Epileptic spasms in infants: can video-EEG reveal the disease's etiology? A retrospective study and literature review.

Objective: Epileptic spasms are a type of seizure defined as a sudden flexion or extension predominantly of axial and/or truncal limb muscles that occur with a noticeable periodicity. Routine electroencephalogram supports the diagnosis of epileptic spasms, which can occur due to different causes. The present study aimed to evaluate a possible association between the electro-clinical pattern and the underlying etiology of epileptic spasms in infants. Materials and methods: We retrospectively reviewed the clinical and video-EEG data on 104 patients (aged from 1 to 22 months), admitted to our tertiary hospital in Catania and the tertiary hospital in Buenos Aires, from January 2013 to December 2020, with a confirmed diagnosis of epileptic spasms. We divided the patient sample into structural, genetic, infectious, metabolic, immune, and unknown, based on etiology. Fleiss' kappa (К) was used to assess agreement among raters in the electroencephalographic interpretation of hypsarrhythmia. A multivariate and bivariate analysis was conducted to understand the role of the different video-EEG variables on the etiology of epileptic spasms. Furthermore, decision trees were constructed for the classification of variables. Results: The results showed a statistically significant correlation between epileptic spasms semiology and etiology: flexor spasms were associated with spasms due to genetic cause (87.5%; OR < 1); whereas mixed spasms were associated with spasms from a structural cause (40%; OR < 1). The results showed a relationship between ictal and interictal EEG and epileptic spasms etiology: 73% of patients with slow waves and sharp waves or slow waves on the ictal EEG, and asymmetric hypsarrhythmia or hemi hypsarrhythmia on the interictal EEG, had spasms with structural etiology, whereas 69% of patients with genetic etiology presented typical interictal hypsarrhythmia with high-amplitude polymorphic delta with multifocal spike or modified hypsarrhythmia on interictal EEG and slow waves on the ictal EEG. Conclusion: This study confirms that video-EEG is a key element for the diagnosis of epileptic spasms, also playing an important role in the clinical practice to determine the etiology.

Telemedicine for Individuals with epilepsy: Recommendations from the International League Against Epilepsy Telemedicine Task Force.

Worldwide, People with Epilepsy (PWE) are confronted with several barriers to face-to-face consultations. These obstacles hamper appropriate clinical follow-up and also increase the treatment gap for Epilepsy. Telemedicine holds the potential to enhance management as follow-up visits for PWE are focused on more on clinical history and counselling rather than physical examination. Besides consultation, telemedicine can also be used for remote EEG diagnostics and tele-neuropsychology assessments. In this article, the Telemedicine Task Force of the International League Against Epilepsy (ILAE) outlines recommendations regarding optimal practice in utilizing in the management of individuals with epilepsy. We formulated recommendations for minimum technical requirements, preparing for the first tele-consultation and the specificities for follow-up consultations. Special considerations are necessary for specific populations, including paediatric patients, patients who are not conversant with tele-medicine and those with intellectual disability. Telemedicine for individuals with epilepsy should be vigorously promoted with the aim of improving the quality of care and ultimately reduce the wide clinician access related treatment gap across several regions of the globe.

Clinical and molecular characterization of mitochondrial DNA disorders in a group of Argentinian pediatric patients.

OBJECTIVE: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases. METHODS: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. RESULTS: Patients were 18 females and 9 males, with ages at onset ranging from 1 week to 14 years (median = 4 years). The clinical phenotypes were: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 11), Leigh syndrome (n = 5), Kearns-Sayre syndrome (n = 3), Chronic Progressive External Ophthalmoplegia (n = 2), Leber hereditary optic neuropathy (n = 2), myoclonic epilepsy associated with ragged-red fibers (n = 1) and reversible infantile myopathy with cytochrome-C oxidase deficiency (n = 3). Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK. Other point variants were found in complex I subunits, like MT-ND6, MT-ND4, MT-ND5; or in MT-ATP6. The m.13513G > A variant in MT-ND5 and the m.9185 T > C variant in MT-ATP6 were apparently de novo. The rest of the patients presented large scale-rearrangements, either the "common" deletion or a larger deletion. CONCLUSIONS: This study highlights the clinical and genetic heterogeneity of pediatric mtDNA disorders. All the cases presented with classical phenotypes, being MELAS the most frequent. Applying classical molecular methods, it was possible to achieve a genetic diagnosis in 30% of the cases, suggesting that this is an effective first approach, especially for those centers from low-middle income countries, leaving NGS studies for those patients with inconclusive results.

A Prospective Study on Changes in Nutritional Status and Growth Following Two Years of Ketogenic Diet (KD) Therapy in Children with Refractory Epilepsy.

INTRODUCTION: Epilepsy is a neurological disorder characterized by an increased susceptibility to seizures. The ketogenic diet (KD) is currently the most important alternative non-pharmacological treatment. Despite its long history of clinical use, it is not clear how this diet affects longitudinal growth in children. METHODS: A prospective study was designed to evaluate growth and nutritional status in 45 children on KD. Growth was assessed by measuring weight, height, and body mass index (BMI). Standard deviation scores (SDS) were calculated for all measurement parameters at KD initiation and at a two-year follow-up. RESULTS: Overall, 45 patients who completed 24 months on KD were enrolled. Median age was 6.6 years (0.8 to 17.3), with a male predominance (n = 23); 74% of the 45 patients were responders on seizure reduction at three months; 26% of patients were non-responders. In our study, using -1 SDS as a cut-off point, growth deceleration was observed in 9% (n: 4) of the patients; however, the nutritional status was maintained or even improved. No correlation with age, sex, or ambulatory status was found. CONCLUSIONS: The nutritional follow-up of these patients was helpful to improve overweight and thinness but could not avoid growth deceleration in some of them. These findings confirm that children with refractory epilepsy on KD treatment require careful growth monitoring.

Ictal blinking, an under-recognized phenomenon: our experience and literature review.

Ictal blinking (IB) is a very rare disease manifesting as an epileptic motor event in children and adults. Until now it has not been included in any classification of focal seizures of the International League Against Epilepsy Commission. It could be unilateral or bilateral, isolated or in association with other motor manifestations such as limbs' clonus and spasms. Its pathogenesis has not been clearly established: paroxysmal discharges from different areas of the brain could cause IB by activation of trigeminal fibers. Herein authors report three infants and a child with IB, observed in three pediatric centers in two different countries. We also performed a review of literature data, suggesting IB as a seizure type to be included in international classifications, and describing the specific electroencephalographic pattern of this condition.

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

AIM: We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. METHODS: Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. RESULTS: One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. CONCLUSION: The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Ketogenic diet in patients with epileptic encephalopathy with electrical status epilepticus during slow sleep.

UNLABELLED: Epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. PURPOSE: In this retrospective study we assess the efficacy and tolerability of the KD in patients with ESES syndrome. METHODS: Between March 1, 1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome were seen at our department. Twelve of them were placed on the KD and followed for a minimum of 18 months. RESULTS: The children had previously received a mean of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started. Eighteen months after initiating the diet, seven of the initial patients (58%) remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and the remaining three children (24.9%) had a <50% decrease in seizures. In the patient who had become seizure free and in the one who had a 75-99% seizure decrease AEDs were reduced. CONCLUSION: The KD is a well-tolerated treatment option for patients with ESES syndrome, not only for structural cases but also for those with an unknown etiology. The diet should be considered in the management of this syndrome.

Panayiotopoulos syndrome and diffuse paroxysms as the first EEG manifestation at clinical onset: a study of nine patients.

To present a retrospective study of nine children with Panayiotopoulos syndrome associated with diffuse spikes and waves as the sole EEG manifestation at onset. Charts of children with typical clinical criteria of Panayiotopoulos syndrome, electroclinically followed between February 2000 and February 2012, were reviewed. Among 150 patients who met the electroclinical criteria of Panayiotopoulos syndrome, we identified nine children who presented with the typical clinical manifestations but who, on EEG, only had diffuse paroxysms at onset that continued along the course of the syndrome. In three, in addition to the diffuse paroxysms, focal spikes appeared later. From a clinical point of view, other features were otherwise unremarkable. Diffuse spike-and-wave discharges were observed in all patients when awake and during sleep (100%). Later, three children also had focal spikes during sleep, which were occipital in one, frontal in one, and temporo-occipital in the remaining patient. Spikes were activated by sleep in all three cases. During disease evolution, no particular electroclinical pattern was observed. Two patients who received clobazam and carbamazepine, respectively, did not respond well to the drugs and valproic acid was added with excellent seizure control. Outcome was good. We present evidence that patients with Panayiotopoulos syndrome may have diffuse discharges at onset as the sole EEG manifestation, which last throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of Panayiotopoulos syndrome.

Encephalopathy with status epilepticus during sleep: unusual EEG patterns.

PURPOSE: To retrospectively analyze the electroclinical characteristics, etiology, treatment, and prognosis of patients with epileptic encephalopathy with status epilepticus during sleep (ESES) with unusual EEG features and to corroborate if this series of patients is part of the ESES syndrome. METHOD: Charts of 17 patients with typical clinical manifestations of the ESES syndrome with focal ESES of non-REM sleep at onset and during the focal ESES phase, or bilateral synchronic and asynchronic ESES with a symmetric or asymmetric morphology, continuous or subcontinuous and sometimes multifocal paroxysms with or without slow-wave activity during slow sleep seen between 2000 and 2012 were analyzed. RESULTS: Mean patient follow-up from onset was 7.5 years. An idiopathic cause was found in seven patients, a structural cause in eight, and etiology was unknown in the remaining two. The median age at onset of the unusual ESES syndrome was 7 years. During the ESES phase, 15 children developed new seizure types, negative myoclonus was observed in seven patients, positive myoclonus in five, and absences in nine. Six patients had motor impairment, two had auditory verbal agnosia, and two had motor speech impairment. Attention deficit hyperactivity disorder was observed in four, aggressiveness in six, memory deficit in two, and impaired temporospatial orientation in four. The patients with focal ESES in the frontal region showed behavioral disturbances and/or motor deterioration, and in those with temporo-occipital involvement the dominant clinical manifestations were language and/or behavioral disturbances. CONCLUSION: Our patients with typical clinical manifestations of ESES syndrome but with unusual EEG patterns may be variants of this syndrome.

Ketogenic diet in pediatric patients with refractory focal status epilepticus.

UNLABELLED: The ketogenic diet (KD) has been used as an alternative treatment for patients with refractory status epilepticus (SE). PURPOSE: In this retrospective study we assess the efficacy and tolerability of the KD in patients with refractory SE. METHODS: Between March 1, 2010 and January 1, 2014, 10 patients who met the diagnostic criteria of refractory SE seen at our department were placed on the KD and followed for a minimum of 6 months. RESULTS: Ketonuria was reached within 2-4 days (mean 3 days) for all patients. Seizures stopped in two patients and five patients had a 50-75% seizure reduction within 2-5 days (mean 2.5 days) following the onset of ketonuria and within 5-7 days (mean 5 days) following the onset of the diet. Three patients had a <50% seizure reduction and all of them had severe adverse events so the diet was discontinued. Seven patients remained on the diet for 6 months to 3 years (mean 1.5 years). In all seven patients within 4 months the seizures recurred, but their quality of life did not worsen. The frequency of the seizures consisted of weekly seizures in two, monthly seizures in two, occasional seizures in two, and isolated seizures in one. All of them kept a good tolerability of the diet. CONCLUSION: The KD is an effective and well-tolerated treatment option for patients with refractory SE. In patients with focal SE secondary to inflammatory or probably inflammatory diseases, the KD should be considered earlier in the course of the treatment.

Ketogenic diet in patients with Lennox-Gastaut syndrome.

PURPOSE: The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epilepsy. Lennox-Gastaut syndrome (LGS) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. In this prospective study we assess the efficacy and tolerability of the KD in patients with LGS. METHODS: Between March 1, 1990 and April 1, 2013, 61 patients who met diagnostic criteria of LGS were seen at our department. Twenty of them were placed on the KD and followed for a minimum of 16 months. RESULTS: The children had previously received a mean of 6.5 different AEDs and were on a mean of 2.5 AEDs when the diet was started. Eighteen months after initiating the diet, fifteen of the initial patients (75%) remained on the diet; three patients (15%) were seizure free, three (15%) had a 75-99% decrease in seizures, two (10%) had a 50-74% decrease in seizures, and the remaining seven children (35%) had a <50% decrease in seizures. Three seizure-free patients were tapered off the diet after remaining seizure free. In the three patients who had a 75-99% decrease in seizures AEDs were reduced. CONCLUSION: The KD is an effective and well-tolerated treatment option for patients with LGS, not only for those with cryptogenic, but also for those with structural LGS. The diet should be considered early in the course of this syndrome.

Landau-Kleffner syndrome: a study of 29 patients.

PURPOSE: The aim of the study was to retrospectively analyze the electroclinical features, etiology, treatment, and prognosis of 29 patients with Landau-Kleffner syndrome (LKS) with a long-term follow-up. METHODS: Inclusion criteria were a diagnosis of LKS with: (1) acquired aphasia or verbal auditory aphasia; (2) with or without focal seizures, secondarily generalized tonic-clonic seizures, absences, or atonic seizures. RESULTS: Mean follow-up was 12 years. All cases except six had seizures. Before the onset of aphasia, developmental language and behavioral disturbances were present in 19 and 14 patients, respectively. All patients had verbal auditory agnosia. Aphasia was severe in 24 patients and moderate in five. Nonlinguistic cognitive dysfunctions were moderate in 14 patients. Behavioral disturbances were found in 16 patients. During the continuous spike-and-wave discharges during slow sleep phase, the spike-wave index was >85% in 15, 50-85% in eight, and 30-50% in four. In two patients, the EEG recording showed occasional bilateral spikes, without continuous spike-and-wave discharges during slow sleep. In this phase, the awake EEG recording showed more frequent interictal abnormalities, predominantly in the temporal regions. Eight patients recovered language completely, but the remaining patients continue to have language deficits of different degrees. CONCLUSION: Landau-Kleffner syndrome is an epileptic encephalopathy characterized by acquired verbal auditory aphasia and seizures in most of the patients associated with continuous or almost continuous spike-and-wave discharges during slow wave sleep. The most commonly used treatments were clobazam, ethosuximide, sulthiame. High-dose steroids were also administered. Adequate and early management may avoid language and cognitive deterioration.

Congenital hemiparesis, unilateral polymicrogyria and epilepsy with or without status epilepticus during sleep: a study of 66 patients with long-term follow-up.

AIM: We retrospectively analysed the electroclinical features, treatment, and outcome in patients with unilateral polymicrogyria (PMG), focussing on epileptic syndrome with or without encephalopathy, with status epilepticus during sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) syndrome. METHODS: From June 1990 to December 2012, 39 males and 27 females, aged 5-26 years, were studied. We did not include patients with bilateral PMG or cases with unilateral PMG associated with other cerebral lesions. The mean follow-up period was 12 years (range: 3-22 years). RESULTS: Mean age at epilepsy onset was 6.5 years. Focal motor seizures occurred in all cases and 25 had secondary generalised seizures. Six patients also had complex focal seizures. Interictal EEG recordings showed focal spikes in all cases. For 43 of 53 patients with epilepsy, aged 2-9.5 years, the electroclinical features changed. An increase in frequency of focal motor seizures was reported in 20 patients, negative myoclonus occurred in 32 patients, atypical absences in 25 patients, and positive myoclonus in 19 patients. All patients had a continuous symmetric or asymmetric pattern of spike-wave activity during slow-wave sleep. CONCLUSION: For patients presenting with congenital hemiparesis, negative or positive myoclonus, and absences and focal motor seizures with ESES/CSWS, unilateral PMG should be considered. Brain MRI is mandatory to confirm this cortical malformation. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. For refractory cases, high-dose steroids were administered and surgery was performed in two patients. Outcome was relatively benign.

Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Encephalopathy with hemi-status epilepticus during sleep or hemi-continuous spikes and waves during slow sleep syndrome: a study of 21 patients.

PURPOSE: To retrospectively analyze the electroclinical features, etiology, treatment, and prognosis of 21 patients with encephalopathy with hemi-status epilepticus during sleep (ESES) or hemi-continuous spikes and waves during slow sleep (CSWSS) syndrome. METHODS: Charts of 21 patients with hemi-ESES/CSWSS syndrome followed between 1997 and 2012 were analyzed. Inclusion criteria were: (1) Focal seizures or apparently generalized seizures and focal EEG epileptiform discharges; (2) Further occurrence of atypical absences, and myoclonic, atonic, and/or generalized seizures; (3) Cognitive impairment and/or behavioral disturbances; (4) Hemi-continuous spike-and-wave discharges during slow sleep in more than 85% of non-REM sleep at onset and throughout the ESES/CSWSS period. RESULTS: Mean follow-up from onset of hemi-ESES/CSWSS was 8 years (range, 2-15 years). Idiopathic cases were not identified. Unilateral polymicrogyria was found in 11, shunted hydrocephalus in four, a porencephalic cyst associated with polymicrogyria in three, and a thalamic lesion in three children. All started with focal seizures with or without secondary generalization. During the hemi-ESES/CSWSS period, all children developed new types of seizure, such as negative and positive myoclonus, absences, motor deterioration, cognitive impairment, and behavioral disturbances. All AED responders returned to baseline cognitive development. Seven patients were refractory to AEDs. CONCLUSION: Our study suggests that the hemi-ESES/CSWSS syndrome has electroclinical features compatible with an epileptic encephalopathy. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. In refractory cases, high-dose corticosteroids were administered. Although the number of patients in this study is too low to draw definite conclusions, we consider that in children with hemi-ESES/CSWSS secondary to a unilateral lesion, surgery should be considered.

Encephalopathy with status epilepticus during sleep or continuous spikes and waves during slow sleep syndrome: a multicenter, long-term follow-up study of 117 patients.

PURPOSE: To retrospectively analyze the electroclinical features, etiology, treatment and prognosis of 117 patients with encephalopathy with status epilepticus during sleep (ESES) or continuous spike and waves slow sleep (CSWSS) syndrome with a long-term follow-up. METHODS: Charts of 117 patients with ESES/CSWSS syndrome followed between 1990 and 2012 were analyzed. Inclusion criteria were: (1) focal seizures or apparently generalized seizures and focal EEG epileptiform discharges; (2) further occurrence of atypical absences, and myoclonic, atonic, and/or generalized seizures; (3) cognitive impairment and/or behavior disturbances; (4) continuous spike-and-wave discharges during slow sleep in more than 85% of non-REM sleep. Patients with spike-and-wave discharges in less than 85% of slow sleep were also analyzed. KEY FINDINGS: 'Mean follow-up from onset of ESES/CSWSS was 13 years (range, 2-22 years) in the symptomatic/structural and non-idiopathic group consisting of 79 children and 10.5 years (range, 2-21 years) in the idiopathic group consisting of 38 children. The comparison of clinical findings and localization of paroxysmal EEG abnormalities (focal, multifocal, or generalized) at the different stages (before, during, and after ESES/CSWSS) and the percentage of spike-wave index during ESES/CSWSS between the symptomatic/structural and non-idiopathic and the idiopathic group was not statistically significant. SIGNIFICANCE: ESES/CSWSS syndrome is an epileptic encephalopathy with similar electroclinical findings in children with a >85% spike-wave index and those with a <85% spike-wave index. In this series of patients, the most commonly used treatments were clobazam, ethosuximide, sulthiame, alone or in combination. In refractory cases, high-dose steroids were administered. Among the AED responders, the idiopathic cases returned to normality and the structural cases returned to baseline cognitive development.

Electroclinical overlap of two types of epileptic encephalopathy occurring in the same children in a certain age period?

In this study, we describe three patients who each had an electroclinical overlap of two different epileptic encephalopathies (EE), with onset in a certain age period. Patient 1 had electroclinical features compatible with continuous spikes and waves during slow sleep (CSWSS) syndrome that changed into Lennox-Gastaut syndrome (LGS) (symptomatic, cause porencephalic cyst) at the age of 8.5 years. Patient 2 had LGS which evolved into CSWSS at the age of 6 years (symptomatic, cause polymicrogyria). The third patient had cryptogenic CSWSS syndrome at age the age of 7 years which evolved into LGS at the age of 7.5 years. All three patients could be considered to have two EE: CSWSS syndrome and LGS or to have had overlapping features of these epileptic syndromes.

Benign infantile seizures and paroxysmal dyskinesia: a well-defined familial syndrome.

UNLABELLED: The aim of this study was to analyze the electroclinical features and evolution in patients with benign infantile seizures (BIS) associated with paroxysmal dyskinesia (PD). PATIENTS AND METHODS: Among 198 patients with BIS (78 of whom were familial cases), we evaluated 12 unrelated patients with BIS and PD seen at two pediatric neurology departments from January 1990 to February 2009. RESULTS: The patients were eight boys and four girls, one of whom was not a familial case. The time of follow-up was between 6 and 19 years. Median age at onset of epilepsy was 7 months (R: 5-18 m). Seizures were brief, focal, with or without secondary generalization, and occurred in clusters in 58% of the cases. Seven of 12 patients with BIS and 13 family members had PD. The age at onset of PD was between 5 and 18 years and it was characterized by choreoathetosis in 12 and dystonia in 8. PD was kinesigenic in all cases. As to family history, BIS was found in mothers in two patients, in fathers in five, in a grandfather in one, in grand-uncle in one, in uncles in four, in brothers in three, and in sisters in three other patients. PD was found in fathers in four patients, in the mother in one, in a brother in one, in a cousin in three, in an uncle in one, in an aunt in one, and in grandfathers in two. During follow-up, one patient and a relative with BIS from two different families presented Rolandic epilepsy. The father of the case with BIS and Rolandic epilepsy also had BIS and benign focal seizures of adolescence. CONCLUSIONS: BIS and PD syndrome is a well-defined familial syndrome. BIS had the similar features described in patients with familial and non-familial BIS. The patient with non-familial BIS who developed PD later, suggests that non-familial forms may have a genetic cause and may be caused by de novo mutations.