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[Channelopathies in neurology].

INTRODUCTION: The main function of ionic channels are the conduction, recognition and selection of specific ions. They open and close in respond answer to electrical, mechanical and chemical stimulus, acting in the excitation or transmission of diverse tissues. DEVELOPMENT: The clinical and molecular manifestations of channelophathies are varied and use to shown up in continuous or paroxystic ways. Alteration of Ca channels cause muscle dysfunction periodic paralysis with or without potassium changes, myasthenia or myasthenic disorders, like Lambert Eaton syndrome, amyotrophic lateral sclerosis, Central Core disease, malignant hyperthermia. Cl and Na channels alterations produce myotonic diseases: Thomsen, Becker and paramyothonies, potassium sensible paralysis, fluctuant congenital myotonic, Andersen s syndrome. Channelopathies also produce various episodic ataxia type 1, type 2, spinocerebellar 6 and familial hemiplegic migraine. Abnormal paroxystic movements are present as channelophaties: episodic nocturnal dystonia, paroxystic dyskinesia. In some families are associates abnormal episodic movements and epilepsy. Several epileptic syndromes are also related with channels dysfunction: frontal lobe nocturnal epilepsy, choreoatetosis epilepsy, benign neonatal convulsions, generalized epilepsy with febrile convulsions plus. CONCLUSIONS: Voltage gated channels dysfunction are related to diseases with episodic phenomena or permanent conditions on muscle or neuronal tissues, with clinical and genetic heterogenous manifestations.

Humans↗
PubMed2002

[Pregnancy in WAG/Rij rats--changes in the levels of progesterone, estradiol and generalized absence epilepsy].

Progesterone and oestradiol serum level was investigated in WAG/Rij rats with genetically determined absences. Blood samples were drawn before and after the pregnancy following the parturition. The serum concentration of progesterone increased after the 3rd day of pregnancy. There is no increasing of oestradiol during pregnancy as large as this. The progesterone is kept high to the 18th day of pregnancy and drastically decreased before the parturition. Common duration of absences--spontaneous spikewave discharges (SWD), frequency and the duration of every SWD decreased from 3rd to 19th days of pregnancy before the parturition. On the basis of these data and modern investigations, regulation of GABAA receptor expression during pregnancy by progesterone (Brusaartd A. B. et al., 1999) it can be assumed that the changes in the parameters of SWD are possibly correlated with the progesterone changes in serum during pregnancy in WAG/Rij rats.

Animals↗
PubMed1998

[Comparison of the multifactorial model as a hereditary mechanism of non-myoclonic generalized idiopathic epilepsy and partial idiopathic epilepsy].

OBJECTIVE AND METHODS: An experimental study about the predictions from the multifactorial threshold model created by Falconer is presented, assuming that this model may explain the genetic mechanisms underlying the family aggregation of idiopathic epilepsies. RESULTS: We failed to confirm the following predictions from the falconer model: decreased prevalence of disease in relatives, proportional to decreased family links, and the order of birth effect. An heredity greater than 100% was calculated which is concordant with the presence of at least a locus with a major gen affect. CONCLUSION: Our results reject the multifactorial threshold effect and suggest the presence of a major gen or Mendelian effect. An analysis of complex segregation is suggested for future studies.

Adolescent↗
PubMed2002

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience.

PURPOSE: This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. METHODS: We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. RESULTS: Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. CONCLUSION: This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.

Adolescent↗
PubMed1985

Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy).

Juvenile myoclonic epilepsy (JME) is a special syndrome within the primary generalized epilepsies which is characterized clinically by irregular jerks of shoulders and arms (so-called impulsive petit mal) after awakening and electroencephalographically by bilateral-synchronous 4-6/s spike-wave complexes, often in the form of multispike-waves. The age of onset for this syndrome which occurs in 4-6% of all epilepsies is predominantly between 12 and 18 years. It mostly starts with isolated jerks which as a rule are soon followed by generalized tonic-clonic seizures (TCS). Jerks and TCS are provoked by sleep deprivation and predominantly occur after awakening (awakening epilepsy). Sleep deprivation and photostimulation are also very efficient in provoking specific EEG patterns. Exogenous factors have no etiological significance. Genetic studies suggest a polygenetic mode of inheritance and a lower threshold of manifestation in women. JME can be controlled very well by valproate and/or primidone. A complete cure, nevertheless, does not seem to be possible. Within the group of primary generalized epilepsies beginning in adolescence JME is closely related nosologically to the syndrome of juvenile absences and the syndrome of pure grand mal on awakening.

Adolescent↗
PubMed1987

Clorazepate therapy for intractable epilepsy.

Thirty-one epileptic patients with seizures refractory to conventional anticonvulsants were treated by adding clorazepate dipotassium to their regimen. Twelve cases showed improvement in seizure frequency, three of whom attained a seizure free state. Response to clorazepate was not related to the type of epilepsy, but patients with secondary generalized epilepsy tended to be less responsive than those with partial epilepsy. Among the various seizure types, generalized tonic-clonic seizures and simple partial seizures showed, although not significant, a tendency to be more responsive to clorazepate therapy than other seizure types, including complex partial seizures, atypical absence, atonic seizures, and tonic seizures. Drowsiness was the main adverse effect, of which 14 patients complained. Six patients were withdrawn from clorazepate because of drowsiness, but in the remaining 8 patients, this side effect disappeared within a week. The appearance of adverse effect was not related to the dose of clorazepate given. Clorazepate may be an effective secondary anticonvulsant in the treatment of intractable epilepsy.

Adolescent↗
PubMed1996

The I.L.A.E. classification of the epilepsies applied retrospectively to 1902 patients.

The I.L.A.E. classification of the epilepsies and epileptic syndromes was applied retrospectively to the epileptic seizure disorders of 1902 consecutive patients collected from a neurological consultant practice over a 30 year period. There were 265 patients with only a solitary seizure when they presented. These 265 included fewer instances of generalized epilepsies (14.0% versus 28.5%) and more instances of epilepsies of undetermined type (35.1% versus 20.4%) than the remaining 1637 patients. It was possible to categorize the epilepsy or epileptic syndrome present in 77.6% of all cases. The remainder could not be classified on the evidence available and thus fell into the I.L.A.E. classification's category of "epilepsies and syndromes undetermined whether focal or generalized'. The number of cases of such epilepsy of undetermined type decreased with increasing number of occasions on which patients were seen. Allowing for the effects of factors such as different age distributions in the various published series (in most series generalized epilepsies were more common in children), the distribution of epilepsies and epileptic syndromes diagnosed retrospectively in the present series was quite consonant with the data reported in the literature from contemporaneous series. In the various published series there were notable differences in the proportions of subjects allocated to the category of 'epilepsies and syndromes undetermined whether focal or generalized'. This raises the possibility that the categorizers' degrees of diagnostic confidence may have had appreciable effects on the reported distributions of epileptic syndromes in the different series. Some consensus regarding the degree of diagnostic probability acceptable for assigning a patient to a particular epileptic syndrome might yield more uniform outcomes from future epilepsy classificational attempts.

Adolescent↗
PubMed2005

Effect of epilepsy on psychomotor function in children with uncomplicated epilepsy.

This study assessed the impact of epilepsy on motor function in children. We aimed to analyze the effect in uncomplicated epilepsies (cryptogenic partial and idiopathic generalized epilepsy). A group of 87 children with epilepsy (47 males, 40 females; mean age 8y, standard deviation [SD] ly 9mo, range 4y 11mo to 12y 11mo), but without learning disability* or other neurological comorbid disorders, was compared with a control group of 107 children (76 males, 31 females; mean age 8y 4mo, SD 2y 2mo, range 4y 7mo to 12y 2mo). The differences in main motor skills and psychomotor speed were analyzed using the Movement ABC and computerized measures for simple reaction times and finger tapping. No significant difference in motor function was found. The overall psychomotor development of children with epilepsy is comparable to controls. However, a significant slowing of psychomotor speed in the group with epilepsy was reported. No relation with antiepileptic drug treatment was demonstrated and no difference in psychomotor speed between different types of epilepsy was found. The existence of a condition leading to excessive neuronal discharge leads to a general cortical inhibition. The slowing of psychomotor speed in children with uncomplicated epilepsy may be the behavioural presentation of this inhibition.

Child↗
PubMed2001

Magnetoencephalography in the detection of focal lesions in West syndrome.

BACKGROUND: According to the international classification of epilepsy syndromes, West syndrome (WS) is a form of generalized epilepsy. However, it is known that localized lesions can induce WS and that patients with WS often subsequently develop focal seizures. We evaluated such patients using magnetoencephalography (MEG). METHOD: Fourteen patients of 3 months to 6 years of age who had or who had previously had WS were examined. MEGs were recorded using a laying-type whole-cortex MEG system with a 160-channel first-order gradiometer. Twelve-channel electroencephalography (EEG) and one-channel electrocardiography (ECG) were simultaneously recorded. Equivalent current dipoles were estimated at the point of spikes on the EEG. RESULTS: Patients were classified by magnetic resonance imaging (MRI) findings into a focal lesion group (group F, n=7) and a non-focal lesion group (group N, n=7). The dipoles estimated from the MEG were classified into three groups: W, with the dipoles distributed over a wide brain area (n=7); WC, dipoles distributed over a wide area along with a dense dipole distribution in a specific cortical area (n=3); and C, closed dipole distribution in a unilateral cerebral focal area (n=4). Patients were also classified by the stage of the disease during which the MEG was recorded, and by the type of seizure they experienced. Those with hypsarrhythmia examined early in the disease all had pattern W regardless of their lesion group, whereas those examined later exhibited more diverse dipole patterns that corresponded to seizure type. CONCLUSIONS: Dipoles were distributed widely over bilateral cerebral cortex when patients had infantile spasms with hypsarrhythmia whether or not they had focal lesions. The dipole distribution pattern in MEG changed according to changes in seizure type.

Child↗
PubMed1993

Drop attacks and epileptic syndromes.

1. In addition to 4 types of drop attacks previously described by Ikeno et al., we could ascertain the falls of the myoclonic-tonic type in genuine drop attacks. The genuine drop attacks were seen in Lennox-Gastaut syndrome, epilepsy with myoclonic-astatic seizures and other symptomatic generalized epilepsies, and never in partial epilepsies. 2. None of the patients with partial epilepsy revealed genuine drop attacks as defined. Their drop attacks were slower (i.e. the falls were completed in more than 1 sec.). 3. In the 15 patients with Lennox-Gastaut syndrome, the drop attacks disappeared in 8 patients, and decreased in severity and frequency in 3 patients. Namely, the intractability of drop attacks in two-thirds of the children decreased as the patients grew older. This finding must be taken into consideration when patients with drop attacks are considered for surgical treatment of their epilepsy.

Adolescent↗