CIRURGIA DE EPILEPSIA

Elza Márcia T. Yacubian

Professora Livre-Docente do Departamento de Neurologia e Neurocirurgia da Universidade Federal de São Paulo

 

O nascimento da cirurgia de epilepsia

 

Apesar de ainda pouco conhecida, a cirurgia de epilepsia teve um início muito antigo e sólido. Originada da necessidade de tratar indivíduos que continuavam apresentando crises epilépticas a despeito do tratamento com fármacos antiepilépticos, a primeira cirurgia de epilepsia após experimentos de estimulação elétrica em cérebros de animais que permitiram a localização das funções motoras nos hemisférios cerebrais. Dois jovens e desconhecidos alemães, Eduard Hitzig (1838-1907) e Gustav Fritsch (1838-1927) demonstraram que a estimulação elétrica do córtex cerebral de cães produzia contração de músculos do lado oposto ao hemisfério estimulado o que sugeria que o movimento tinha origem no córtex cerebral. Estes pesquisadores demonstraram ainda que a estimulação por correntes elétricas de maior intensidade determinava crises epilépticas.  Seu contemporâneo, o pesquisador britânico David Ferrier (1843-1928) confirmou estes achados do cérebro de macacos. Na última década do século 19 os mesmos tipos de experimentos foram reproduzidos por outros, entre eles o médico Victor Alexander Horsley (1857-1916), famoso neurocirurgião londrino, que reconheceu a vantagem da localização cerebral dos movimentos corporais como uma forma de determinação dos limites da área a ser removida cirurgicamente de cérebros doentes. Em 25 de maio de 1.886 realizou a cirurgia de James B., seu paciente escocês de 22 anos que sofrera um afundamento ósseo com compressão do hemisfério esquerdo aos 7 anos e apresentava eventos epilépticos intratáveis desde 15, extremamente freqüentes de até 3.000 crises epilépticas em uma única quinzena, quase sempre com as mesmas características, começando usualmente na perna direita, propagando-se então para o braço direito e ascendendo para a metade direita da face. A remoção de uma cicatriz muito vascularizada no local da antiga lesão bem como do tecido ao redor numa profundidade de 2 cm., resultou no controle completo das crises. O segundo paciente operado por Horsley foi outro jovem de 20 anos que havia apresentado 1.945 crises em 14 dias, cujas características eram quase sempre as mesmas. Elas se iniciavam com espasmos do polegar e indicador esquerdos seguidos pelo punho, cotovelo e ombro que se tornavam fletidos; em seguida havia espasmo facial e o paciente perdia a consciência. A cabeça e os olhos se voltavam para um lado e a perna esquerda tornava-se tensa. Estas crises freqüentemente eram seguidas por paralisia do braço esquerdo. Baseado nestes dados Horsley postulou que seu paciente apresenta uma lesão irritativa de natureza desconhecida, situada na parte do cérebro responsável pelos movimentos do lado esquerdo do corpo e após a abertura do crânio encontrou uma lesão de natureza tuberculosa cuja remoção tornou seu paciente livre de crises. Estes procedimentos extirparam as lesões que originavam descargas epilépticas e causavam as crises.

Entre 1894 e 1898 foram publicadas sete teses de doutorado sobre o assunto na Áustria, Inglaterra, França, Alemanha, Itália, Holanda, Polônia, Rússia e Estados Unidos. Em 1898 houve um relato incluindo 146 casos e este “entusiasmo cirúrgico” foi atribuído aos avanços na localização das funções corticais.

 

Indicações da cirurgia de epilepsia

A cirurgia cerebral para epilepsia tem sido realizada desde então e para ser um candidate cirúrgico, o indivíduo precisa ter crises epilépticas documentados, as quais se mostram persistentes a despeito do tratamento adequado com fármacos antiepilépticos. Há necessidade da documentação inequívoca de que as crises epilépticas se originam numa parte bem definida do cérebro cuja remoção não promoverá dano em funções cerebrais importantes, como fala, memória, movimentos ou visão. Patients with disabling complex partial seizures, with or without secondarily generalized seizures, who have failed appropriate trials of first line antiepileptic drugs, should be considered for referral to an epilepsy surgery center, although criteria for failure of drug treatment have not been definitely established (level A rating) Patients referred to an epilepsy center for the reasons stated above who meet established criteria for an anteromedial temporal lobe resection and who will accept the risks and benefits of this procedure, as opposed to continuing pharmacotherapy, should be offered surgical treatment (level A rating).3 Surgery for epilepsy is a delicate, complicated operation. It must be performed by a skilled, experienced surgical team. It is usually done at special medical centers that treat patients with epilepsy rather than at local hospitals. In addition to operations that remove a small part of the brain where seizures begin, other procedures may be done to interrupt the spread of electrical energy in the brain. People who are going to have epilepsy surgery may have several special tests first. In some cases, electrodes have to be implanted in a separate operation to locate seizure sites deep in the brain. Sometimes these tests take days or even weeks to complete. In some cases, the patient may be awake during part of the operation. This is not usually the case with small children. This is possible because the brain does not feel pain. Having the patient awake helps the doctors make sure that important parts of the brain are not damaged. Afterwards, some seizure medications may have to be continued, usually for a year or two. Then, if no further seizures occur, the medicine may be slowly withdrawn. At this point, chances of living free of seizures and free of medication are good. However, many people will have to continue with medication and some do not benefit from surgery

 

EEG evaluation

The most useful test in epilepsy diagnosis is the EEG. An essential mistake is to place too much value on an isolated individual interictal recording. Assuming that a normal finding from the interictal scalp electrode EEG precludes the diagnosis of epilepsy is erroneous. The presence or absence of epileptiform discharges is highly variable, has no relationship to seizure frequency (for most epilepsies), and may be affected by antiepileptic drugs (AEDs). Thus, EEGs may need to be repeated several times before epileptiform discharges are observed. By definition, "epileptiform discharges" are interictal patterns that include spikes, spike-and-slow-wave complexes, sharp waves, and sharp-and-slow-wave complexes. The reader should refer to the second international glossary of EEG terms for precise definitions.⁸

When the waking scalp EEG fails to demonstrate evidence of epilepsy, but the diagnosis is still suspected, a sleep EEG is recommended. Epileptiform discharges commonly activate during non–rapid eye movement sleep in some epilepsies. On fewer occasions than in the past, sphenoidal and additional extracranial electrodes are used to help reveal epileptiform (interictal) and ictal discharges.⁹

Although the standard scalp EEG is helpful in making a diagnosis of epilepsy, it is not usually used when the physician makes major surgical decisions. This is because the distribution of interictal EEG discharges may not correctly localize epileptic foci. This error occurs for several reasons. First, discharges can be multifocal, although one focus can be the origin of all seizures. Further, because the EEG consists of volume-conducted potentials that originate over a relatively large area of cortical gray matter, some discharges can shift apparent location within or between hemispheres, and others may appear widely or even diffusely over the scalp. In addition, to obtain the most accurate data possible, recording sufficient numbers of the patient's typical seizures is important.

Like interictal discharges, ictal discharges vary somewhat. Also, more than one seizure focus or psychogenic or physiologic nonepileptic seizure may be found when numerous episodes are recorded.^10,11 The latter may greatly affect a decision to proceed with surgery. Therefore, all surgical candidates should undergo long-term video-EEG monitoring prior to surgery to record several typical seizures.

Features of the scalp EEG ictal discharge, other than just location, can be helpful in the presurgical evaluation. For example, the authors reported that the frequency of the initial ictal discharge in the scalp EEG correlates with the degree of hippocampal pathology in temporal lobe epilepsy.¹²

Neuropsychological testing

Neuropsychological testing, also known as neurocognitive testing, is the process of empirically testing an individual's functioning across a variety of cognitive domains, including attention, concentration, language, visuospatial skills, verbal and visual memory, and executive abilities (ie, problem solving, organization, strategic planning), as well as personality and emotional functioning. Neuropsychologists use a variety of standardized tests to assess all areas of cognitive functioning. An individual's performance on these standardized tests is then analyzed using normative data, and their performance is then compared with their peers and with what is expected based on estimates of their premorbid level of cognitive functioning. Patterns of cognitive strengths and weaknesses then provide information about brain-related deficits in cognitive functioning.

Well established is the idea that performance on specific neuropsychological tests is subserved by various areas of the brain, thus providing lateralizing and localizing information about brain functioning. For example, a right-handed individual's performance on verbal memory tests (ie, story memory, verbal paired associates learning, and list-learning tasks) is largely subserved by left mesial temporal structures.¹³ Similarly, a right-handed individual's performance on visual memory tests (ie, figural memory and complex figure memory tasks) is largely subserved by right mesial temporal structures. Thus, an individuals cognitive strengths and weaknesses on neuropsychological testing can indicate areas of brain dysfunction, which provides additional information that can help localize an epileptogenic focus.¹⁴

Additionally, an individual's cognitive strengths can provide information about possible cognitive risks involved in undergoing a neurosurgical resection to treat medically-intractable epilepsy because a risk of increased memory deficits after resection of mesial temporal structures exists.¹⁵ Routinely, all epilepsy surgical candidates undergo extensive neuropsychological testing. Neuropsychological testing is tailored to best assess the type of epilepsy with which each individual presents, often focusing heavily on cognitive functioning that has likely been most affected by a hypothesized epileptogenic focus. As a result, testing is often tailored to uniquely assess the cognitive strengths and weaknesses for each individual and can vary across individuals.

Neuropsychological testing can also be used for nonoperative or postoperative epilepsy patients to assess their level of cognitive functioning in order to assist with vocational and cognitive rehabilitation in the context of their neurological disorder.

Intracarotid amobarbital (Wada) test

The intracarotid amobarbital test was developed by Jun Wada to preoperatively determine which hemisphere contains language function. Although this continues to be a use of the Wada test, functional MRI for language now provides a noninvasive way to more accurately lateralize and localize language functioning. The primary use of the Wada test is to assess language lateralization and the ability of the contralateral mesial temporal structures to support memory postoperatively when AMTR is being considered to treat medically-intractable epilepsy.

The procedure is conducted by individually cannulating each internal carotid artery. After contrast arteriography verifies that blood flows to the corresponding hemisphere and not to the brainstem or contralateral side, a dose of sodium amobarbital (sufficient to impede hemispheric function) is injected. If the drug produces a contralateral hemiparesis, function of that hemisphere is assumed to be minimized.

Language lateralization is determined by conducting a comprehensive screen of various components of language, including expressive language, receptive language, naming, repetition, and complex syntactical comprehension. If an individual is able to engage in all aspects of language while they demonstrate hemiparesis, language function is assumed to not be represented within that hemisphere. Assessing a variety of aspects of language is important because some individuals possess a bilateral representation of language, such that some aspects of language are subserved by one hemisphere while other aspects of language are subserved by the contralateral hemisphere.

Memory functioning is assessed by presenting the patient with visual and auditory items (often using multiple sensory modalities to maximize the chance of encoding) while the hemisphere is anesthetized. Following recovery of hemispheric function, which is confirmed by return of gross and fine motor function, as well as language if possible, the patient is then tested for their free, cued, and recognition recall of the items with which they were presented during anesthetization. If the patient is able to accurately recall 75% of the items presented to them during anesthetization, that provides evidence that the contralateral hemisphere should be able to support memory after ATMR of the hemisphere that was anesthetized.

If the patient is unable to accurately recall a sufficient number of items, that information provides evidence that the patient may experience significant memory difficulties postoperatively. Importantly, patients should undergo neuropsychological testing prior to undergoing a Wada procedure, because that testing provides important information about their baseline level of memory functioning and more accurately informs the results of the Wada test.

The deficiencies of this evaluation for memory function directly relate to the multiple problems of targeting a drug effect to specific brain structures via cerebral blood flow. Injection of a drug into the internal carotid artery does not assure drug effect in the basal temporal area in general or the hippocampal region specifically (an area that subserve memory function). This is due to variations in the direct blood supply to the hippocampus and inequalities in delivery when the drug is injected into the blood stream.

Intracranial EEG recordings

Intracranial EEGs recordings, also known as chronic electrocorticography (ECoG) is an invasive procedure that is performed when noninvasive presurgical evaluation has not led to definitive localization of a seizure syndrome and surgical plan. The presurgical team, which includes a neurosurgeon, neurologist, neuropsychologist, social worker, and neuroradiologist, considers all previous accumulated data to determine an appropriate strategy for placement of intracranial electrodes. Any combination of intracranial strips, grids, and/or depth electrodes may be tailored to answer the specific questions posed by the case history and presentation specific to that particular patient, depending on the needs of the patient, experience of the monitoring team, and resources available for use.

The following are examples of instances that may require invasive intracranial monitoring:

• Seizures are lateralized but not localized (eg, a left-sided, widespread frontal-temporal onset).
• Seizures are localized but not lateralized (eg, ictal EEG patterns that appear maximally over both temporal lobes).
• Seizures are neither localized nor lateralized (eg, stereotyped complex partial seizures with diffuse ictal changes or initial changes obscured by artifact).
• Seizure localization is discordant with other data (eg, EEG ictal scalp data discordant with neuroimaging [MRI, PET, SPECT/SISCOM, MEG] or neuropsychological data).
• Relationship of seizure onset to functional tissue must be determined (eg, seizures with early involvement of language or motor function).
• Relationship of seizure onset to lesion must be determined (eg, dual pathology or multiple intracranial lesions).
• Seizures are clinically suspected, but video-EEG is inadequate for defining them (eg, simple partial seizures with no detectable scalp EEG ictal discharge or suspected epileptic seizures with unusual semiology that suggests psychogenic seizures [pseudo-pseudo seizures]).¹⁶

Invasive intracranial monitoring is a diagnostic procedure, designed to identify the site of ictal onset of seizures. Intracranial electrodes are reserved for the most difficult of cases; therefore, one risk of surgery is that the study will end up with a nondiagnostic result. The onus is on the surgeon to question where electrodes should be placed based on the presurgical information available and to consider what other alternative diagnosis should be included or excluded to obtain the best possible electrode placement. The concept that epilepsy consists of a focus that can be removed has evolved into a more unified theory in which the neural network, environment, genetic predisposition, and epileptogenic substrate all must be considered during the evaluation of the patient with epilepsy, if surgery is to be effective.^17,18

 

 

Surgery Types: Benefits and Risks

All epilepsy surgery involves the brain. The operations generally involve removal of epileptogenic tissue from the area where seizures arise or interruption of nerve pathways along which seizure impulses spread.

Lobectomy and Cortical Resection

The most common form of epilepsy surgery is a lobectomy or cortical resection. With recent refinements in diagnostic methods, the procedure is now available to more people. It is estimated that approximately 30 percent of persons with partial epilepsy have seizures that are not well controlled with medications and could benefit from this surgery. All or part of a left or right lobe may be removed surgically. These areas of the brain are common sites of simple and complex partial seizures, some of which may secondarily generalize. Seizures in the temporal, parietal, frontal or occipital lobes may be treated surgically if the seizure-producing area can be safely removed without damaging vital functions.

Hemispherectomy

The operations described above usually remove a relatively small area of the brain. However, when a child has Rasmussen’s encephalitis, a rare, progressive disease affecting one whole hemisphere of the brain, a hemispherectomy to remove all or almost all of one side of the brain may be performed. While it seems impossible that someone could function with only half a brain (the other side fills up with fluid), children manage to do so because the half that remains takes over many of the functions of the half that was removed. Weakness on the side opposite the operation will continue, however. Hemisperectomies may also be performed when children are born with conditions that cause excessive damage to one side of the brain, such as bleeding in the brain prior to birth.

 

Surgical and Social Outcomes

Surgical Outcomes

Most surgery patients stay on antiepileptic medications for one to two years after the operation. Some will have to continue with medication indefinitely for the best outcome.

According to the National Institutes of Health, the success rate of lobectomies or cortical resections (no seizures with loss of consciousness) is between 30 and 70 percent, depending on the area removed. Some centers report higher rates. Brief sensory changes (auras) may continue for some years afterwards. The risk of death to lobectomy patients is less than 2 in 100. Complications occur in about 4 of every 100. These may include partial loss of vision, motor ability or speech. Infection or temporary swelling of the brain may also occur.

Among corpus callosotomy patients the risk of major or minor complications following surgery is around 20 percent. Atonic seizures (drop attacks) generally improve. Other generalized seizures may stop or happen less often. Partial seizures are likely to continue and may even get worse. Centers which perform hemispherectomies report good outcomes. However, there are more risks with this operation than with any other types of epilepsy surgery, and there will be permanent weakness on the side opposite the surgical site. Multiple sub-pial transection has limited data on outcomes.

Social Outcomes

Although seizures may be greatly reduced or totally controlled following surgery, a number of patients report periods of depression during the adjustment period and it appears that the greatest benefit accrues to those whose seizures are completely controlled. Postsurgical studies of patients’ employment and quality of life show the greatest gains among those who had some employment history prior to the operation and among those whose seizures were completely controlled.