Tokushukai Medical Group

Treatment of disorder

medical treatment

Cranial Nerve Surgery Disease:Epilepsy

Developed by supernormal excitability of nerve cell.

Epilepsy is a chronic disease which spasm occur repeatedly more than 2 times as brain nerve cell excite super normally. In case there occur sudden onset of consciousness disorder, dyskinesia/impaired sensation and there is epidemical spasm, possibility of epilepsy is high. Nerve cell in the brain is acting with regularly concerted electric signal. But when excessed electric disturbance or supernormal excitability occur, epilepsy may be developed.

Symptoms are various like, convulsion, spasm, feeling foggy, jerking, walk around without consciousness (automatism), impaired vision, impaired sensitivity, abdominal discomfort, psychological symptom. Variety of symptoms appears depend on which range of brain nerve cell produces supernormal excitability.

Eye witness of the spasm is effective for diagnosis.

With sufficient clinical history and to witness the scene of seizure is the most effective thing to diagnose epilepsy (evidence level II, hereinafter evidence level is referred to as “E”). To diagnose epilepsy, at least 2 time of spasm is necessary (Grade B). But in case if the patient, who has diagnosed as general tonic seizures at fist seizure, has anamnestic history of myoclonic-atonic seizure, absence epilepsy and simple/complex partial seizure, epilepsy can be diagnosed even with having one-time seizure (E-III). Interview contents are as follows.

Information by patient/witness
  1. Frequency of seizure
  2. Situation of seizure and inciting cause
  3. Symptoms before and during seizure (physical/mental/consciousness disturbance: reaction of patient, movement of limbs, opening/closing of eye, eye deviation, phonation, color of face, breath, pulsebeat)
  4. Continuance of symptom
  5. Symptom after seizure
  6. With or without external injury, tongue biting or incompetency of urine
  7. Existence or non-existence of Headache or muscle pain after seizure
  8. Age of new-onset
  9. Alteration and transition of seizure type
  10. Last seizure
  11. Relation with awakening and sleep (sleep duration inclusive)
Necessary items for clinical record in addition to the above.
  1. Age of new-onset
  2. Gender
  3. Clinical history (perinatal abnormity, fever convulsion, history of head trauma)
  4. Clinical history of mental disorder, alcoholic drink history, addiction medicine, narcotic substance history
  5. Family history
  6. Social history (academic record, occupation history)

Differentiation of seizure type is inevitable for treatment selection.

For the classification of epilepsy seizure type, International League Against Epilepsy ILAE classification is used. This classification is inevitable for handling a patient, examination, selection of anti-epilepsy agent and selection of surgical treatment.

Symptoms indicating partial epilepsy
  1. Clinical history to be a causal factor of disease
  2. Prognostics
  3. Local movement and sensing stigma at the beginning and during the seizure
  4. Automatism (however, there is a case where absence seizure may be complicated with automatism)
Symptoms indicating idiopathic general epilepsy
  1. Pathogeny from childhood stage to youth stage: pathogeny over 25 years old is the rare case
  2. Set up with sleep deprivation or alcohol
  3. Tonic-clonic seizure or myoclonic-atonic seizure immediately after wake-up
  4. The case where there is no other neurosis symptom and seizure type is absence attack seizure.
  5. Photo convulsive response is observed by brain wave, generalized 3Hz spike-and-slow-wave complex or multiple spike-and-slow-wave complex
Symptoms indicating Symptomatic general epilepsy
  1. Onset age is too young; younger than 1-year, neonatal period/babyhood
  2. Frequent seizure
  3. Mental deficiency or neurotic symptom existed from before pathogeny.
  4. Advancement or regression of neurotic symptom.
  5. Pervasive EEG abnormalities
  6. Abnormal brain morphology

Differentiation diagnosis: easily misdiagnosed disease.

Patients taking visiting the ER office due to suddenly developed loss of conscious, 40 % of them are neutrally mediated syncope/ psychogenic non-epileptic seizure, 29% of them are epilepsy, 7% is cardiac syncope. Characteristics of syncope is that; no change in consciousness fatigue or feeling of malaise after seizure.

Differential Diagnosis (adult)
  1. Faint (neuromodulatory/cardiogenic)
  2. Psychological seizure
  3. Hyperventilation & panic seizure
  4. Cerebral apoplexy, TIA
  5. Acute intoxication, substance withdrawal, alcohol withdrawal
  6. Acute metabolic disease (low blood sugar, tetany)
  7. Acute renal failure
  8. Immediately after head trauma
Differentiation Diagnosis (childhood) and differentiation method
  1. Febrile convulsion: seizure at the onset of fever
  2. Breath-holding spells cyanosis type: after crying bitterly, breathing stop and cyanosis, lost consciousness and faintness followed by generalized seizure.
  3. Breath-holding spells pale type: Suddenly lost consciousness without crying by unexpected incitement.
  4. Convulsiveness at the onset of sleep: short and small convulsiveness at the beginning of sleep, singular/repetitive, unsymmetrical, common at lower limb but happen on upper limb or head as well.
  5. Sleep myoclonus: Occur at all sleeping stage, asynchronous + bilateral symmetric, Occur at body trunk/proximal muscle/distal muscle
  6. Night terror disorder/noctambulant: Screaming/wailing/excitement/fast pulse, one to 10 minutes, suddenly stand-up, walking or running, 1 to 40 minutes, common in age of 4 to 12 years old. Occur in first 1/3 of sleep. Do not awake even trying to be awakened. No memory in oneself. Possible to have had a family.
  7. Benign infantile convulsion: apyretic general unilateral epileptiform. No clinical history. Growth is normal. Normal on brain wave. Onset by 2 years old.
  8. Minor gastroenteritis related seizure
  9. Tic: increased by mental strain. Conscious. Oneself does not recognize the difficulty. No symptom during sleep.
  10. Faint (neuromodulatory/cardiogenic): Vagal reaction like fear or pain or retortion like cough, emiction or swallowing occur at postural change or stand-up. Short in lost consciousness period.
  11. Psychological seizure: Commonly occur under same situation. Do not occur where others have not seen. For accurate diagnosis, brain wave form at seizure is necessary.
  12. Acute metabolic disease (low blood sugar, tetany): Hyponatremia, unilateral epileptiform with hypernatremia, lost conscious with hyperammonemia, unilateral epileptiform
Things indicating generalized tonic seizure and tonic-clonic seizure

Febrile convulsion, Benign infantile convulsion, Minor gastroenteritis related seizure, a part of psychological seizure, acute metabolic disease, sustained cyanosis breath-holding spells

Things indicating loss of consciousness and cataplectic seizure

Breath-holding spells, neurally mediated syncope, a part of psychological seizure, a part of acute metabolic disease, a part of febrile convulsion


Sleep myoclonus, a part of psychological seizure

Diseases indicating peculiar behavior like fear or loitering

Night terror disorder/noctambulant, psychological seizure

This disease is commonly diagnosed by clinical history, symptoms, onset age and brain wave forms. But there are the cases where febrile convulsion, later stage of benign infantile convulsion and part of acute metabolic disease may indicate epileptic seizure waveform so that it is necessary to pay attention for these cases.

Necessary examination for epilepsy diagnosis.

Examination for the diagnosis are as follows.

Brain waveform examination (light stimulation, hyperventilation, sleep)

Sleep activation electroencephalogram (EEG) may increase appearance frequency of epilepsy discharge and to quell normal brain wave so that discharge can easily be interpreted.

Nerve image examination


Polysomnography (Simultaneous video brain wave recording)

It is especially important to differentiate seizure type of frontal lobe epilepsy or temporal lobe epilepsy by means of polysomnography.

Light-sensitive epilepsy which is high in genetic component.

To diagnose Light-sensitive epilepsy where seizure is caused with light stimulation, appearance of photo paroxysmal response; PPR by light stimulation by brain wave examination is necessary. When PPR exist in brain examination, it is diagnosed as Photosensitive epilepsy;PSE. There are potential photosensitive patients who do not notice light sensitive constitution until brain examination is received. Frequency of light-sensitive epilepsy is one out of 4,000 at age of 5 to 40 years old. Hereditary component is high and tonic-clonic seizure combined with spasm.

Juvenile myoclonic epilepsy.

Short time contraction of hamstrings muscle is suddenly occurred and may occasionally generalized. There is no loss of consciousness. It takes about 5 to 10 % of idiopathic generalized epilepsy. It is developed from childhood to youth period and has the following characteristics.

  1. Triggered by broken sleep or alcoholic drinking
  2. Early morning
  3. Short period absence seizure
  4. Brain wave: photo convulsive response, Generalized 3Hz spike-and-slow-wave complex, multiple spike-and-slow-wave complex

Chemotherapy treatment for epilepsy, treatment from 2nd seizure is the basic.

In principle, anti-epilepsy drug is not used at isolated seizure (first time seizure). Anti-epilepsy drug is start using from second seizure. But, in case when there are neurological abnormality, brain wave abnormality or epilepsy family history, start of treatment is considered. Treatment start from the age 65 or over, recurrence rate is getting high after first seizure (66 to 90%). Seizure appearance rate within 5 years from first seizure is about 35%. Recurrence rate within 1 year after the second seizure is 73%. Seizure rate after the start of treatment has a significant difference as shown below for the case where number of seizures before the start of treatment are over 21 times or less 20 times.

For over 21 times, recur at 37%

For less 20 times, recur at 29%.

Chemotherapy treatment should be started as early as possible from second seizure.

Selective drugs
  1. First Choice
  2. Second Choice
Partial epilepsy
  1. Carbamazepine
  2. Phenytoin, Zonisamide
  3. Valproate
Novel drug (generic drug)
  1. Lamotrigine
  2. Levetiracetam
  3. Topiramate

Alteration to generic drug is not recommended when seizure is hold. Because, there are no high-quality evidence which validate the equivalence of therapy using novel drug and generic drug. Regarding the drug alteration, it is reported that the seizure deterioration or side effect appearance may develop.

Generalized epilepsy
  1. Valproate
    • Tonic-clonic seizure Phenobarbital
    • Absence seizure Ethosuximide
    • Myoclonic seizure Clonazepam
Generalized epilepsy

Following to Valproate

* Carbamazepine and gabapentin are not used for idiopathic generalized epilepsy because they may get diseases worse. Benzodiazepines drugs or Lennox-Gastaut Syndrome may get tonic seizure worse. They can be seen on every anti-epilepsy drugs, but Valproate is listed as E-1 for teratogenesis and newborn IQ disability.

Large-size research says that in the Progressive Myoclonus Epilepsy;PME (Unverricht-Lundborg disease), Phenytoin may hold the seizure itself but life prognosis may get worse (E-2), and cerebellar ataxia is getting worse.

Chemotherapy effect judgement and period of duration.

Deduction of anti-epilepsy drug is considered after the seizure disappearance in 2 to 5 years. However, in juvenile myoclonic epilepsy, recurrence rate is high.

Selective drug for the case where mental symptom exists.

Anti-epilepsy drug is divided into GABA actuated drug which has anti-anxiety action and manic state inhibitory effect, and glutamic acid-based inhibitory drug which has antidepressant action and anxiogenic effect.

GABA actuated drug

Barbital acid, Benzodiazepines drug, Valproate, gabapentin, Topiramate,

Glutamic acid-based inhibitors

Lamotrigine, Levetiracetam
Zonisamide has both effects.

Drugs with emotional stabilization effect

Valproate, Carbamazepine, Lamotrigine

* Ethosuximide, Zonisamide, Primidone, High Dosage phenytoin and Topiramate may raise the acute psychological symptom. Benzodiazepines anti-epileptic drugs may cause the acute psychological symptom at abstinence. As the side effect of anti-epilepsy drugs, they are depressed state or deterioration of mental function by phenobarbital, depressed state by Ethosuximide, Carbamazepine, Clonazepam, Zonisamide and Valproate, and Hypomania State. So that having caution to them is important.

Drug selection for the complicated case with renal and kidney function.

Anti-epilepsy drug is divided into GABA actuated drug which has anti-anxiety action and manic state inhibitory effect, and glutamic acid-based inhibitory drug which has antidepressant action and anxiogenic effect.

hepatic metabolism

Valproate, Phenytoin, Carbamazepine, Phenobarbital, Benzodiazepines

renal metabolism

Gabapentin, Levetiracetam

liver kidney metabolism

Topiramate, Lamotrigine


Valproate, Carbamazepine

Cardiac Communication System abnormalities

Phenytoin, Carbamazepine

cognitive function decline

Phenobarbital, Zonisamide, Carbamazepine

Parkinsonism-dementia complex


Phenytoin effect in hypoalbuminemia may increase.

Drug selection for high-aged person.

Partial seizure without complicated disease

(1) Carbamazepine, (2) Lamotrigine, (3) Levetiracetam, (4) Gabapentin

Partial seizure with complicated disease

(1) Levetiracetam, (2) Lamotrigine, (3) Gabapentin

Generalized Epilepsy without complicated disease

(1) Lamotrigine, (2) Valproate, (3) Levetiracetam, (4) Topiramate

Should pay attention for combined medicine at chemotherapy treatment.

Drugs which lower the epilepsy threshold are listed below.

Chemotherapy for refractory epilepsy.

Definition of refractory epilepsy is the status where appropriate anti-epilepsy drug, more than 2 to 3 kinds of drugs combined and with enough volume, are taking more than 2 years, but still seizure has not been inhibited for more than one year so that daily life is disturbed much.

The definition of social refractory epilepsy is the status where “seizure inhabitation cannot be achieved by over 2 years adequate chemotherapy treatment”. Inhibition rate of antiepilepsy drug under normal chemotherapy treatment are; 1st antiepilepsy drug 47%, second is 13%, third or combination case of more than 2 drugs is just 4%. Therefore, when seizure inhibition cannot be recognized with more than 2 drugs chemotherapy is differentiated to refractory epilepsy. Application reference for surgical treatment is the case where more than one-time seizure occurs in monthly average under the chemotherapy, and daily life is interfered. In the Road Traffic Act, Driving License cannot obtain unless seizure is inhibited for more than 2 years. Besides, if there is partial seizure more than 2 times a year, second grade of Health and Welfare Handbook for mentally handicapped is applicable.

Variation of adult refractory epilepsy.

In adult epilepsy, temporal lobe epilepsy with hippocampal sclerosis is the most intractable one. (case where seizure is inhibited for more than 1year is 11%), but surgical result of selective hippocampal amygdala Removal or resection of the temporal lobe hippocampal amygdala are in good treatment results with cure rate of 85%.

With the imaging examination, cerebrovascular disease, brain malformation, tumor, hippocampal sclerosis, after encephalitis/encephalopathy, and general disease are checked. Symptomatic generalized epilepsy by dentatorubro-pallidoluysial atrophy; DRPLA or epilepsy which cannot inhibit by childhood developed Lennox-Gastaut syndrome, are easy to become refractory one.

When spasm continues more than 2 years, surgical operation is inevitable.

For the epilepsy where seizure cannot be inhibited for more than 1 year even though adequate 2 or 3 combined drugs with enough blood concentration has been administrated for more than 2-years, surgical operation is considered.

Brain Surgery Committee in International Epilepsy Committee considers the surgery within 2 years of incidents, because underdeveloped may happen for children. Other than the disappearance of epilepsy seizure and its associated improvement of QOL, it is known that the psychomotor development is improved with children. Also, absolute mental retardation or existence of psychological disorder will not be the reason for the exclusion reference of surgical accommodation. Although numbers of seizure are less, surgical operation is considered for symptomatic epilepsy with intracerebral lesion, epilepsy with the fear of external injury like rollover and epilepsy which causes disadvantage on social life like work. However, symptomatic epilepsy caused by gene abnormality, such as dentatorubropallidoluysial atrophy (DRPLA) and symptomatic epilepsy caused by progressive disease are not the target of surgery operation.

Five epilepsy syndromes subject to surgical treatment.
  1. mesial temporal lobe epilepsy MTLE
  2. Partial epilepsy where organic disease is detected
  3. Partial epilepsy which organic pathological change are not recognized.
  4. Partial epilepsy by broader pathological change on unilateral hemisphere
  5. refractory epilepsy with astatic seizure

MTLE-HS where hippocampal sclerosis (HS) is contained, is the best adapted for surgical treatment, and significant seizure disappearance is expected. In the Catastrophic epilepsy, there exist a partial epilepsy with broader pathological change on unilateral hemisphere. But this is developed in infancy period then paralysis or involution of psychomotor seizure is raised by drug resistance so that it is recommended to have surgical operation at early stage.

Accommodation of intracranial electroencephalogram recording and its effectiveness.

Intracranial EEG recording is the invasive examination, but it is useful to determine epileptogenic zone in neocortical epilepsy. In mesial temporal lobe epilepsy in case when hippocampal observation by MRI and brain wave observation are not contradictive each other, intracranial EEG recording can be excluded.

Brain wave recording using subdural electrode has the 10 times of space resolution accuracy. Permanent complication disease is 1.5%, and they are caused by bleeding in the brain and infection. Surgical treatment for mesial temporal lobe epilepsy (58%) is superior than medical therapy (8%) (Grade A).

Surgical treatment result for neocortical epilepsy is; temporal lobectomy (66%), Occipital and parietal lobectomy (46%), frontal lobectomy (27%), multiple subpial transection (16%), and corpus colostomy (35%). Engel classification is used for postoperative seizure outcome assessment.

Temporal lobectomy

In case of dominant hemisphere, it can cut maximum 4.5cm from top edge of temporal lobe, and in case of non-dominant hemisphere, able to cut up to maximum 6cm.

Selective anterior temporal lobectomy

Inside observation of lateral cerebral ventricle: Hippocampus forms the floor of inferior horn of lateral ventricle, and amygdala forms a part of lateral ventricle inferior horn upper wall facing to hippocampus.

After suction removal of uncinate gyrus: Posterior cerebral artery, anterior choroidal artery and oculomotor nerve are observed from brain ventricle side through buffy coat wrapped around uncinate.

Cutoff of hippocampus: With cutting off anterior side of hippocampus, hippocampus can be cutoff to inferior choroidal point which is the entrance part of anterior choroidal artery into brain ventricle.

Peel anterior side of para hippocampal gyrus off: Carefully remove buffy coat on the anterior side of para hippocampal gyrus, then peel para hippocampal gyrus off under buffy coat to external side as much as possible.

Cut off hippocampal formation dorsal: Cut hippocampal formation dorsal at innominate groove between collateral eminence and hippocampal formation.

Extraction of Hippocampus / Extracted Hippocampus and hippocampal gyrus

Brain surface after hippocampus extraction: Epidemical damage on lateral cortex of frontal cortex (*)and temporal cortex(*) has not recognized.

Lateral Approach

Generalized epilepsy remarkable efficiency: 40 to 60% With cutting Left/right hemisphere off at callosum to prevent both cortical substance from generalizing to epilepsy seizure. To prevent acute withdrawal syndrome, corpus Callosotomy will commonly perform as secondary surgery so that one month later from front side 2/3 callosum cut off surgery, rear side 1/3 corpus Callosotomy is performed.

Enlargement of surgical area on corpus

lamina of translucent septum

splenium of corpus callosum cut off

Confirm Splenium of corpus callosum cut off.

Lateral Approach

(1) There are Lateral approach (Trans-ventricular hemispherotomy) and (2) vertical approach available. Lateral approach consists with four common technics; Cutting of encapsulated fibers, Resection of inside temporal lobe structure, corpus Callosotomy, Frontal lobe Horizontal Fiber cutting. (1) Resection of inside temporal lobe structure, (2) Cutting of encapsulated fibers, (3) Frontal lobe Horizontal Fiber cutting, (4) Trans ventricle callosum separation, (5) Separation of remaining falling fibers.

Vertical Approach
  1. Cut off line of hypothalamic outer edge
  2. Access route to Ventricle horn (trans cingulate)
  3. Separation of Callosum

Vagus nerve stimulation equipment implantation, VNS implantation

Surgery available at only epilepsy surgery department in the epilepsy authorized facility.