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Автор Тема: Кучешка епилепсия  (Прочетена 14419 пъти)
Иван Панайотов - vano
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« -: 25.06.2011 22:42:22 »

Canine Epilepsy

Author
Alicia Wiersma-Aylward (wiersma.jelle@pi.net)

Introduction
It happened without warning. One moment my young male Belgian Tervueren was snuggling against me as I sat on the couch; the next moment he lost control of his hindquarters and fell onto his side, unconscious. His lips writhed back over his teeth; his legs stretched out, then became rigid; and his head twisted up and back as if an unseen hand was trying to raise his chin to an impossible height. It seemed like an eternity, but actually only two minutes passed before his body relaxed and consciousness slowly ebbed back. For an hour afterward he seemed exhausted and disoriented. I was shaken too, never having witnessed such a seizure before. Yet later that day the dog was romping about as if nothing out of the ordinary had occurred.

My dog is lucky. His seizures have been few and far between. We now believe they are caused by hypothyroidism. Other dogs are not so lucky. Seizures can be severe and frequent. They may occur in "clusters" (several in one day), or progress to the life-threatening state of status epilepticus. In extreme cases where seizures cannot be controlled, a veterinarian may advise euthanasia.

Epilepsy is found in all breeds and mixed breeds of dogs. Belgian Tervueren are listed among the breeds for which a genetic factor is either proved or highly suspected. Other breeds so listed include the Beagle, Dachshund, German Shepherd Dog, (Alsatian), and Keeshond. A high incidence of seizure disorders is also found in Boxers, Cocker Spaniels, Collies, Golden Retrievers, Irish Setters, Labrador Retrievers, Miniature Schnauzers, Poodles, Saint Bernards, Siberian Huskies, and Wire-Haired Terriers. (Oliver, Seizures). The prevalence of epilepsy in the general dog population has been estimated at .5 to 5.7%. (Koestner, Cunningham).

A progress report on the epilepsy survey conducted by the American Belgian Tervuren Club in cooperation with John Oliver, Jr., DVM in 1983 found that 57 (21%) of the 268 Tervueren studied had suffered more than one seizure. The authors of that report concluded, "At this time, we believe there is sufficient evidence for the probable genetic basis of seizures in Tervuren to warrant concern on the part of breeders". (Mahaffey). Unfortunately, this survey was discontinued.

The term "epilepsy" can be confusing because some authors use it to describe recurrent seizures of any etiology (cause), while others use it to specify recurrent seizures unrelated to brain disorders or underlying disease processes. (Shell, Understanding). The definitions below are helpful in distinguishing types of epilepsy.

Types of Epilepsy
Primary epilepsy: also known as idiopathic, genetic, inherited, or true epilepsy. There are no positive diagnostic findings that will substantiate the diagnosis. It is a case of ruling out every other possibility. The first seizure in a dog with primary epilepsy usually occurs between the ages of 6 months and 5 years. (Oliver, Seizures). However, a diagnosis of primary epilepsy is not proof of a genetic defect; only careful breeding studies could prove that. The breed, the age, and the history may suggest a genetic basis for primary epilepsy if there is a familial history of seizures.

Secondary epilepsy refers to seizures for which a cause can be determined, and there are many. In dogs less than one year of age, the most commonly-found causes of seizures can be broken down into the following classes: degenerative (storage diseases); developmental (hydrocephalus); toxic (lead, arsenic, organophosphates, chlorinated hydrocarbons, strychnine, tetanus); infectious (distemper, encephalitis, and others); metabolic (such as transient hypoglycemia, enzyme deficiency, liver or kidney failure); nutritional (thiamine, parasitism); and traumatic (acute injury). In dogs 1-3 years of age, a genetic factor is most highly suspected. In dogs 4 years of age and older, seizures are commonly found in the metabolic (hypoglycemia, cardiovascular arrhythmia, hypocalcemia, cirrhosis) and neoplastic (brain tumor) classes. (Oliver, Seizure). Dr. Jean Dodds has mentioned that seizures are also associated with hypothyroidism, which is a familial (inherited) autoimmune disease of purebred dogs.

Types of Seizures
The types of seizures most commonly reported are listed below. If you believe your dog is having a seizure, it is important to note all the details so that you may accurately describe it to your veterinarian. Types of seizures include:

Generalized Seizure: Tonic-clonic (may be Grand Mal or Mild): In the grand mal seizure, the tonic phase occurs as the animal falls, loses consciousness, and extends its limbs rigidly. Respiration also stops (apnea). This phase usually lasts 10-30 seconds before the clonic phase begins. Clonic movements include paddling of the limbs and/or chewing. Other signs that appear during the tonic or clonic phase are dilation of the pupils, salivation, urination, and defecation. The mild seizure involves little or no paddling or extension of limbs, and usually no loss of consciousness. Generalized seizures are usually associated with primary epilepsy.

Petit Mal Seizure (aka Absence Seizure): Depending on the authority quoted, petit mals are described as either very rare or usually unrecognized in animals. Signs are brief (seconds) duration of unconsciousness, loss of muscle tone, blank stare, and possibly upward rotation of eyes. According to one authority (Kay), the term petit mal is misused by veterinarians and should only be accorded to cases manifesting very specific clinical signs and EEG abnormalities.

Partial Seizures: Movements are restricted to one area of the body, such as muscle jerking, movement of one limb, turning the head or bending the trunk to one side, or facial twitches. A partial seizure can progress to (and be mistaken for) a generalized tonic-clonic seizure, but the difference can be established by noting whether or not a seizure starts with one specific area of the body. Partial seizures are usually associated with secondary epilepsy.

Complex Partial Seizures (aka Psychomotor or Behavioral) Seizures: are associated with bizarre or complex behaviors that are repeated during each seizure. People with complex partial seizures experience distortions of thought, perception or emotion (usually fear), sometimes with unusual visual, olfactory, auditory and gustatory sensations. If dogs experience the same things, it may explain the lip-smacking, chewing, fly biting, aggression, vocalization, hysterical running, cowering or hiding in otherwise normal animals. Vomiting, diarrhea, abdominal distress, salivation, blindness, unusual thirst or appetite, and flank biting are other signs. There is an obvious lack of awareness though usually not lack of consciousness. Abnormal behaviors may last minutes or hours and can be followed by a generalized seizure. Complex partial seizures are usually associated with secondary epilepsy.

Cluster Seizures: Multiple seizures within a short period of time with only brief periods of consciousness in between. May be confused with status epilepticus.

Status Epilepticus: Status can occur as one continuous seizure lasting 30 minutes or more, or a series of multiple seizures in a short time with no periods of normal consciousness. It can be difficult to tell status epilepticus from frequent cluster seizures; but both are considered life-threatening emergencies. Most status patients usually suffer from generalized tonic-clonic seizures. Though status epilepticus can occur with either primary or secondary epilepsy, it may also suddenly arise in dogs with no previous history of seizures (traumatic brain injury, toxins, or disease). (Dyer & Shell, Managing).

What is a "seizure threshold"?
Dr. Alexander de Lahunta of Cornell University and others suggest that each animal inherits a "genetically determined predisposition to seizures", and that seizures occur when this threshold is exceeded. (Cunningham, Inherited). In other words, a physical condition (see examples under section on secondary epilepsy above) which may cause seizures in a low-threshold animal may not cause seizures in a "normal" animal.

The seizure threshold is apparently exceptionally low in animals that suffer from idiopathic (primary) epilepsy. (de Lahunta). An animal's threshold can also be altered by other means. Certain types of tranquilizers (e.g. acepromazine) may induce seizures in animal with a low threshold. The medical condition of alkalosis is reported to decrease the threshold. (Shell, Differential)

Karen R. Dyer, DVM, PH.D, and Linda G. Shell, DVM, Dilp. ACVIM, note that there is "convincing experimental evidence" that repetitive seizures can "irreversibly lower the seizure threshold" in a process called kindling. William Fenner, DVM and Julie Haas, DVM, describe kindling as a mechanism in which epileptic neurons in the brain "recruit" normal neurons into the original seizure focus, enlarging the area of the brain that can produce seizures. Linda Shell, DVM describes kindling as the "increased excitability of neurons", and notes that normal neurons, sufficiently stimulated, become increasingly able to cause seizures independent of outside stimulation.

The mirror focus phenomenon also deserves mention. Each hemisphere of the brain is a "mirror image" of the other. A seizure focus on one side of the brain will show itself as abnormal wave forms on EEG recordings. Within a period of weeks, the "normal" side of the brain will start to show similar EEG abnormalities. In time, the mirror focus becomes capable of causing seizure activity on its own. Thus, repetitive, uncontrolled seizures also lower the seizure threshold in any given animal. That is why early intervention is so important in the control of seizures.

Stages of a Seizure
There are 4 basic stages to a seizure: 1) the prodome, 2) the aura or preictus, 3) the ictus or seizure stage, and 4) the postictus.

1) The prodome may precede the actual seizure by hours or days. It is characterized by a change in mood or behavior. Human epileptics experience mood changes, headaches, insomnia or feelings about the impending seizure. It is not known whether animals experience a prodome except for any behavioral changes observed by their owners.

2) The aura signals the start of the seizure. Signs include restlessness, nervousness, whining, trembling, salivation, affection, wandering, hiding, hysterical running, and apprehension.

3) The ictus is the actual seizure, characterized by sudden increase in tone of all muscle groups. The ictus is either tonic or tonic-clonic, generally lasting from 1-3 minutes.

4) The postictus may be the only sign of epilepsy the owner sees, particularly since many seizures occur at night or early in the morning. For minutes to days after the seizure, the dog may be confused, disoriented, restless, or unresponsive, or may wander or suffer from transient blindness. At this stage the animal is conscious but not functional. (Shell, Understanding; Kay; Oliver, Seizures).

What can you do when your dog seizures? Note the time to determine how long the seizure lasts. Keep the dog as quiet as possible. Loud or sharp noises may prolong the seizure or make it worse. Other dogs should be removed from the area, as they may disturb or attack the seizuring dog. Should you attempt to comfort the animal? Opinions on this vary. My own dog is comforted by my presence and looks for me as he returns to consciousness. I make a point of calmly maintaining physical and voice contact with him throughout the seizure and during recovery.

Diagnosing Epilepsy
What do you do if you think your dog has had a seizure? Veterinarians have a number of diagnostic tools at their disposal.

For dogs who have had only one isolated seizure, a complete physical and neurological examination is in order. Owners will be advised to watch for further seizures if no abnormalities are found. Medical treatment will not be instituted until future activity can be noted.

For every patient having more than one seizure, a minimum data base should be developed. The data base contains the patient's profile, history, results of complete physical and neurological examinations, and basic tests. The profile consists of the dog's breed, age, and sex. Pertinent history includes vaccinations, potential exposure to toxins, diet, any illnesses or injuries, behavioral changes, and whether seizures occurred in any animal related to the dog.

Owners are also asked to give a complete description of the seizures: frequency, duration, and severity, as well as any behavioral abnormalities associated with them. An accurate description is important because there are other conditions with symptoms that mimic seizures, such as cardiac and/or pulmonary disease, narcolepsy, cataplexy, myasthenia gravis, and metabolic disturbances.

Among the recommended tests are: CBC, urinalysis, BUN, ALT, ALP, calcium, fasting blood glucose level, serum glucose level, serum lead level, fecal parasite or ova examination, and others if indicated. When the results of the examinations and tests have been analyzed, one of three conclusions will be drawn: a definitive diagnosis, a potential cause of seizures requiring further tests to confirm, or no suggestion of a cause.

When further tests are required a complete date base should be done. This may include computed tomography or magnetic resonance imaging; CSF analysis (cell count, protein levels, pressure), skull radiographs, and an EEG.

Treatment
Medical treatment is generally advised for animals who have one or more seizures per month. Animals who have cluster seizures or go into status epilepticus may be treated even though the rate of incidence is greater than once per month. Successful drug therapy depends upon the owner's dedication to delivering the drug exactly as prescribed, with absolutely NO changes in the dose or type of medication without veterinary consultation. Haphazard drug administration or abrupt changes in medication is worse than no treatment at all, and may cause status epilepticus.

William Thomas, DVM, MS feels it important to remember that the goal of treatment is to decrease the frequency and severity of seizures and avoid unacceptable side effects. It may not be possible to stop the seizures altogether. A number of drugs and some alternative therapies may be used to control epilepsy. Phenobarbitol and primidone are the most widely used anticonvulsant drugs, but others have their place in treatment as well.

Phenobarbitol is one of the most commonly prescribed drugs. Frey reports that while dogs rapidly develop tolerance to the sedative and hypnotic effects of phenobarbitol, at high concentrations tolerance may be lost and persistent depressive side effects may appear. Dogs may eat or drink more than their usual amounts. Liver function can be impaired. When use of the drug is terminated, signs of physical dependence (tremors, incoordination, restlessness, seizures) may develop. There is danger of triggering status epilepticus during withdrawal. To avoid this, dosages should be gradually reduced in small steps over a prolonged period.

Primidone's side effects include sedation when treatment is initiated, and eating or drinking more than usual. High concentrations of liver enzymes have been reported with prolonged treatment at high dosages.

Diazepam (Valium) is used for treatment of status epilepticus. Phenytoin (Dilantin), carbamazine, and valproic acid are not currently recommended for use.

Potassium bromide (KBr) is gaining new recognition for use in refractory (difficult to control) canine epilepsy, though used to treat human epileptics as early as 1857. It is the anticonvulsant of choice for dogs with liver disease. Sodium bromide is preferred for dogs with kidney problems. Combining potassium bromide or sodium bromide and phenobarbitol may be useful for patients who do not respond well to phenobarbital or primidone alone.

One recent study (Pearce) reported that 10 dogs who had uncontrolled seizures with phenobarbitol alone had improved control with the addition of potassium bromide to their drug regimen. The severity of the seizures and the tendency to cluster were significantly decreased. An earlier study by Professor Dorothea Schwartz-Porsche (Sisson/LeCouteur) reported that 5 of 9 epileptics uncontrolled by phenobarbitol responded to the addition of potassium bromide to either phenobarbitol or primidone. Podell and Fenner reported that bromide therapy improved seizure control in 83% of dogs previously unimproved by phenobarbitol; 26% of the 83% dogs became totally seizure free.

Bromide is not approved for use in dogs, nor is it commercially available at this time. Veterinarians can obtain it from chemical supply houses as an American Chemical Society reagent, which dissolves in water and is added to the dog's food. Dog owners are asked to sign release forms and are advised to handle the drug with gloves. Thomas notes that some custom pharmacies will now formulate bromide in capsules or suspension so the veterinarian doesn't have to.

Side effects of bromide toxicity (bromism) can include incoordination, depression, muscle pain, and stupor. There are no dermatologic or gastrointestinal signs as seen in humans taking KBr.

Monitoring Drug Treatment
In order for any drug therapy to be effective, the amount of drug found in the body (serum concentration) must be consistently monitored. No two animals may react to the same dose in the same way. Farnbach reports a sixfold variation in the ratio between daily dosage and serum concentration was demonstrated in a large population of epileptic dogs. In 3 dogs given roughly the same dose of phenobarbitol, one dog's condition did not change, the second dog achieved seizure control, and the third dog experienced toxicosis. The amount of drug found in the body correlates much better with seizure control than daily dosage.

If your dog is on medication, work with your veterinarian in observing your dog and testing his/her serum levels to ensure he/she is receiving the appropriate amount of drug to achieve control and avoid side effects.

Why Treatment Fails
There are many reasons why medical treatments can fail. The biggest reason is the owner's lack of proper administration of the prescribed drug. The progression of an underlying disease (such as brain tumor) may resist treatment. Also, gastrointestinal disorders can affect drug absorption, and tranquilizers may stimulate seizures. Drug interactions can occur and adversely affect the level of anticonvulsant drug in the dog's system. And it just might be that a particular drug may not work for that animal. (LeCouteur).

Alternative Therapies
These range from acupuncture to vitamin therapy. Traditional acupuncture therapy for epileptic dogs involves the placement of needles in up to 10 areas of the body. Needles can be left in place from 20 minutes to over a month.

Acupuncture is not usually considered a substitute for drug therapy, but is used in conjunction with them. Of 5 dogs with intractable epilepsy, followed after gold bead implants in acupuncture points, 2 dogs relapsed after five months. Two reports of epileptic dogs given acupuncture in the ear (Shen-men point) are more positive. One dog enjoyed a six-fold increase in time between seizures; the other was seizure-free for 200 days after a previous history of monthly seizures. (Joseph, van Niekerk).

Holistic veterinarian Roger DeHaan, DVM states that some forms of epilepsy respond to supplementation of vitamin B6, magnesium, and manganese. Drs. Wendell Belfield and Martin Zucker stated that "It has long been known that a deficiency of vitamin B6 or any interference with its function can cause seizures in any mammalian species, including man and dog".

Parting Considerations
If your dog is experiencing either mild or severe seizures, there is help for both of you. Work with a veterinary professional with whom you feel a good rapport, and educate yourself on seizures and their treatment. Follow the vet's instructions, never change medication or dosages without a consultation, be observant, monitor serum levels as recommended, have patience and be willing to try another form of treatment if that seems indicated. Above all, if your breed club sponsors a health registry or research project on seizures or epilepsy in your breed, participate fully in it. New research on epilepsy is being done each year in an effort to determine how it's inherited and ultimately, to design a test that will allow breeders to select against this health defect.
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« Отговор #1 -: 25.06.2011 23:22:56 »

Резултати от изследване на CANINE EPILEPSY NETWORK в Америка

Целта на това изследване е да се определят гените, причинители на това заболяване, за да може чрез разумно развъждане честотата на това заболяване да бъде намалена до минимум.

До 28 януари 2011 г. са били предоставени за изследване 9909 проби, от 108 различни породи, от които засегнати са били 1578 кучета.

Тъй като пробите са подавани на добра воля, честотата на срещане във всяка порода не трябва да се тълкува като показател за честотата на този проблем в рамките на породата, но може да послужи да покаже ангажираността на любителите на тази порода да помогнат на изследователите да решат този проблем.


   Породи                       Изследвани   Засегнати    в %
1  German Shepherd Dog           31           16          51,61
2  mixes/cross-bred dogs         12            6          50,00
3  Other breeds                 155           70          45,16
4  Poodle - Miniature            25           11          44,00
5  Jack Russell Terrier          28           11          39,29
6  Boxer                         13            5          38,46
7  Italian Greyhound             52           20          38,46
8  Silky Terrier                 26           10          38,46
9  Shetland Sheepdog             42           16          38,10
10 Border Terrier               184           70          38,04
11 Dalmatian                    102           36          35,29
12 Canaan Dog                    26            9          34,62
13 Schipperke                    52           18          34,62
14 Pomeranian                    34           11          32,35
15 Bulldog (English Bulldog)     10            3          30,00
16 Golden Retriever              67           20          29,85
17 Cocker Spaniel (American)    133           38          28,57
18 Rottweiler                    14            4          28,57
19 Chesapeake Bay Retriever      87           24          27,59
20 Alaskan (Racing) Husky        11            3          27,27
21 Poodle - Standard            232           63          27,16
22 Pyrenean Shepherd             26            7          26,92
23 Fox Terrier (Wire)            15            4          26,67
24 Spinone Italiano              30            8          26,67
25 Siberian Husky                98           26          26,53
26 Irish Setter                 250           66          26,40
27 Labrador Retriever           308           81          26,30
28 Welsh Terrier                 47           12          25,53
29 German Shorthaired Pointer    63           16          25,40
30 Brittany                      41           10          24,39
31 Petit Basset Griffon Vendeen  78           19          24,36
32 Border Collie                144           35          24,31
33 Collie                       121           29          23,97
34 Weimeraner                    22            5          22,73
35 Great Pyrenees                23            5          21,74
36 Bernese Mountain Dog          19            4          21,05
37 English Shepherd              39            8          20,51
38 Finnish Spitz                 80           16          20,00
39 Beagle                       198           38          19,19
40 Ibizan Hound                  94           18          19,15
41 Dachshund                     84           15          17,86
42 Curly Coated Retriever        75           12          16,00
43 Tibetan Mastiff               25            4          16,00
44 Mastiff                       26            4          15,38
45 Otterhound                   261           40          15,32
46 Newfoundland                  14            2          14,29
47 Great Dane                    30            4          13,33
48 Irish Water Spaniel          310           41          13,23
49 Australian Shepherd         1221          158          12,94
50 Chinook + Chinook cross      304           39          12,83
51 German Pinscher               36            4          11,11
52 English Springer Spaniel     921           99          10,75
53 Welsh Springer Spaniel       243           25          10,29
54 Vizsla                       282           29          10,28
55 American Water Spaniel       266           27          10,15
56 Borzoi                        21            2           9,52
57 Saint Bernard                343           32           9,33
58 Standard Schnauzer           183           17           9,29
59 Pointer                      337           28           8,31
60 Norwich Terrier               94            7           7,45
61 Akbash Dog                    14            1           7,14
62 Anatolian Shepherd Dog        14            1           7,14
63 Field Spaniel                115            8           6,96
64 Greater Swiss Mountain Dog  1247           86           6,90
65 Bloodhound                    73            5           6,85
66 Alaskan Malamute             170            9           5,29
67 Cardigan Welsh Corgi          19            1           5,26
68 Bullmastiff                   21            1           4,76
69 Giant Schnauzer               63            3           4,76
70 Komondor                      48            1           2,08
71 Samoyed                       52            1           1,92

В други породи са включени всички, за които са изпратени по-малко от 10 проби, а именно:
Akita, American Bulldog, Australian Terrier, Basenji, Belgian Laekenois, Belgian Malinois, Belgian Tervuren, Bichon
Frise, Black Russian Terrier, Bluetick Coonhound, Boston Terrier, Briard, Cavalier King Charles Spaniel, Chinese
Crested, Chinese Shar-Pei, Dandie Dinmont Terrier, English Cocker Spaniel, English Setter, English Toy Spaniel
Flat-Coated Retriever, French Bulldog, Irish Wolfhound, Keeshond, Leonberger, Mi-Ki, Nova Scotia Duck Tolling
Retriever, Old English Sheepdog, Papillon, Pembroke Welsh Corgi, Pit Bull Terrier, Poodle-Toy, Portuguese Water
Dog, Saluki, Scottish Deerhound, Scottish Terrier, Small Munsterlander, Staffordshire Bull Terrier, Tibetan Terrier
Whippet
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« Отговор #2 -: 13.12.2011 11:16:35 »

Ето и нещо не български за болестта

Епилепсия

Източник: Ветеринарна клиника Авицена

Епилепсия – заболяване на главния мозък, периодически проявяващо се с пристъпи на припадъци,гърчове,спазми,конвулсии,нарушение на съзнанието, чувствителноста, поведението и други вегетативни прояви.

Епилептичен статус – опасно за живота състояние,съпроводено със загуба на съзнанието и гърчове в продължение на по-вече от 30 минути или повторение на припадъците с интервал до 30 минути без пълно възстановяване на съзнанието.
Причините могат да бъдат вътремозъчни и извънмозъчни, като метаболитни нарушения, хипогликемия, бъречна и чернодробна недостатъчност, енцефалопатия, съдови нарушения, аномалий на развитието,възпалителни процеси, черепно-мозъчни травми, отравяния.
Често страдат кучетата от 6 мес. до 5 год.Заболяването при животни до 2 год,често протича тежко и лечението е малко ефективно.

Епилептичните припадъци се разделят на генерализирани и парциални. Генерализираните могат да бъдат съпроводени с гърчове и с умерено нарушение на съзнанието,със слабо изразени моторни признаци.При кучето е характерна билатерално и симетрично въвличане на мускулите на тялото.Парциалните се характеризират с локалност и асиметрия на моторната актиност, със запазване или не на съзнанието, биват - прости и сложни.

Клиническото проявление на припадъците и гърчовете зависи от локализацията на патологическото разреждане на електрическите заряди и разпространение огнищата на свръхактивност в главния мозък.”Времето на подготовка за припадък” протичащ от няколко часа до няколни дни е характерен с признаци на безпокойство, потребност от движение,стремеж от усъмотяване в ъгъла.Припадането е предшествано от тонични и клонични съкращения на мускулите, фазата на припадъка е съпроводена с нарушение на  съзнанието, слюнотечение, самоволна дефикация и уриниране.Въстановяването е частично с остатъчни явления – полидепсия и полифагия, временна слепота, дезориентация, объркване, паника.
При извършване на рутинните лабораторни анализи , резултатите обикновенно са в норма.

Характера и продължителноста на лечението зависят от честота и тежеста на припадъците. Лечението с антиконвулсни препарати в повечето случай е симптоматическо, а не етиологическо.Класически препарат е фенобарбитала,той при по-младите животни се резорбира по-бързо и дозата е индивидуална.При тежки случай се назначава венозно и диазепам.Рязкото спиране на фенобарбитала може да провоцира повишаване на гърчовата активност.Ако припадъци не се повторят в продължение на 6 мес. антиконвулсивните препарати могат постепенно да се намалят и в продължение на няколко месеца да се отменят.
Активен

Само две неща са безкрайни - Вселената и човешката глупост, като за първото не съм сигурен.
Алберт Айнщайн
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