Gait analysis in tumor patients after distal femoral resection and implantation of a megaprosthesis.

We analysed nine patients who had had a megaprosthesis implanted into the distal femur and knee joint for treatment of sarcomas. Data obtained from the leg operated on were compared with those from the contralateral side and healthy volunteers. Gait data, kinematics, ground reaction forces and the EMG from five muscles around the knee joint were analysed by means of a video-based analysis system recording data from reflection markers ; a Kistler-plate recorded the GRF and a ten channel surface EMG the muscle activity. Muscle around the knee showed a cocontraction between the extensor and flexor muscles in the thigh and the calf in the operated leg as well as contralaterally. Gait characteristics exhibited a reduced speed, -cadence, and a shorter step. This correlated with a reduced flexion in the hip and knee joint. The GRF exhibited significant changes in the data representing the reduced gait dynamic.

Characterization of neuronal migration disorders in neocortical structures: extracellular in vitro recordings.

The majority of patients showing neuronal migration disorders in cortical structures suffer from pharmaco-resistant epilepsy. In order to study the molecular and cellular mechanisms underlying this pronounced hyperexcitability, we used an animal model of focal cortical dysplasia demonstrating structural malformations which resemble the human pathology of microgyria. Neocortical slices prepared from adult rats, which at the day of birth received a cortical freeze lesion, were analysed in vitro with an array of eight extracellular recording electrodes to investigate the pattern and pharmacology of propagating epileptiform activity in microgyric cortex. In cortical slices exhibiting neuronal migration disorders, orthodromic synaptic stimulation elicited late recurrent activity and early epileptiform responses that spread with 0.06 m/s over > or = 3.5 mm across the cortex. Application of a N-methyl-D-aspartate (NMDA) antagonist blocked the late recurrent activity, but not the propagation of the early epileptiform responses. The latter were blocked by an (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, indicating that the spread of this activity was predominantly mediated by activation of AMPA receptors. A very similar response pattern could be observed in neocortical slices obtained from untreated age-matched control rats, when the slice was partially disinhibited by bath-application of 5 microM bicuculline methiodide. Stimulus-evoked epileptiform signals recorded in disinhibited slices propagated with 0.08 m/s across the cortex and showed the same sensitivity to ionotropic glutamate antagonists as in dysplastic cortex. Our results indicate that widespread structural and/or functional modifications of the AMPA receptor and possibly also of the gamma-amino-butyric acid type A receptor contribute to the pronounced hyperexcitability in dysplastic cortex.

Characterization of neuronal migration disorders in neocortical structures: I. Expression of epileptiform activity in an animal model.

Hypoxia, ischemia and other forms of brain injury during the pre- and perinatal period may cause neuronal migration disorders which results in irreversible structural modifications. In human neocortex, these malformations have been associated with severe mental retardation, motor dysfunction and the manifestation of therapy-resistant epilepsy. We were interested in analyzing the expression of epileptiform activity in an animal model of neocortical migration disorders. Newborn rats received a focal freeze lesion and were investigated anatomically and in vitro electrophysiologically after survival times of up to five months. Anatomic abnormalities included loss of normal cortical lamination (focal microgyrus) and presence of ectopic cell clusters in layer I and in the white matter (heterotopia). The functional in vitro analyses with eight extracellular recording electrodes revealed a prominent hyperexcitability of the disorganized neocortical network. Electrical stimulation of the afferents elicited epileptiform responses that propagated over > 4 mm in the horizontal direction. In untreated and sham-operated animals, this spread of evoked activity was restricted to 0.5-1 mm. Epileptiform responses were not significantly affected by APV but blocked by NBQX, indicating that AMPA receptors play a prominent role in the generation and propagation of this pathophysiological activity. Our data suggest that the experimentally induced migration disturbances cause long-term structural and/or functional modifications in the neocortical network which may form the basis for the expression of epileptiform activity.