THE TIN MAN GUIDE TO STIFF-PERSON SYNDROME
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Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABA-α receptors, the GAT-1 GABA transporter, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatory glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA. This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act proconvulsively. In addition to barbituates and benzodiazepines which have already been covered, there are other classes of antiseizure and anticonvulsant medications that may be prescribed for patients with seizure activity and myoclonus.


1. Levetiracetam, Keppra


Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures, or as an adjunctive therapy for partial, myoclonic and tonic-clonic seizures. Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, autism, bipolar disorder, and anxiety disorder, as well as Alzheimer's disease. However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood.


It is also sometimes used to treat neuropathic pain. It has not been found to be useful for essential tremors. The drug binds to a synaptic vesicle glycoprotein, SV2A,and inhibits presynaptic calcium channels. This is believed to impede impulse conduction  across synapses. A study published in 2005 suggests that the addition of pyridoxine (vitamin B6) may curtail some of the psychiatric symptoms. A rare side effect of Levetiracitam is a pins and needles sensation in the patient's legs, similar to neuropathy. Drugs.com.


1. Rüegg SJ, Steck AJ, Fuhr P. Levetiracetam improves paroxysmal symptoms in a patient with stiff-person syndrome. Neurology. 2004 Jan 27;62(2):338. Link to article


2. Sechi G, Barrocu M, Piluzza MG, et al. Levetiracetam in stiff-person syndrome. J Neurol 2008;255:1721-5

Link to article


3. Shimberg WR, Patel NB, Sullivan KL, Hauser RA, Zesiewicz TA. Levetiracetam for stiff-person syndrome: report of 2 patients. Clin Neuropharmacol. 2008 Sep-Oct;31(5):301-2. doi: 10.1097/WNF.0b013e31815f8df0.

Link to article


2. Stiripentol, Diacomet


It increases GABA transmission through a barbiturate-like effect, since it increases the duration of opening of GABA-α receptors channels in hippocampal slices. It has also been shown that STP may increase the GABA levels in brain tissues and by interfering with its uptake and its metabolism. It also improves the effectiveness of many other anti-convulsants, possibly due to it inhibiting certain enzymes. This slows the drug's metabolism, increasing blood plasma levels. Drugs.com.


3. Oxcarbazepine, Trileptal


In treatment of epilepsy, oxcarbazepine has recently been found to be associated with a greater enhancement in mood and reduction in anxiety symptoms than other drugs employed to treat epilepsy. It also appears to be effective in approximately half of patients with bipolar disorder and is well tolerated. It is a structural derivative of carbamazepine, with a ketone in place of the carbon–carbon double bond on the dibenzazepine ring at the 10 position (10-keto). This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine – sodium channel inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions. Drugs.com.


4. Depacon, Valproate


Sodium valproate can be used to control acute episodes of mania and acute stress reaction. Side effects can include tiredness, tremors, nausea, vomiting and sedation. The intravenous formulations are used when oral administration is not possible. Drugs.com


1. Murinson B. Stiff-person syndrome. Johns Hopkins.School of Medicine.  Link to article.


2. Todman D. Stiff-Person Syndrome (Moersch-Woltman Syndrome). The Internet Journal of Neurology. 2006 Volume 7 Number 1.  Link to article


5. Eslicarbazepine acetate, Aptiom, Zebinix, Exalief (ESL)

ESL is an anticonvulsant used as an adjunctive therapy for epilepsy, trigeminal neuralgia, and bipolar disorder. Similarly to oxcarbazepine, their mechanisms of action are identical. However, there may be pharmacokinetic differences between the two drugs; for instance, ESL may not produce as high of peak levels of (S)-(+)-licarbazepine immediately after dosing as does oxcarbazepine, which could, in theory, improve tolerability. Drugs.com.


6. Ethotoin, Peganone


Ethotoin is an anticonvulsant drug used in the treatment of epilepsy. It is a hydantoin, similar to phenytoin. Ethotoin lacks phenytoin's side effects of gingival hyperplasia and hirsutism, however it is less effective. This, combined with the need for frequent dosing has limited its usefulness. Ethotoin is no longer widely used. Drugs.com.


7. Phenytoin, Dilantin, Phenytek, Phenytoin Sodium, Prompt, Di-Phen


Pheyntoin is a hydantoin-derivative anticonvulsant drug used primarily in the management of complex partial seizures and generalized tonic-clonic seizures. Phenytoin is also used to prevent seizures following neurosurgery. Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage-gated sodium channels. Additionally, phenytoin is a class 1b antiarrhythmic that can be used to treat cardiac arrhythmias when conventional options have failed or after cardiac glycoside intoxication. Side effects include gingival hyperplasia and hirsutism. Drugs.com.


8. Fosphenytoin, Prodilantin, Cerebyx


Fosphenytoin is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin and is potentially more safely than intravenous phenytoin. It is most commonly used in the acute treatment of convulsive status epilepticus. Drugs.com.


9. Zaleplon, Sonata, Starnoc, Andante


It is almost entirely used for the management/treatment of insomnia. It works by depressing the central nervous system causing drowsiness. Long term use can lead to adverse effects such as cognitive impairment, anterograde amnesia, daytime sedation, musculoskeletal impairment, and an increased risk of harm to oneself (e.g. falling) and to others (e.g. automotive accidents). Drugs.com.


10. Zolpidem


It is a specific agonist at the benzodiazepine GABA-α α1 sub-receptor site. It also modulates the GABA-α sub-sites, α2 and α3, to a lesser degree. It has no statistical significance as an anticonvulsant.  It is a short-acting nonbenzodiazepine hypnotic that potentiates GABA by binding to GABA-α receptors at the same location as benzodiazepines. It works quickly, usually within 15 minutes, and has a short half-life of two to three hours.  Drugs.com.


11. Zopiclone, Zimovane, Imovane, Lunesta


It is a specific agonist at the benzodiazepine GABA-α α1 sub-receptor site. It also modulates the GABA-α sub-sites, α2 and α3, to a lesser degree. It has no statistical significance as an anticonvulsant. Zopiclone is sedating and is marketed as a sleeping pill. It works by causing a depression or tranquilization of the central nervous system. After prolonged use, the body can become accustomed to the effects. When the dose is then reduced or the drug is stopped, withdrawal symptoms may result. These can include a range of symptoms similar to those of benzodiazepine withdrawal. In the US its active stereoisomer, eszopiclone, is sold under the name Lunesta. Drugs.com


ANTISEIZURE MEDICATION

Treatment options  GABAergic drugs   GABA A Agonists   GABA Modulators   GABA B Agonists   GABA P Agonists


GABA Transaminase   GABA RUI   GABA Analogues   GABA Supplement   Muscle Relaxers   Corticosteroids


Antiseizure   Opiate Analgesics   Experimental   IVIG   Plasmapheresis   Immunotherapy   Stem Cell Therapy  PT