Stephanie Töpfner

Bio: Stephanie Töpfner is an academic researcher from University of Tübingen. The author has contributed to research in topics: Phantom pain & Amputation. The author has an hindex of 6, co-authored 8 publications receiving 857 citations.

Effects of Regional Anesthesia on Phantom Limb Pain Are Mirrored in Changes in Cortical Reorganization

Abstract: The causes underlying phantom limb pain are still unknown. Recent studies on the consequences of nervous system damage in animals and humans reported substantial reorganization of primary somatosensory cortex subsequent to amputation, and one study showed that cortical reorganization is positively correlated with phantom limb pain. This paper examined the hypothesis of a functional relationship between cortical reorganization and phantom limb pain. Neuroelectric source imaging was used to determine changes in cortical reorganization in somatosensory cortex after anesthesia of an amputation stump produced by brachial plexus blockade in six phantom limb pain patients and four pain-free amputees. Three of six phantom limb subjects experienced a virtual elimination of current phantom pain attributable to anesthesia (mean change: 3.8 on an 11-point scale; Z = −1.83; p < 0.05) that was mirrored by a very rapid elimination of cortical reorganization in somatosensory cortex (change = 19.8 mm; t (2) = 5.60; p < 0.05). Cortical reorganization remained unchanged (mean change = 1.6 mm) in three phantom limb pain amputees whose pain was not reduced by brachial plexus blockade and in the phantom pain-free amputation controls. These findings suggest that cortical reorganization and phantom limb pain might have a causal relationship. Methods designed to alter cortical reorganization should be examined for their efficacy in the treatment of phantom limb pain.

The cortical somatotopic map and phantom phenomena in subjects with congenital limb atrophy and traumatic amputees with phantom limb pain

Abstract: The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-D-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain

Abstract: In the present study we investigated the effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.

Continuous brachial plexus analgesia and NMDA-receptor blockade in early phantom limb pain: a report of two cases.

Abstract: Objective. To provide a mechanism-based acute pain management strategy for early phantom limb pain following traumatic amputations and to collect first evidence of its acute and potentially preventative effects on the formation and maintenance of phantom limb pain. The combination of continuous brachial plexus analgesia and prolonged block of N-methyl-D-aspartate (NMDA) receptors over 4 weeks aimed to attenuate peripheral and central sensitization, currently thought to be substantially involved in establishing and maintaining phantom limb pain. Case Report. Two patients, after traumatic upper limb amputations and early phantom limb pain, were treated on the second and fifth day following amputation by continuous brachial plexus analgesia with ropivacaine 0.375% (30 ml for the initial block, continuous infusion rate = 5 ml/h) for 5 (Patient 1) and 9 days (Patient 2). Both patients received oral memantine (a noncompetitive NMDA-receptor antagonist) in increasing doses from 10 to 30 mg/d over a 4-week period. Ropivacaine only produced minor motor block, with almost unimpaired motor function. Memantine was well tolerated and no relevant side effects were observed. In both patients the treatment prevented the establishment of phantom limb pain, which did not reappear during follow-up of 1 year. Conclusions. The combination of long-term regional analgesia with prolonged block of NMDA receptors might be effective for treatment and prevention of phantom limb pain following traumatic amputations. The absence of clinically relevant side effects, together with maintained motor function suggests this treatment to be a promising preventive strategy for phantom limb pain following traumatic amputations.

Words in the brain's language.

Abstract: If the cortex is an associative memory, strongly connected cell assemblies will form when neurons in different cortical areas are frequently active at the same time. The cortical distributions of these assemblies must be a consequence of where in the cortex correlated neuronal activity occurred during learning. An assembly can be considered a functional unit exhibiting activity states such as full activation ("ignition") after appropriate sensory stimulation (possibly related to perception) and continuous reverberation of excitation within the assembly (a putative memory process). This has implications for cortical topographies and activity dynamics of cell assemblies forming during language acquisition, in particular for those representing words. Cortical topographies of assemblies should be related to aspects of the meaning of the words they represent, and physiological signs of cell assembly ignition should be followed by possible indicators of reverberation. The following postulates are discussed in detail: (1) assemblies representing phonological word forms are strongly lateralized and distributed over perisylvian cortices; (2) assemblies representing highly abstract words such as grammatical function words are also strongly lateralized and restricted to these perisylvian regions; (3) assemblies representing concrete content words include additional neurons in both hemispheres; (4) assemblies representing words referring to visual stimuli include neurons in visual cortices; and (5) assemblies representing words referring to actions include neurons in motor cortices. Two main sources of evidence are used to evaluate these proposals: (a) imaging studies focusing on localizing word processing in the brain, based on stimulus-triggered event-related potentials (ERPs), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), and (b) studies of the temporal dynamics of fast activity changes in the brain, as revealed by high-frequency responses recorded in the electroencephalogram (EEG) and magnetoencephalogram (MEG). These data provide evidence for processing differences between words and matched meaningless pseudowords, and between word classes, such as concrete content and abstract function words, and words evoking visual or motor associations. There is evidence for early word class-specific spreading of neuronal activity and for equally specific high-frequency responses occurring later. These results support a neurobiological model of language in the Hebbian tradition. Competing large-scale neuronal theories of language are discussed in light of the data summarized. Neurobiological perspectives on the problem of serial order of words in syntactic strings are considered in closing.

Constraint-Induced Movement Therapy: a new family of techniques with broad application to physical rehabilitation--a clinical review.

Abstract: A new family of rehabilitation techniques, termed Constraint-Induced Movement Therapy or CI Therapy, has been developed that controlled experiments have shown is effective in producing large improvements in limb use in the real-world environment after cerebrovascular accident (CVA). The signature therapy involves constraining movements of the less-affected arm with a sling for 90% of waking hours for 2 weeks, while intensively training use of the more-affected arm. The common therapeutic factor in all CI Therapy techniques would appear to be inducing concentrated, repetitive practice of use of the more-affected limb. A number of neuroimaging and transcranial magnetic stimulation studies have shown that the massed practice of CI Therapy produces a massive use-dependent cortical reorganization that increases the area of cortex involved in the innervation of movement of the more-affected limb. The CI Therapy approach has been used successfully to date for the upper limb of patients with chronic and subacute CVA and patients with chronic traumatic brain injury and for the lower limb of patients with CVA, incomplete spinal cord injury, and fractured hip. The approach has recently been extended to focal hand dystonia of musicians and possibly phantom limb pain.

Electromyogram pattern recognition for control of powered upper-limb prostheses: state of the art and challenges for clinical use.

Abstract: Using electromyogram (EMG) signals to control upper-limb prostheses is an important clinical option, offering a person with amputation autonomy of control by contracting residual muscles. The dexterity with which one may control a prosthesis has progressed very little, especially when control- ling multiple degrees of freedom. Using pattern recognition to discriminate multiple degrees of freedom has shown great promise in the research literature, but it has yet to transition to a clinically viable option. This article describes the pertinent issues and best practices in EMG pattern recognition, identifies the major challenges in deploying robust control, and advocates research directions that may have an effect in the near future.

Phantom limb pain: a case of maladaptive CNS plasticity?

Abstract: Phantom pain refers to pain in a body part that has been amputated or deafferented. It has often been viewed as a type of mental disorder or has been assumed to stem from pathological alterations in the region of the amputation stump. In the past decade, evidence has accumulated that phantom pain might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human studies and derive suggestions for innovative interventions aimed at alleviating phantom pain.