Increased incidence of cage migration and nonunion in instrumented transforaminal lumbar interbody fusion with bioabsorbable cages.

OBJECT: Recent advances in the field of spinal implants have led to the development of the bioabsorbable interbody cage. Although much has been written about their advantageous characteristics, little has been reported regarding complications associated with these cages. The authors conducted this prospective cohort study to compare fusion and complication rates in patients undergoing transforaminal lumbar interbody fusion (TLIF) with carbon fiber cages versus biodegradable cages made from 70/30 poly(l-lactide-co-d,l-lactide) (PLDLA). METHODS: Between January 2005 and May 2006, 81 patients with various degenerative and/or structural pathologies affecting the lumbar spine underwent single- or multilevel TLIF with posterior segmental pedicle screw fixation using implants made of carbon fiber (37 patients) or 70/30 PLDLA (44 patients). Clinical and radiological follow-up was performed at 6 weeks, 3 months, 6 months, and 1 year, and is ongoing. The incidence of nonunion, screw breakage, and cage migration were compared between the 2 groups. RESULTS: There was no significant difference in demographic data between the 2 groups, the mean number of lumbar levels operated, or distribution of the levels operated. There was a significantly increased incidence of nonunion (8 patients, 18.2%) and cage migrations (8 patients, 18.2%) in patients receiving the PLDLA implants compared with carbon fiber implants (no patients) (p = 0.006 and 0.007, respectively). There was no significant difference in demographic data between patients with cage migration and the rest of the patient population. Five of the 8 cases of migration occurred at the L5-S1 level while the remaining 3 occurred at the L4-5 level. The mean time to implant failure was 9.3 months. CONCLUSIONS: This study showed an increased incidence of nonunion (18.2%) and postsurgical cage migration (18.2%) in patients undergoing TLIF with biodegradable cages versus carbon fiber implants (0%) (p = 0.006 and 0.007, respectively).

Energetics of neuronal signaling and fMRI activity.

Energetics of resting and evoked fMRI signals were related to localized ensemble firing rates (nu) measured by electrophysiology in rats. Two different unstimulated, or baseline, states were established by anesthesia. Halothane and alpha-chloralose established baseline states of high and low energy, respectively, in which forepaw stimulation excited the contralateral primary somatosensory cortex (S1). With alpha-chloralose, forepaw stimulation induced strong and reproducible fMRI activations in the contralateral S1, where the ensemble firing was dominated by slow signaling neurons (SSN; nu range of 1-13 Hz). Under halothane, weaker and less reproducible fMRI activations were observed in the contralateral S1 and elsewhere in the cortex, but ensemble activity in S1 was dominated by rapid signaling neurons (RSN; nu range of 13-40 Hz). For both baseline states, the RSN activity (i.e., higher frequencies, including the gamma band) did not vary upon stimulation, whereas the SSN activity (i.e., alpha band and lower frequencies) did change. In the high energy baseline state, a large majority of total oxidative energy [cerebral metabolic rate of oxygen consumption (CMR(O2))] was devoted to RSN activity, whereas in the low energy baseline state, it was roughly divided between SSN and RSN activities. We hypothesize that in the high energy baseline state, the evoked changes in fMRI activation in areas beyond S1 are supported by rich intracortical interactions represented by RSN. We discuss implications for interpreting fMRI data where stimulus-specific DeltaCMR(O2) is generally small compared with baseline CMR(O2).

Lamotrigine suppresses neurophysiological responses to somatosensory stimulation in the rodent.

Neurotransmitter release and voltage-gated ion channel activity in excitatory neurons are critical for understanding and interpreting neuroimaging signals. Couplings between changes in neural activity and energetic/vascular responses are assumed for interpretation of neuroimaging signals. To investigate involvement of neural events to neuroenergetic/neurovascular responses, we conducted multi-modal magnetic resonance imaging (MRI) measurements (at 7.0 T) and electrophysiological recordings (with high impedance microelectrodes) for local field potential (LFP) and spiking frequency (nu) in alpha-chloralose-anesthetized rats. The rats underwent forepaw stimulation before and after treatment of lamotrigine, a neuronal voltage-gated ion channel blocker and glutamate release inhibitor. Multi-modal MRI measurements of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signal were combined to estimate changes in cerebral metabolic rate of oxygen consumption (CMRo2). Lamotrigine did not appreciably affect values of nu, CBF, and CMRo2 in the resting state. After lamotrigine treatment, evoked changes in LFP and nu were attenuated, which were consistent with commensurate declines in deltaCBF and deltaCMRo2. While number of evoked BOLD-activated voxels was considerably reduced with lamotrigine, intensities of voxels in middle cortical layers were affected to a lesser degree by lamotrigine. The results suggest that lamotrigine suppresses evoked neurophysiological (i.e., neural/energetic/vascular) responses, both in terms of volume of tissue activated and degree of activation in the foci. Since lamotrigine affects evoked responses but not the basal signals, it can be suggested that glutamate release and activity of voltage-gated ion channels are essential for initiating evoked energetic/vascular responses, and thereby important for interpretation of incremental changes in neuroimaging signal.

Selective frontal, parietal, and temporal networks in generalized seizures.

Are "generalized" seizures truly generalized? Generalized tonic-clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic-clonic seizures. Study of human tonic-clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic-clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. (99m)Tc-hexamethylpropylene amine oxime injections during seizures provide a "snapshot" of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic-clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI.

Functional MRI (fMRI) is widely assumed to measure neuronal activity, but no satisfactory mechanism for this linkage has been identified. Here we derived the changes in the energetic component from the blood oxygenation level-dependent (BOLD) fMRI signal and related it to changes in the neuronal spiking frequency in the activated voxels. Extracellular recordings were used to measure changes in cerebral spiking frequency (Deltanu/nu) of a neuronal ensemble during forepaw stimulation in the alpha-chloralose anesthetized rat. Under the same conditions localized changes in brain energy metabolism (DeltaCMR(O2)/CMR(O2)) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (DeltaCBF/CBF), cerebral blood volume (DeltaCBV/CBV), and transverse relaxation rates of tissue water (T(2)(*) and T(2)) by MRI methods at 7T. On stimulation from two different depths of anesthesia DeltaCMR(O2)/CMR(O2) approximately Deltanu/nu. Previous (13)C magnetic resonance spectroscopy studies, under similar conditions, had shown that DeltaCMR(O2)/CMR(O2) was proportional to changes in glutamatergic neurotransmitter flux (DeltaV(cyc)/V(cyc)). These combined results show that DeltaCMR(O2)/CMR(O2) approximately DeltaV(cyc)/V(cyc) approximately Deltanu/nu, thereby relating the energetic basis of brain activity to neuronal spiking frequency and neurotransmitter flux. Because DeltaCMR(O2)/CMR(O2) had the same high spatial and temporal resolutions of the fMRI signal, these results show how BOLD imaging, when converted to DeltaCMR(O2)/CMR(O2), responds to localized changes in neuronal spike frequency.