CLINICAL AND PARACLINICAL CORRELATIONS IN WEST AND LENNOX-GASTAUT SYNDROMES

ABSTRACT:

The objective of the study. West syndrome (WS) and Lennox-Gastaut syndrome (LGS) are two of the 10 types of epileptic encephalopathies (EE) currently recognized. They are the most common forms of EE and have the best defined clinical and electroencephalographical features in this group. As literature has shown in the last five years, the evaluation by means of imagistic investigation methods ( CT, MRI, PET, SPECT, f-MRI) whether used independently or in combination with classical and modern EEG recordings , there is a statistically significant association between the main types of seizures and each form of EE and between each form of EE and the characteristics of the captured imagistic changes. Statistics show suggestive and representative associations . I noticed these facts by studying the above mentioned forms of investigation within a group of 20 patients ( 12 diagnosed with WS and 8 with LGS). Materials and methods. The study group consisted of 20 patients aged 2 months to 6 years. Based on inclusion criteria formulated for each entity they were diagnosed and included in the study group. Medical history was taken and the patients underwent general clinical examination, neuropsychiatric examination, repeated EEG recordings and CT examinations (CT), cranial nuclear magnetic resonance (MRI) (in one case angiographic MRI sequences were needed) and ultrasound examination (US). Frequency patterns were used to obtain numerical and percentage data. Averages and SD were calculated. Differences were considered to have statistical significance at a value of the parameter p less than 0.05.Results and conclusions. After both types of seizures identified and quantified from history taking as well as the obtained imagistic aspects were subjected to a thorough statistical analysis, a statistically significant coefficient p resulted, with values of 0.05 in the relationship between the mainly symptomatic forms of the studied entities and CT examination, some (a few) with localized value. Keywords: computed tomography, magnetic resonance image, epileptic encephalopathies, West syndrome, Lennox-Gastaut syndrome.

INTRODUCTION

The term of epileptic encephalopathy (EE) dates from 1976, when Ohtahara described the syndrome that bears his name considering it at that time as the earliest form of EE. According to a new concept, EE are defined as the abnormal epileptic conditions which are considered to contribute to progressive disorders of brain function. Other authors consider that childhood EE are resistant to treatment, they are characterized by multiple seizure types and a slow diffuse EEG with multifocal or generalized paroxystic anomalies. Unlike EE, epileptiform encephalopathy (EEp) refers to ab-normal epileptiform activity recorded by EEG without marked critical clinical activity. Epileptiform events (such as peaks, fast waves and sharp-wave discharges) present in this disorder indicate a state of cortical “ir-ritation” which does not mean that the patient has epilepsy. Nonconvulsive epileptic status, which often consists only of a light degree of impaired conscious-ness accompanied by an aspect of electrographic status epilepticus focal or generalized is considered by some authors (Riviello, 2002) a form of EE. Epileptic en-cephalopathy forms currently recognized as part of this group are: early myoclonic encephalopathy, Ohtahara syndrome, West syndrome, Dravet’s syndrome, myo-clonic status in nonprogressive encephalopathy, Len-nox-Gastaut syndrome, Landau-Kleffner syndrome, Doose syndrome, epilepsy with continuous slow -wave during slow wave sleep (other than Landau-Kleffner syndrome ) and gelastic epilepsy. West syndrome (WS) and Lennox-Gastaut syndrome (LGS) are the most common forms of EE and the clinical epileptic and electroencephalographic characteristics are best de-fined in this group. In West syndrome the main clinical epileptic picture is represented by the infantile spasms. They may be mainly in flexion, in extension and mixed, symmetric. In addition, due to modern techniques of evidence other types have been described, such as: asyn-chronous spasms (include a part of the body before an-other within the same spasm), focal spasms (very short muscle contractions, accompanied by lateral deviation of the eyes or side “jolt” of the head); spasms combined with partial seizures (three distinct cases were observed as follows: partial seizures followed in several seconds by spasms in bursts, alternation of partial seizures and spasms in bursts which started with partial seizures,partial seizures gradually replaced by epileptic spasms in bursts with the overlapping of the two), spasms preceded by partial seizures in epilepsy development, subtle spasms which occur as face muscles contractions the opening or closing of the eyes, eyeballs’ movements (up, down, convergent), raising of shoulders, grimacing, yawning, spasms preceded by short atonia, subclinical spasms whose presence can be seen on the EEG trails which show amplitude decrease and increased fre-quency followed by slow waves of high amplitude with fast rhythmic activity each lasting 1-2 sec., repeated at every 10 seconds; drop attacks seizures occurring in cases with late-onset . Lennox-Gastaut syndrome is characterized clinically in epilepsy by a polymorphism of the seizures. Tonic seizures may include: axial seizures, axial-rhizomelic seizures and global seizures. Atypical absences are accompanied by a light degree of impaired consciousness and can be accompanied by changes of the tonus and severe myoclonia. Atone seizures and drop attacks may involve all or only the extreme cephalic trunk. Myoclonic seizures (original-ly not included among the seizures that characterize LGS. Drop attacks (epileptic falls) are considered to be the result of a varied number of types of seizures (atonic, tonic, myoclonic-atonic and less frequent myo-clonic). Nonconvulsive status epilepticus (SE) include the following types: absence SE, tonic SE, myoclonic SE, mixed tonic SE and absence.

Materials and methods. The studied group included 20 patients aged 2 months to 6 years. Patients were hos-pitalized and investigated in the Pediatric Neuropsy-chiatry Clinic ofTargu Mures in the period 1999-2009. The patients benefited from regular admissions every 3 months, sometimes shorter periods oftime depending on the evolution of frequency and intensity of seizures The therapeutic formula was adjusted in accordance with the practical guidelines and individual patient’s needs. Based on inclusion criteria formulated separately for each they were diagnosed and included in the group.

INCLUSION CRITERIA FOR WEST SYNDROME

Types of seizures: spasms (s) in flexion and extension, combined s. (in flexion and extension), asym-metric s., asynchronic s., s. preceded by short atonia, s. preceded by partial seizures during epilepsy, focal s., subtle s., subclinical s;
The onset of seizures: between 3 and 7 months (before 1 year, rarely before 3 months);
EEG patterns: hipsarrythmia with its different variants (asymmetric, altered, atypical, fragmentary, unilateral);
Neurological syndrome: variable (spastic forms, hypotonic or diskinetic of tetra paresis, hemiparesis, paraparesis).

INCLUSION CRITERIA FOR LENNOX-GASTAUT SYNDROME

Seizure types: tonic seizures, atonic seizures, epileptic absences, myoclonic seizures, drop attacks, sta-tus epilepticus (sometimes persistence of infant s. or their early appearance)

Onset of seizures: after the age of 1 year (if moving from SW) and between 3 and 5 years in de novo forms;
EEG patterns: a) paroxysms of rapid rhythms or fast rhythms sharp-waves characteristic of tonic seizures, most frequently observed in slow wave sleep, b) generalized discharges of slow-wave complexes, bilateral, synchronous, symmetrical and of high amplitude on previous derivations , characterizing atypical absences c) inter-ictal multifocal spikes or slow slow-wave complexes, predominant in frontal and occipital areas; ) outbreaks of multiple independent spikes in the transition from the H pattern to the pattern of slow-wave complexes.
Neurological syndrome: variable (a significant proportion of hypotonic syndrome).

All patients underwent a thorough history, focused on obtaining accurate information and as many de-tails as possible regarding the development of various types of seizures. By this rigour we tried to compensate the limited available techniques in general, and in this respect in particular. The table below (Table 1) presents the types of seizures in the order they mani-fested in time. We considered important to note the age at which patients were studied. All patients re-ceived repeated EEG reco rds in dynamics. Record-ings (considering the age and low cognitive level of little patients) were performed in the drug-induced sleep with chloral-hydrate solution at a concentration of 10% administered intrarectaly. In situations where the desired effect was not obtained, before adminis-tration of chloral-hydrate, patients were deprived of sleep. All patients received three types of imagistic investigations: CT, MRI and ultrasonography (USG).Of the 20 patients, 18 had cranial CT examinations performed, 12 had cranial MRI (in one case angio-graphic sequences were needed) and 8 patients re-ceived both types of examination. To obtain relevant data, with a corresponding resolution of 1T devices, patients were sedated by the children intensive care services to avoid motion artifacts as much as possible.

RESULTS AND CONCLUSIONS

The obtained data (clinical and laboratory) were evaluated both separately and together and even before applying specific statistical tests , the above table (Table I) shows that only 4 of the 20 subjects inves-tigated and evaluated presented no changes (and of these only three were CT scanned and 1 underwent MRI and CT examinations ). Of the remaining 16, 7 had brain atrophy (moderate in 4 cases and massive in 3 cases, 3 of these cases have benefited from MRI which showed the same aspect). In 2 cases poren-cephalic cysts were found (in different regions and hemispheres). Intracerebral calcification was found in 3 cases by CT cranial examination (all these cases were diagnosed with Bourneville tuberous sclerosis).

Were highlighted, hypoplasia of the corpus callo-sum, cerebellar vermis hypoplasia, ventriculomegaly, cerebellar atrophy. Regarding types of seizures, clinical polymorphism is usually, but not all types of sei-zures situations flagship (infantile spasms in West syndrome, namely generalized seizures in Lennox-Gastaut syndrome) accounted for the largest share. Seizure types in Table I are presented in order of ap-pearance. Age of onset seizures as shown in the table in most cases confirm data from literature studied, but there are cases (in reference to West syndrome), which is early onset (before 3 months) or late (after 7 months ).

Statistical analysis was performed using the SPSS software version 19. and GRAPH PAD PRISMA. For univariate analysis of the data we used %2 test (di-chotomous variables). Multivariate regression was also used where confidence intervals strongly suggested the presence of risk factors for various combinations. Tables of frequency were used to obtain numeric and percentage data. Averages and SD were calculated. Differences were considered statistically significant with a value of the parameter p less than 0.05.

TABLE 1

RFMS – right focal motor seizures; LFMS- left motor focal seizures; GTCS – generalized tonic-clonic seizures; GTS- general-ized tonic seizures ASfht-amiotonic seizures with flexion of head on the trunk; ASft- amiotonic seizures with flexion of the trunk; SF – spasms in flexion; SE – spasms in extension; AFS – asym-metric spasms in flexion ; ASE-asymmetric spasms in extension, SMAS – suplimentary motor area seizures; CFMS – complex focal motor seizures; SE-status epilepticus; NNS neonatal seizures, MS – myoclonic seizures MARS – myoclonic axial-rhizomelic seizures; NCSE non-convulsive status epilepticus, MES – myoclonic erratic seizures; RFMSSG/LFMSSG – right focal motor seizures/left focal motor seizures secondarily generalized. VM – ventriculomegaly; hCC/aCC/ACC – hypoplasia / aplasia / agenesis of the corpus callosum; ICC / IVC / PVC – intracerebral / intraventricular / periventricular calcifications; hC/aC – hypoplasia / cerebellar aplasia, CA (F, P, T, O); cerebral atrophies (frontal, parietal, temporal, occipital); HD (F, P, T, O) – hypodensity (frontal, parietal, temporal, occipital); AVM arterio-venous malformation; CN / SCN / SEN – cortical / subcortical / subependimar nodules; MC microcephaly; CS-craniosynostosis ; HC / IHC / EHC – internal / external hydrocephaly, CeA – cerebellar atrophy, Por. cyporencephalic cyst, MCM – mega cisterna magna Hbs – hypotrofia of brainstem; DM – delayed myelination

After applying statistical tests a coefficient p resulted. It is significant for West syndrome (p = 0.05) and less significant (but with a high risk factor) for Lennox-Gastaut syndrome (with a “peak” significant-ly around the age of 3 months for SW), which can be an important predictor (Figure 1, Table II).

As expected, the prevalence found was generalized tonic-clonic seizures, generalized tonic and those of the amiotonic in LGS (Figures 2, 3 and 4, Tables 3, 4 and 5). Somewhat surprisingly, in West syndrome, have not prevailed spasms, generalized tonic-clonic seizures but those amiotonic (Figures 5 and 6, Tables 6 and 7). This could be explained by the phenomenon of epileptic encephalopathy continuum, therefore, were crossing the WS forms in LGS, strongly sug-gest by the EEG records demonstrated and the dy-namic process of transformation which surprised the hipsaritmic pattern at slow spike-wave complex pat-tern. Although no statistical evidence demonstrates a measured value of the locator certainly corrobo-rate the clinical laboratory data (imaging), imaging investigations contribution was an important one, as confirmed data from the literature studied, capturing a significant portion of brain atrophy, cerebellar hy-poplasia, ventriculomegaly, hypoplasia of the corpus callosum.

The accuracy of data by combining real-time EEG recordings with different types of imaging investigations such as functional magnetic resonance imaging, SPECT, PET (located in a real and rapid progress), not only bring additional data value locator certainly, but offers strong support building the necessary data epilepsy surgery, a method that we use especially in Lennox-Gastaut syndrome.

FIGURE 1 / TABLE 2

S. WEST –Seizures age of onset (months)

FIGURE 2 / TABLE 3

SL – G – Generalized tonic seizure

FIGURE 3 / TABLE 4

SL – G Amiotonic seizures

FIGURE 4 / TABLE 5

S.LENNOX-GASTAUT Generalized tonic-clonic seizures

FIGURE 5 / TABLE 6

S. WEST – Generalized tonic-clonic seizures

FIGURE6 / TABLE 7

S. WEST – Amiotonic seizures

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