THE USE OF ANTICONVULSANT DRUGS
IN CONTROLLING SEIZURES
Betsy Dayrell-Hart, VMD Dip ACVIM (Neurology)

At the SouthPaws interactive seminars, our referring veterinarians were invited to bring questions and case reports, and to discuss epilepsy and seizure control (among other topics). We talked about neuronal organization in the brain (how neuronal ensembles work under normal and abnormal conditions and how that may lead to seizures), clinical aspects of seizure control, anticonvulsant drugs, or other topics that interest our referring vets. Some of the questions asked during telephone consultations are about how anticonvulsants work.

Seizures are a sign of excessive and uncontrolled discharges in neurons in the cerebral cortex and diencephalon.  Epilepsy research has revealed a number of mechanisms whereby repetitive discharge and synchrony develop in groups of neurons in the cerebral cortex and diencephalon.  These included abnormalities of ion channels resulting in cells having elevated resting potential (closer to threshold) and abnormalities of neurotransmitters (excessive activity of excitatory neurotransmitters such as glutamate, or decreased activity of inhibitory neurotransmitters such as gamma aminobutyric acid - GABA).

The mechanism of action of some anticonvulsant drugs is known. Barbiturates and benzodiazepines enhance the effect of GABA. GABA regulates opening and closing of chloride channels.  When it binds, there is an increased chance of opening of the channel, causing the target neuron to LESS likely discharge repetitively.  Ethosuximide, which is said to be the drug of choice for petit mal seizures, appears to have its effect on one subtype of calcium channels in thalamic neurons, by blocking voltage-dependent channels.  Opening of calcium channels is associated with slow-depolarizing currents in neurons, and makes repetitive discharge of neurons more likely.  The mechanism of action of felbamate is poorly understood.  It seems to increase seizure threshold and prevent electrical spread of seizures, but not by directly affecting GABA receptors or chloride ion channels.  It may reduce sustained repetitive firing of voltage-dependent sodium channels, or indirectly affect N-Methyl-D-aspartate receptors (NMDA, an excitatory amino acid).  It has been shown to bind in several regions of the brain, but which of these is responsible for its anticonvulsant action is unclear.  Gaba pentin is a GABA agonist, but the mechanism by which it affects GABAergic neurotransmitter systems is unknown.

Some anticonvulsants, including older drugs like carbamazepine and newer ones like gaba pentin, are also effective in treating some kinds of neuropathic pain.  These and other drugs may be useful in treating animal patients for conditions other than epilepsy.

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to create a crushed groove for placement of the suture material.  Another easy way to obtain biopsies is to use a 6 or 8 mm skin biopsy punch to obtain a punch section of liver parenchyma (it is better to biopsy a bit closer to the apex where smaller vessels are found).  The liver defect is then filled with a piece of gel foam to quickly stop any venule or capillary bleeding.  The spleen can be similarly biopsied (although cavitated lesions tend to bleed excessively making this technique less practical).

Pancreas
My main comment about the pancreas is to not be too afraid of it.  The pancreas can be safely biopsied by dissecting between lobules, preferably near an apex or a free margin.  Appropriate tissue handling and hemostasis is important, but it is not common to cause a pancreatitis from a simple biopsy.

Kidneys
Kidneys can be biopsied by using either a tru-cut biopsy instrument or by taking a wedge section.  Make sure cortex is included in either technique.  Bleeding can be dramatic, so it is helpful to temporarily occlude the renal vasculature by using either a non-crushing vascular clamp or an assistant's adjacent fingers brought under the kidney and around the vessels.  After a wedge excision, the cut edges of the kidney are digitally held together for five minutes or so until a clot forms.  Mattress sutures are then placed in the capsule to maintain apposition and create a seal against continued bleeding.

Urinary Bladder
I will almost always make my cystotomy incisions on the ventral aspect of the bladder.  This allows easy access to the lumen of the bladder, allows evaluation of the ureters, and is not associated, in my experience anyway, with adhesions to the body wall closure site.  I have seen many dorsal cystotomy incisions adhere to the colon, making subsequent bladder surgeries more difficult.  I will almost always close my cystotomy incisions in one layer, using PDS sutures that include the serosa and muscle layers but exclude the mucosa.  Two layer closures are generally not necessary.

Almost all urethral calculi in male dogs and cats can be retrieved through the cystotomy (so that a separate urethrotomy is not necessary).  To move stones from the urethra into the bladder for retrieval, the tip of the penis is catheterized, pressure is applied over the penis tip to form a seal so that saline can only move retrograde, and then vigorous flushing is applied.  The larger the syringe, the greater the pressure that can be generated.  If needed, I will also stick a finger into the bladder neck to seal this end of the urethra.  As saline is flushed through the catheter and pressure is generated in the urethra, the bladder neck finger is removed, resulting in a big "whoosh" of saline.  This technique usually will dislodge even the most stubborn calculi.

The most accurate way to obtain a urine culture is to submit a small section of the bladder mucosa in a standard culturette (this can be easily done during a cystotomy by excising a small section of mucosa at the cystotomy incision site).