DIAGNOSTIC AND THERAPY MISTAKES IN CHILD EPILEPTOLOGY

ABSTRACT: 

Diagnostic and therapy mistakes in child epileptology could be made by the physician, or they could occur as a result of technical incapability. Also, patients and their parents may lead to them, as well. Therefore it is essential for the physician practitioner and pediatrician, as well as for the epileptologist to be aware of all possible mistakes in order to correctly diagnose epilepsy in children and prescribe possible continual antiepileptic therapy. Number of procedures and various technologies are suggested to be used in order to reduce diagnostic mistakes in child epileptology. Diagnostic procedure is clearly defined, from recognizing epileptic seizure, differentiating types of seizures, to syndromic diagnosis of epilepsy. Unfortunately, all these precautions slowly lead to reduction of diagnostic mistakes in child epileptology, but still there is no reliable way to avoid them completely. Avoiding diagnostic mistakes in child epileptology provides children the best possible treatment known among available therapeutic possibilities.

DIAGNOSTIC AND THERAPY MISTAKES IN CHILD EPILEPTOLOGY

Epilepsy occurs in one in 200 children of the general population, as a chronic neurological disease characterized by unprovoked seizures, expressed as transient clinical symptoms and signs of abnormal excessive, synchronous neural brain activity.(1, 2, 3) In light of neurophysiological knowledge, it could actually be defined as a tendency for epileptic seizures.(4) There is no reliable diagnostic test that quickly and easily diagnoses epilepsy in children.

In accordance with: the fact that seizures them-selves are rarely directly observed by a physician who diagnoses, and capabilities of available diagnostic technology for determining between epilepsy seizures and similar events, anamnesis is still of outmost im-portance for the initial diagnosis of epilepsy in children.) In nearly 90% of patients’ epilepsy could be diagnosed by taking sufficiently detailed and accurate medical history. Lack of taking detailed and accurate history of seizures, as well as personal data and family history, is the most common cause of diagnostic mistakes in child epileptology.(6, 7)

It is the best if the family can provide video foot-age of seizures themselves. Observation and precise de-scription of symptoms and signs of seizures in a child is almost art. In most children it is impossible to clearly identify senzory symptoms, based on the observed be-havior of the child, and therefore it is necessary to draw information from the child. In order to obtain accurate information from a child, questions about unrelated problems (symptoms and signs) before the seizure, must always be clear and specific so, the child will not link those to the seizure itself, and only than very de-tailed questions about the seizure should be asked. A large number of children are not able to describe and define their symptoms because of fear, lack of verbal expression, intellectual deficit, or other reasons.

After diagnosing the seizure as epileptic seizure, it is necessary to define the type of seizures and epileptic syndrome, using the standard system and terminology, which is not always possible to do in children. In order to diagnose epilepsy in children, it is necessary to have practical approach, and apply the dynamic aspect of the diagnostic procedure. Syndromic diagnosis of epilepsy defines short-term and long-term therapeutic efficacy and prognosis, as well as the nature and genetic attribute of the disease. In relation to the definition of epileptic seizures, general and symptomatic diagnosis of epilepsy, syndromic diagnosis has significant advantage, because of all defining features of the syndrome, it eliminates the possibility of unexpected morbidity, due to poor catego-rization and thus eliminates the possibility of unexpect-edly poor therapeutic response and outcome.

DIAGNOSTIC PROCEDURE MISTAKES IN CHILD EPILEPTOLOGY

Diagnostic procedure mistakes in child epileptol-ogy could be various:

TOTAL MISTAKES:

• Completely miss-diagnosing epilepsy, or fail-ing to diagnose in general (for not recognizing seizure as an epileptic seizure)
• Correctly but delayed diagnosing epilepsy, (because of the patient, or previous error or lack of implementation of diagnostic procedures)

PARTIAL MISTAKES:

• Incorrectly diagnosing the type of epileptic seizures or epileptic syndrome, while correctly diagnosing epilepsy, this often affects therapy and prognosis,
• Failure to recognize the potential complica-tions of epilepsy and epileptic syndromes (psychomotor retardation in development, West syndrome, continu-ous spike-wave activity during slow-wave sleep …),
• Failure to recognize the underlying disease that causes seizures, not epilepsy clinical manifesta-tion, but symptomatical seizures that are part of un-derlying disease, (Hypoxic ischemic encephalopathy, hypoglycemia, hypocalcaemia or other electrolytic disorder, Rey syndrome, various gene and enzyme neurodegenerative diseases),
• Failure to recognize medication as the main cause of illness (abuse of drugs, stimulants and nar-cotics…),
• Failure to recognize other diseases patient has, that affect epilepsy (neurofibromatosis, tuberous sclerosis,…),
• Failure to recognize other diseases patient has, which have no direct connection nor do they di-rectly affect epilepsy,
• Failure to disclose the underlying disease complications, or potential complications that can develop during treatment of the underlying disease (Cognitive deterioration with progressive epileptic syndrome, loss of vision and/or hearing in neurofi-bromatosis, .. )
• Failure to consider side effects of therapy, which may aggravate the situation or lead to the oc-currence of other disorders (leucopenia, thrombocy-topenia, pancytopenia and bone marrow aplasia, liver lesions, allergic and idiosyncratic reactions,…).

MOST COMMON DIAGNOSTIC MISTAKES IN CHILD EPILEPTOLOGY

Common conditions, even perfectly normal phe-nomenon, a form ofbehavior in children may resemble the clinical seizures, and conversely, different types of seizures in children with clinical manifestations that cannot differentiate from the manifestation of many other diseases.

Diagnostic mistakes in child epileptology have very significant consequences, such as:

• Introduction of antiepileptic therapy (AET) to healthy children, who were wrongly diagnosed with epilepsy,
• Failure to introduce specific therapy (some-times necessary for survival) for the underlying disease (meningitis, encephalitis, electrolyte disturbance.. )
• Failure to introduce AET and allowing recur-rence of seizures in children whose epilepsy remained unrecognized and to whom the continuous therapy was not introduced.(8, 9)

In children, the most common differential diagnostic dilemma is between seizures and paroxysmal nonepileptic events (fits), syncope (faints) and psy-chogenic caused seizures (funny turns).(10,11) Given the overlap of their symptoms, the presence or absence of isolated signs and symptoms can not be accepted as a confirmation or denial of the diagnosis. Clinically, differential diagnosis can be set only when the individual clinical event completely follows known clinical characteristics, with quantity, quality, localization, the way of expression, initiation, sequence chronology, course, speed, progression and duration.(12, 13)

PAROXYSMAL NON-EPILEPTIC EVENTS DIAGNOSED AS EPILEPSY

Non-epileptic seizure, as a descriptive term, is a term that is used for various non-epileptic parox-ysmal events that are not epileptic seizures, but re-semble them. 20-30% of children with non-epileptic paroxysmal events are misdiagnosed with epilepsy, and about 30% of children with epilepsy also have non-epileptic paroxysmal events, which complicates and delays diagnosis up to 9 years, according to the study of de Timary.(14, 15) Such errors are extremely expensive (diagnostic procedures and AET) and are a direct threat to the health of child.

Physicians often decide to introduce the AET when not able to differentiate epileptic from nonepileptic seizure, given that epilepsy is a potentially more serious dis-ease than nonepileptic seizure, with the following expla-nation: “It is a lesser mistake to treat serious condition, than to delay it’s treatment’. Often in situations when a seizure control is not achieved, the AET is changed, rather than to re-consider and review the diagnosis of epilepsy. It is much more difficult to diagnose so-called minor seizures (focal, and myoclonic absences) than gen-eralized tonic-clonic seizures. Short myoclinic seizures mild apsances mild and simple and even complex focal seizures in children are often very difficult to tell apart.

Differential diagnosis of epilepsy in children en-compasses all consciousness and alertness disorders, changes in mental function, collapse, sensory and/or various expressions of motor phenomena up to gen-eralized tonic-clonic seizures, which can all be part of clinical presentation of epileptic seizures. Sometimes, for trained physician, who is familiar with seizures symptoms, it is easy to diagnose, if given complete seizure auto and hetero anamnesis data. Unfortunately even the best educated epileptologists are often un-able to reliably diagnose epilepsy in children, because of seizure’s atypical clinical expression, incomplete or inadequate and hetero anamnesis data and overlap of clinical signs and symptom seizures themselves.

Generally nonepileptic seizures could be divided into: physiological or organic and psychogenic nonepileptic seizures.(16)

ORGANIC NON-EPILEPTIC SEAZURES make a very wide clinical spectrum that includes ev-erything from normal phenomenon (hipnagogic con-vulsions, hallucinations, illusions, ..) to a number of abnormal paroxysmal phenomena, whether as a result of disruption of brain function and/or consequence of systemic disorders (affective respiratory spasms, avoided sudden infant death syndrome, collapse, syn-cope, dizziness, instability, benign paroxysmal vertigo, cyclic vomiting, migraine, stroke, transient ischemic seizure, recurrent abdominal pain, gastro esophageal reflux, kinetosis, night terrors, somnambulism, rapid eye movement sleep, hyperekspleksia, non-epileptic myoclonus, ataxia, tic, staring spells, including Munchausen syndrome). (17, 18, 19, 20, 21)

Most common organic nonepileptic seizures in children are: SYNCOPE, which is often associated with myoclonic jerks, brief convulsive jerks, (convulsive syncope) and bulbous deviation short automatisms, which significantly complicate the differential diag-nosis of syncope and epileptic seizures.(22) Seizures occur in 70-90% nonkardiogenic syncope. Epileptic seizures can be triggered syncope, as anoxic epileptic seizures occur significantly more often in children and adolescents, because usually only epileptic seizures are observed in them, and that compromises the diagno-sis.(23) RESPIRATORY AFFECTIVE SPASMS as a form of controlled neural syncope with prolonged expiratory apnea, can also induce prolonged clonic epileptic seizure with features and myoclonic absences, therefore the diagnosis is extremely difficult.

STARING SPELL is common non-epileptic paroxysmal event in children and adolescents which is difficult to differentiate from absence and the focal seizures. During episodes of ‘staring speli’, which is a clinical manifestation of epileptic seizure, heart rate increases by 30% in 97%.(24)

PSYCHOGENIC NONEPILEPTIC SEI-ZURES are rare in pediatric age group. The most common are convulsive psychogenic nonepileptic sei-zures in adolescents.(25)

EPILEPTIC SEIZURES THAT HAVE CHARACTERISTICS OF PAROXYSMAL NONEPILEPTIC EVENTS:
Epileptic seizures often have features: syncope, psychogenic seizures, migraine, sleep disorders and lateralizsed vascular accident.

1. Frontal seizures from the supplemental motor areas often resemble sleep disorders,
2. Ictus emetikus and certain nonepileptic status in children are often misdiagnosed as nonepileptic event, as clinically, they mostly resemble migraine, conductive disorder or encephalitis.
3. Visual seizures are usually diagnosed as basilar migraine with visual aura, because their clinical pic-ture resembles it.
4. Simple focal seizures with epigastric aura are most often treated over years as recurrent abdominal pain, since they dominate the clinical picture,
5. Simple focal seizures with panic seizures im-press as behavioral disorders and are usually treated for years by a psychologist as behavioral disorders.

LABORATORY FINDINGS

There are no reliable laboratory markers for epileptic seizures. Measurement of postictal serum concentrations of prolactin, that remains elevated for 20 minutes after the epileptic seizure, is of very limited use. Prolactin is elevated in convulsive and complex focal seizures, but it can be elevated in convulsive syncope, psychogenic sei-zures and nipple stimulation. Serum prolactin falls after repeated seizures, which further compromises its impor-tance for the diagnosis of epilepsy. (26)

ALTERNATIVE DISEASES MOST COMONLY DIAGNOSED AS EPILEPSY ARE:
— Convulsions
— Febrile seizures
— Syncope
— Electrolyte disturbance
— Hypoglycemia
— Vitamin B 12 deficit— Aromatic amino acid decarboxylase deficit
— Mitochondrial diseases
— Encephalitis
— Meningo-encephalitis
— snoring
— Obstructive sleep apnea
— Syndrome of avoided sudden infant death
— Heart rhythm disorder
— Prolonged QT interval
— Pseudosiezures
— Panic seizure
— ADHD, attention deficit hyperactivity dis-order
— School failure
— Emotional problems
— Behavioral disorder
— Bipolar disorder
— Schizophrenia
— Stroke
— Transient ischemic seizure
— Migraine
— Basilar artery migraine
— Benign paroxysmal vertigo
— Kinetosis
— Recurrent abdominal pain
— Napping
— Drowsiness
— Excessive daytime sleepiness
— Falling asleep during laughter
— Night terrors
— Nightmares
— Somnambulism
— Neurocisticercosis
— Horea
— Fasciculations
— Myoclonus
— Tremor
— Tremulations
— Restless legs syndrome
— Brain injury
— Normotensive hydrocephalus
— Multiple Sclerosis

When diagnosing epilepsy in children it is nec-essary to consider all health conditions that impress as epilepsy and conditions that are relevant for the diagnosis of epilepsy.

PROCEDURE FOR DIAGNOSING EPILEP-SY IN CHILDREN may be laid out into five levels:

1. Differentiation of epileptic from nonepileptic seizures according to ictal phenomenology using descriptive ictal terminology.
2. Determination of seizure types according to the list of epileptic seizures, and defining brain localiza-tion and precipiatating stimulus in reflex seizures.
3. Setting syndromic diagnosis of epilepsy, accord-ing to the epileptic syndromes list and accepting the fact that syndromic diagnosis may not always be set.
4. Setting etiology diagnosis, according to the known classification of diseases that are associated with epileptic seizures or epileptic syndromes; defining genetic defect whenever possible and specific pathological substrate (neuroimsging) for symptomatic focal epilepsy
5. Definition of epilepsy according to the ICIDH-2 Classification of Diseases.

PREVENTING DIAGNOSTING MISTAKES IN CHILD EPILEPTOLOGY

Improvement of diagnostic procedures in children epileptology is imperative and it requires:
— Adequate training of medical practitioners and pediatricians who monitor the child, and ad-equate training of epilepsy specialist who should be the final link in diagnosing epilepsy in children and deciding on introducing continuous AET.
— Full cooperation of physicians with the child and parents/guardians and ability to gather all relevant information about the symptoms and signs of disease, as well as personal and family history of the child.
— Availability of laboratory, neurophysiology, neuroradiology and other technological procedures necessary for diagnosing epilepsy types and etiology.
— Full engagement of parents/guardians and the child (age permissible) in all diagnostic and thera-peutic procedures and decision-making.

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