitored closely and clinicians must be aware of hypersensitivity reaction signs.

Asunto(s)

RESUMEN

BACKGROUND: Deep brain stimulation (DBS) is an established therapy for movement disorders. It is currently under investigation in neuropsychiatric disorders. Neurophobia is a common phenomenon that might have a negative impact in medical education. Little is known about medical students' knowledge about DBS when they enter university and what they learn about it during their medical formation. METHODS: A 10-item questionnaire was designed. Questions addressed indications for DBS, costs of DBS, complications, the percentage of Parkinson disease (PD) patients who might profit from DBS, etc. Students at Hannover Medical School were asked to complete the questionnaire in the preclinical study period and in the last year of the study. RESULTS: Comparing the "early group" (204 students) and the "advanced group" (162 students), there was a significant gain of knowledge. More common disorders such as PD and tremor were known to be indications for DBS. Knowledge about the impact of DBS on specific symptoms in PD and about DBS targets was limited in both groups. CONCLUSIONS: DBS is partly known among medical students in the preclinical phase with a gain of knowledge during further study. Future studies on this topic addressing general practitioners as neurologists are needed to better understand why knowledge on DBS is still limited.

Asunto(s)

RESUMEN

BACKGROUND: Trigeminal neuralgia (TN) is characterized by paroxysmal pain attacks affecting the somatosensory distributions of the trigeminal nerve. It is thought to be associated with a neurovascular conflict most frequently, but pathomechanisms have not been fully elucidated. In general, no sensory deficit is found in routine clinical examination. There is limited data available, however, showing subtle subclinical sensory deficits upon extensive testing. OBJECTIVE: We used quantitative sensory testing (QST) to detect abnormalities in sensory processing in patients with TN by comparing the affected and non-affected nerve branches with their contralateral counterparts and by comparing the results of the patients with those of controls. STUDY DESIGN: Observational study. SETTING: University Hospital, Departments of Neurosurgery, Institute for Cognitive and Clinical Neuroscience. METHODS: QST was conducted on 48 patients with idiopathic TN and 27 controls matched for age and gender using the standardized protocol of the German Neuropathic Pain Network. Stimulations were performed bilaterally in the distribution of the trigeminal branches. The patients had no prior invasive treatment, and medications at the time of examination were noted. RESULTS: In patients with TN deficits in warm and cold sensory detection thresholds in the affected and also the non-affected nerve branches were found. Tactile sensation thresholds were elevated in the involved nerve branches compared to the contralateral side. LIMITATIONS: More data are needed on the correlation of such findings with the length of history of TN and with changes of the morphology of the trigeminal nerve. CONCLUSIONS: QST shows subtle sensory abnormalities in patients with TN despite not being detected in routine clinical examination. Our data may provide a basis for further research on the development of TN and also on improvement after treatment. KEY WORDS: Quantitative sensory testing, trigeminal neuralgia, facial pain, neuropathic pain, microvascular decompression, cranial nerve.

Asunto(s)

RESUMEN

BACKGROUND: Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. OBJECTIVE: In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. STUDY DESIGN: Observational study. SETTING: University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. METHODS: Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. RESULTS: Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. LIMITATIONS: The exact time span that SCS continues to have an effect is not known. However, due to patient discomfort discontinuation of SCS therapy was not prolonged over a 24 hour period. Further limitations were the low number of patients who agreed to discontinue SCS therapy for research purposes. CONCLUSIONS: Long-term SCS for treatment of neuropathic pain influenced both pain thresholds and cortical signalling. Source localization of P1 suggests involvement of regions involved in cognitive/associative processing of pain.

Asunto(s)

RESUMEN

Altered processing in the basal ganglia has been described both in dystonia and Tourette's syndrome (TS). Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become a recognized treatment for dystonia and has been used successfully to alleviate tics in TS. This study evaluates possible differences of GPi linear and nonlinear neuronal discharge characteristics between patients with dystonia and TS. Nine patients with primary dystonia and six patients with TS were studied during functional stereotactic neurosurgical operations for implantation of DBS electrodes under general anesthesia. Six patients with primary dystonia under local anesthesia served as non-anesthetized controls. Single-unit activity recordings in the GPi were obtained during routine microelectrode recording and mapping to delineate nuclear borders and to identify the sensorimotor subregions. Anesthesia profoundly decreased neuronal activity in patients with dystonia. Dystonia patients showed marginally higher mean firing rates in the GPi compared to TS patients (P = 0.06). Although the average total number of bursts and the mean peak frequency in bursts did not differ between groups, the mean spikes in bursts were higher in dystonia patients (P < 0.05). Nonlinear time series analysis metrics, measured as complexity of Lempel-Ziv and maximum approximate entropy, revealed higher randomness in TS compared to dystonia patients (P < 0.05). The percentage of oscillating neurons in spike trains was higher in dystonia compared to TS (P < 0.05). Our data provide evidence for differences of the neuronal dynamic complexity, randomness and oscillatory modulation of spike trains in the GPi between dystonia and TS. Such differences, although subtle, might contribute to the specific clinical phenomenology secondary to disordered neuronal basal ganglia processing.

Asunto(s)

RESUMEN

BACKGROUND: In Parkinson's disease (PD) dyskinesias appear after long-term dopaminergic treatment. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) is a well-established treatment option for both PD symptoms and complications of medication. OBJECTIVE: To elucidate physiological mechanisms of the effect of DBS on levodopa-induced dyskinesias (LID) we investigated both DBS in the GPi and the centromedian-parafascicular complex (CM-Pf), which are part of an internal basal ganglia loop connecting with the dorsolateral striatum. In particular, we focused on changes of oscillatory activity in the dorsolateral striatum, which also presents the entrance region of the basal ganglia (BG). METHODS: 6-Hydroxydopamine (6-OHDA) hemiparkinsonian (HP) rats and 6-OHDA lesioned HP rats with LID (HP-LID) were used to compare the effect of DBS in the entopeduncular nucleus (EPN, the equivalent to the human GPi) and the thalamic parafascicular nucleus (Pf, the equivalent of the human CM-Pf) on dyskinesias and neuronal oscillatory activity of selected frequency bands in the dorsolateral striatum on and off levodopa. RESULTS: In HP-LID rats the relative beta and gamma power was lower, while relative theta power was higher as compared to HP rats. Chronic DBS of either the EPN or the Pf improved dyskinesia scores in HP-LID rats, and no differences in oscillatory activity were observed between groups. CONCLUSIONS: Stimulation of the Pf has a specific impact on dyskinesias, which is similar to that found after EPN stimulation, and which is accompanied by changes of oscillatory activity.

Asunto(s)

RESUMEN

We report on a 66-year-old woman with segmental dystonia treated with chronic bilateral deep brain stimulation of the globus pallidus internus, in whom accidental high-voltage, high-frequency stimulation induced an episode of transient global amnesia (TGA) via an electrode contact which was misplaced in the right hippocampus. A possible mechanism underlying this TGA episode may have been the inhibition of local neuronal activity or fiber activation by high current density via direct electrical stimulation of hippocampal structures. While a unifying etiology of TGA has not been proven so far, our case demonstrates a possible link between focal electrical stimulation of hippocampal structures and the full clinical picture of the syndrome.

Asunto(s)

RESUMEN

BACKGROUND: Freezing of gait is a disabling feature of Parkinson's disease, and so far no established treatment exists. Deep brain stimulation of the pedunculopontine area has been proposed to treat refractory gait disorders, yet data on measurable effects, especially in combination with stimulation of other targets, are scarce. METHODS: Acute effects of either low frequency pedunculopontine stimulation or high frequency stimulation of the posteroventral lateral globus pallidus internus and a combination of both in a 66-year-old man with advanced Parkinson's disease were assessed. Four weeks after the intervention, the gait was examined with patient blinded in each condition using computerized gait analysis. RESULTS: Isolated pedunculopontine or pallidal stimulation had a mild impact on gait ignition and freezing of gait, but combined stimulation had a marked effect. CONCLUSIONS: Combined multifocal stimulation may be a promising option for gait ignition and freezing of gait in advanced Parkinson's disease.

Asunto(s)

RESUMEN

BACKGROUND: Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. Severe long-term complications are rare. Only recently secondary mass lesions associated with chronic stimulation were noted to occur. OBJECTIVES: To report the rare occurrence of cervical myelopathy secondary to an epidural cervical spinal mass after chronic cervical SCS. METHODS: Implantation of a paddle electrode at C2-C4 for chronic neuropathic pain resulted in improvement of pain for several years but it lost its efficacy after 8 years. Myelography and postmyelographic CT detected an epidural mass surrounding the electrode and compressing the spinal cord when cervical myelopathy had developed 17 years after electrode implantation. RESULTS: The mass which consisted of dense fibrous scar tissue was removed via hemilaminectomy. At postoperative follow-up at 8 months there was no further progression of gait disorder. CONCLUSION: Long-term cervical SCS in a rare case may lead to fibrous epidural mass lesions which may not only cause loss of efficacy but which may also result in new neurological deficits.

Asunto(s)

RESUMEN

Pneumocephalus may occur after intracranial surgery and is most often asymptomatic. It is usually associated with posterior fossa surgery. Here, we present a 56-year-old man who developed akinetic mutism and parkinsonism caused by subdural and intraventricular tension pneumocephalus associated with decompression of a chronic subdural hygroma. As an emergency treatment, air was exchanged with saline via the drainage, which then was removed and a subduro-peritoneal shunt was implanted. The condition described here requires immediate attention and appropriate treatment.

Asunto(s)

RESUMEN

Segmental thoracic neuropathic pain (NeuP) remains particularly difficult to treat. Sensory ganglionectomy was reported to alleviate NeuP. The experience with thoracic ganglionectomy, however, is very limited. Here, we report the results of a prospective pilot study in patients with incapacitating segmental thoracic NeuP treated by selective ganglionectomy. Seven patients were included suffering from refractory NeuP scoring 8 or more on a visual analogue scale (VAS). Every patient had test anaesthesia prior to surgery yielding more than 50% pain relief. The spinal ganglion was excised completely via an extraforaminal approach. Mean preoperative VAS scores were 9.1 (maximum pain); 5.4 (minimum pain); 7.9 (pain on average); 6.9 (pain at the time of presentation); and 7.4 (allodynia). Early post-operatively, there was a marked improvement of mean scores: 1.7; 0.7; 1.2; 1.0; and 0.7, respectively. One patient developed a mild transient hemihypaesthesia. In three patients, substantial pain occurred in a formerly unaffected dermatome within 1 year. Two of these patients had significant pain relief by a second operation. At the time of last follow-up at a mean of 24 months after the first procedure, mean VAS scores were 6.3; 2.1; 4.3; 4.0; and 1.3. Overall, medication was reduced. The patients rated their outcome as excellent (1), good (2), fair (2) and nil (2) with best improvement for allodynia. Selective thoracic ganglionectomy is a safe and partially effective procedure in selected patients albeit there may be partial recurrence of pain. Recurrent pain may affect dermatomes that were not involved initially.

Asunto(s)

RESUMEN

Misplacement of the ventricular catheters of shunt systems may result in shunt dysfunction or a variety of neurological symptoms. Bilateral fourth nerve palsy has not been reported thus far after shunting. Here, we describe the occurrence of this unusual neurological deficit in a patient who underwent shunting for normal pressure hydrocephalus, and demonstrate its pathoanatomical correlate.

Asunto(s)

RESUMEN

OBJECTIVES: Stimulation-induced hypokinetic gait disorders with freezing of gait (FOG) have been reported only recently as adverse effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with dystonia. The aim of this work was to determine the frequency and the nature of this GPi-DBS-induced phenomenon. METHODS: We retrospectively screened our database of patients with dystonia who underwent DBS. Patients with focal, segmental, or generalized dystonia of primary or tardive origin and no gait disorder due to lower limb dystonia before DBS, bilateral pallidal stimulation, and a follow-up for more than 6 months were included. Reports of adverse events were analyzed, and gait abnormalities were scored by comparing preoperative and postoperative video recordings using Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 3.10 (gait) and 3.11 (FOG). To assess the role of GPi-DBS in gait abnormalities, DBS was paused for 24 hours. Gait and FOG were assessed 30 minutes, 2 hours, and 24 hours after restarting DBS. Finally, a standardized adjustment algorithm was performed trying to eliminate the gait disorder. RESULTS: Of a collective of 71 patients with dystonia, 6 presented with a new gait disorder (8.5%; 2 men, 4 women, mean age 61.3 years [48-69 years], 2 craniocervical, 1 DYT-1 segmental, 1 truncal, 2 tardive dystonia). GPi-DBS improved Burke-Fahn-Marsden Dystonia Rating Scale motor score by 54% and disability score by 52%. MDS-UPDRS item 3.10 worsened from 0.5 (±0.8) to 2.0 (±0.9) and item 3.11 from 0 to 2.5 (±0.5). The gait disorder displayed shuffling steps and difficulties with gait initiation and turning. Increasing voltages improved dystonia but triggered FOG, sometimes worsening over a period of a few hours. It vanished within minutes after ceasing DBS. Electrode misplacement was ruled out. In all but one patient, no optimal configuration was found despite extensive testing of settings (monopolar, bipolar, pulse width 60-210 µs, frequency 60-180 Hz). Nevertheless, a compromise between optimal stimulation for dystonia and eliciting FOG was achieved in each case. CONCLUSIONS: A hypokinetic gait disorder with FOG can be a complication of GPi-DBS.

Asunto(s)

RESUMEN

The hypothalamus supports basic motivational behaviours such as mating and feeding. Recording directly from the posterior inferior hypothalamus in a male patient receiving a deep brain stimulation (DBS) electrode for the alleviation of cluster headache, we tested the hypothalamic response to different classes of motivational stimuli (sexually relevant: pictures of dressed and undressed women; pictures of food) and pictures of common objects as control. Averaged local field potentials (LFP) to sexually relevant stimuli were characterized by a biphasic significantly enhanced response (relative to objects; bootstrapping statistics) with a first phase starting at around 200 ms and a second phase peaking at around 600 ms. Sexually relevant stimuli also showed a greatly enhanced positivity relative to other stimulus classes in surface event-related potentials in a group of 11 male control participants. It is suggested that the hypothalamus is involved in the recruitment of attentional resources by sexually relevant stimuli reflected in this surface positivity. In a second session, the response to food stimuli relative to objects was tested in two states: after fasting for 14 h, LFPs to food and object stimuli showed significant differences in between 300 and 850 ms, which disappeared after a full high-calorie meal, thus replicating classic studies in monkeys [Rolls et al., Brain Res (1976) 111:53-66]. The current data are the first to demonstrate hypothalamic responses to the sight of motivational stimuli in man and thus shows that recording from DBS electrodes might provide important information about the cognitive functions of subcortical structures.

Asunto(s)

RESUMEN

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short-term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long-term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke-Fahn-Marsden Dystonia Rating Scale showed a mean improvement of 45% at short-term follow-up (4.4 ± 1.5 months; P < 0.001) and of 53% at long-term follow-up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long-term follow-up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years.

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: The aim of the study was to analyse the lifetime of Soletra implantable pulse generators (IPG) in deep brain stimulation (DBS) of the globus pallidus internus (GPi) for dystonia, depending on stimulation parameters and the total electrical energy delivered (TEED) by the IPG. METHODS: In a prospective series of 20 patients with GPi DBS for dystonia, we recorded IPG longevity and stimulation parameters over time. An evaluation of the TEED was performed using the previously suggested equation [(voltage(2) × pulse width × frequency)/impedance] × 1 s. RESULTS: During median follow-up of 57 months (range 23-79 months), 64 IPGs were replaced because of battery depletion or end of life signal. We found a mean IPG longevity of 25.1 ± 10.1 (range 16-60) months, which was inversely correlated with the TEED (r = -0.72; P < 0.001). IPG longevity was not different between bipolar and monopolar stimulation (24.9 ± 10.8 vs. 25.4 ± 9.0 months, P = 0.76). Incongruously, the mean TEED applied throughout the lifetime cycle was significantly higher in patients with bipolar compared with monopolar stimulation (584 ± 213 vs. 387 ± 121 Joule; P < 0.01). CONCLUSIONS: Battery lifetime in GPi DBS for dystonia is substantially shorter compared with that reported in DBS for Parkinson's disease, caused by a considerably higher voltage and greater pulse width and therefore a higher TEED applied during the battery lifetime cycle. The commonly used equation to calculate TEED, however, seems to be correct only for monopolar, but not bipolar stimulation.

Asunto(s)

RESUMEN

Cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in HIV-infected patients. Diagnosis is based on tests for cryptoccocal antigen in serum and cerebrospinal fluid, and on culture of the organism. We present a case of AIDS-related cryptococcal meningoencephalitis unresponsive to antifungal combination therapy, despite of evidence of fungal susceptibility in vitro. Significant decreases in cryptococcal antigen titers in serum and cerebrospinal fluid did not correlate with progress in disease and fatal outcome.

Asunto(s)

RESUMEN

Several studies have confirmed that subthalamic and pallidal local field potential activity in the beta frequency band (13-30 Hz) is exaggerated in untreated patients with Parkinson's disease (PD) and is suppressed by dopaminergic treatment. This particular spectral pattern differs from that in patients with dystonia in whom pallidal activity is prominent at low frequencies (<12 Hz). Here we demonstrate that tetrabenazine induced monoamine depletion and dopamine blockade is associated with increased activity in the low beta band (13-20 Hz) in the internal pallidum of patients with dystonia. Beta activity was elevated in six patients treated with tetrabenazine compared to six patients in whom this drug was not used. Our findings suggest that beta activity is enhanced in the chronically dopamine-depleted and blocked state irrespective of the underlying pathology, consistent with the idea that excessive synchrony in the beta band is directly related to dopaminergic hypofunction, rather than some degenerative disease-specific attribute of Parkinson's disease.

Asunto(s)