Epilepsy neuronal loss

In human epilepsy, Neuronal loss is well known, especially in the hippocampus. Studies have also found increased concentrations of enolase in human serum and CSF with spontaneous and provoked seizure in subgroups of both children and adults with epilepsy (DeGiorgio et al., 1995). 

Griffiths T., Evans M. C., and Meldrum B. S. (1983). Temporal lobe epilepsy, excitotoxins and the mechanism of selective neuronal loss. In Fuxe K., Roberts P., and Schwarcz R. (eds.), Excitotoxins. Macmillan Publ. Co. Inc., New York, pp. 331-342. 

Meldrum B. S. (1993). Excitotoxicity and selective neuronal loss in epilepsy. Brain Pathol. 3 405 412. 

Du, F., Eid, T., Lothman, E.W., Kohler, C., Schwarcz, R. (1995). Preferential neuronal loss in layer III of the medial enthorinal cortex in rat models of temporal lobe epilepsy. J. Neurosci. 15 6301-13. 

Sutula, TP, Pitkanen, A (2001) More evidence for seiziure-induced neuron loss is hippocampal sclerosis both cause and effect of epilepsy Neurology, 57 169-170. 

It is widely accepted today that prolonged seizures can selectively kill vulnerable neurons. This selective neuronal loss (diffuse cortical atrophy, unilateral hippocampal sclerosis, cerebellar atrophy) was described in the 1800s in institutionalized patients with refractory epilepsy and was assumed to be secondary to hypoxia/ischemia. In the 1970s, after experiments in primates, Meldmm and colleagues proposed that selective hippocampal and neuronal loss resulted from ischemic changes due to local seizure activity lasting 82-120 min (Meldmm, 2002). 

With increasing resolution due to higher Tesla images, volumetric studies show hippocampal and cerebellar volume loss of 3% and neocortical volume loss of 1.6% with an interscan interval of 3.5 years (Lemieux et al., 2000 Liu et al., 2001). Hippocampal atrophy, identified with hippocampal volume measurements, correlates well with hippocampal neuron loss, especially in the CAl sub-region. Decreased ipsilateral thalamic volume has also been documented in temporal lobe epilepsy (Dreifuss et al., 2001 Natsume et al., 2003). 

Primary generalized seizures are also heterogeneous with respect to their clinical features. Such seizures can impose as absence epilepsy, which is characterized by a brief interruption of consciousness due to highly synchronized neuronal activity involving thalamocortical networks without increases in neuronal firing rate. On the other hand, tonic-clonic convulsions with loss of consciousness are often also primarily generalized. 

In some patients, epilepsy worsens over time, with the seizures becoming more frequent as patients grow older. This does not occur in most patients with epilepsy. In those so affected, it is possible that the seizures themselves may cause some damage to the cortex loss of neurons, especially inhibitory neurons, has been demonstrated in tissue from seizure foci. Other changes occur in brain areas affected by seizures reorganization of connections between groups of neurons may strengthen excitatory connections and weaken... 

Schuler, V., Liischer, C., Blanchet, C., et al. (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABAb responses in mice lacking GABAb1. Neuron 31,47-58. 

The neuronal degradation caused by the kainoids closely resembles that seen in patients suffering from neurodegenerative disorders such as Huntington s chorea, Alzheimer s disease, and epilepsy. The neuronal death observed closely mimics the cell loss seen in cases of senile dementia (see Ref. 1 for comprehensive referencing of this research... 

Drags that act on the CNS include those used for the treatment of psychosis, affective (mood) disorders, such as depression and mania, anxieties and related disorders, seizure disorders (epilepsies), Parkinson s disease, Alzheimer s disease, pain (opioid analgesics) and brain tumors. Furthermore, the AIDS virus has a special affinity for the brain, where it attacks neurons and their structural supports (glial cells) causing memory loss, palsy, dementia and, finally, paralysis. 

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