Ref.:21.206
MINISTRY OF HEALTH DEPARTMENT OF PUBLIC AND HEALTH SERVICES HOSPITAL ARCBISHOP MAKARIOS III PAEDIATRIC CLINIC NICOSIA-CYPRUS
MARCH 2005
URGENT Name: Maria-Fotini Kallimachou D.O.B.: 25/04/02 U.N.: 121617 NICOSIA - CYPRUS Diagnosis: Severe Myoclonic Epilepsy of Infancy (SMEI) Dravet Syndrome Maria-Fotini a 21/2 years old child is the first and the only child of her parents who are phenotypically healthy and non-consanguinoeus. They are both teachers. Maria-Fotini was deliveredat term (/39/40 weeks of gestation) following her mother’s first uncomplicated pregnancy by emergency caesarean section because of fetal distress. The on set of the labour was spontaneous. Her birth weight was 2900 grms and no resuscitation was required. She was a breast fed baby who has been very healthy making excellent developmental progress. Since the age of three months she has been developing paroxysmal events of various types and duration. The seizures most of the time have focal onset and they become secondarily generalized. They are both febrile and afebrile. However high temperature and hot water during the bath have been proved to be precipitating factors. The parents have made a very informative and detailing diary of the seizures. She presents eyelids myoclonias, jerking of the limbs, generalized tonic clonic movements, and loss of muscle tone – hypotonia with staring. They are occasionally associated by perioral cyanosis and mostly by loss of consciousness. Duration varies from a few seconds up to a few minutes (15-20). She required hospitalization twice for convulsive status epilepticus. She has been also hospitalized on several other occasions in view of repeated seizures on the same day. They occur frequently. She never remained seizures free actually. There was a period of six months during which she developed only febrile events but frequent ones. 1
Maria-Fotini’s seizures deteriorated when we tried Carbamazepine/ Oxcarbamazebine and Lamotrigine. A trial with Pyridoxine was not beneficial either. She is now on treatment with: Valproic Acid (Depakine): 250 mg morning 250 mg night Epitomax (Topamax): 50 mg morning 50 mg night On clinical examination she is a lovely sociable little girl who looks happy. There are no dysmorphic facial features. No birthmarks of any neurocutaneus disorder are found. HC=48,5 cm > 25th centile BW = 13 kg = 25th centile Muscle tone and Muscle power are normal. Deep tendon reflexes are elicited normal and symmetrical on both upper and lower extremities. During her first year of her life developmental progress seemed to be within normal ranges apart from slight delay of gross motor milestones. Mentally she was according to her age, and she has been always alert. However during second year of life global developmental delay was undoubtedly obvious. Maria-Fotini was able to walk independently showing ataxic gait at the age of two years. She is still ataxic. Her fine motor abilities and coordination are impaired too. She is hyperactive with profound attention deficit. She has speech delay development both expressive and receptive language (expressive much more delayed than receptive). They are bilingual at home as her nanny comes from Russia. She can point pictures. She recognizes and shows body parts on request. She understands verbal commands. She can imitate voices of familiar animals. She says only a few words, no phrases, in Greek and in Russian. Laboratory examinations The following tests were carried out and the results were within normal ranges: FBC and Routine biochemistry screening Plasma Lactate CSF Lactate Serum Ammonia levels Plasma Aminoacids Urine Organic Acids CSF viral studies (PCR) (-) and Serology virology (-) 2
EEG performed at the age of five months at Great Ormond Hospital for Sick Children in London was normal. EEG repeated at the age of one year was normal as well. MRI brain at the age of five months was without any abnormalities. MRI brain at the age of one year (08/05/2003): There is evidence of minimal periventricular hyperintensities mainly involving the parietal lobes. In addition there is minimal prominence of the ventricles and extraaxial CSF spaces. No restricted diffusion areas are seen. In conclusion these findings are compatible with parietal minimal ischemic changes. In addition she has developmental delay.
Latest Invastigations I suggested that Maria-Fotini should go to France at a specialized Epilepsy center. Therefore, a Video EEG was performed on the 19/01/05 at Hospital Robert Debre in Paris in the Paediatric Neurology Department under the care of Dr. Alexis Arzimanoglou and was again without any abnormalities. Additionally, genetic studies were carried out for Dravet Syndrom. The results will be ready at the end of March. Dr. Arzimanoglou said that: According to her seizures diary Maria-Fotini seems to have the Dravet Syndrome. On the other hand, she is not mentally delayed. In either case, her future development is expected to me rather bad. On the 26th of February 2005 Maria-Fotini had a status epilepticus (the third one) and required hospitalization for one day. Since then, she has been developing small absences and myoclonic seizures every day, of small duration (only a few seconds). These are counted from 15 –50 per day. OPINION: Maria-Fotini suffers from frequent, resistant seizures (myoclonic, focal and generalized). In addition she has developmental delay. It is obvious that the last two months Maria-Fotini’s seizures are more frequent. CONCLUSION: Since there isn’t any solution to Maria-Fotini’s health problem in Europe I recommend that the child must be transferred to the U.S. for further investigation and treatment. Mayo Clinic is the best appropriate hospital for her situation. I also suggest Cyprus Government cover all the medical expenses. Goula Stylianidou Child Neurologist HOSPITAL ARCBISHOP MAKARIOS III PAEDIATRIC CLINIC NICOSIA-CYPRUS 3
Ref.:21.206
MINISTRY OF HEALTH DEPARTMENT OF PUBLIC AND HEALTH SERVICES HOSPITAL ARCBISHOP MAKARIOS III PAEDIATRIC CLINIC NICOSIA-CYPRUS
MARCH 2005
URGENT Name: Maria-Fotini Kallimachou D.O.B.: 25/04/02 U.N.: 121617 NICOSIA - CYPRUS Diagnosis: Severe Myoclonic Epilepsy of Infancy (SMEI) Dravet Syndrome Maria-Fotini a 21/2 years old child is the first and the only child of her parents who are phenotypically healthy and non-consanguinoeus. They are both teachers. Maria-Fotini was deliveredat term (/39/40 weeks of gestation) following her mother’s first uncomplicated pregnancy by emergency caesarean section because of fetal distress. The on set of the labour was spontaneous. Her birth weight was 2900 grms and no resuscitation was required. She was a breast fed baby who has been very healthy making excellent developmental progress. Since the age of three months she has been developing paroxysmal events of various types and duration. The seizures most of the time have focal onset and they become secondarily generalized. They are both febrile and afebrile. However high temperature and hot water during the bath have been proved to be precipitating factors. The parents have made a very informative and detailing diary of the seizures. She presents eyelids myoclonias, jerking of the limbs, generalized tonic clonic movements, and loss of muscle tone – hypotonia with staring. They are occasionally associated by perioral cyanosis and mostly by loss of consciousness. Duration varies from a few seconds up to a few minutes (15-20). She required hospitalization twice for convulsive status epilepticus. She has been also hospitalized on several other occasions in view of repeated seizures on the same day. They occur frequently. She never remained seizures free actually. There was a period of six months during which she developed only febrile events but frequent ones. 1
Maria-Fotini’s seizures deteriorated when we tried Carbamazepine/ Oxcarbamazebine and Lamotrigine. A trial with Pyridoxine was not beneficial either. She is now on treatment with: Valproic Acid (Depakine): 250 mg morning 250 mg night Epitomax (Topamax): 50 mg morning 50 mg night On clinical examination she is a lovely sociable little girl who looks happy. There are no dysmorphic facial features. No birthmarks of any neurocutaneus disorder are found. HC=48,5 cm > 25th centile BW = 13 kg = 25th centile Muscle tone and Muscle power are normal. Deep tendon reflexes are elicited normal and symmetrical on both upper and lower extremities. During her first year of her life developmental progress seemed to be within normal ranges apart from slight delay of gross motor milestones. Mentally she was according to her age, and she has been always alert. However during second year of life global developmental delay was undoubtedly obvious. Maria-Fotini was able to walk independently showing ataxic gait at the age of two years. She is still ataxic. Her fine motor abilities and coordination are impaired too. She is hyperactive with profound attention deficit. She has speech delay development both expressive and receptive language (expressive much more delayed than receptive). They are bilingual at home as her nanny comes from Russia. She can point pictures. She recognizes and shows body parts on request. She understands verbal commands. She can imitate voices of familiar animals. She says only a few words, no phrases, in Greek and in Russian. Laboratory examinations The following tests were carried out and the results were within normal ranges: FBC and Routine biochemistry screening Plasma Lactate CSF Lactate Serum Ammonia levels Plasma Aminoacids Urine Organic Acids CSF viral studies (PCR) (-) and Serology virology (-) 2
EEG performed at the age of five months at Great Ormond Hospital for Sick Children in London was normal. EEG repeated at the age of one year was normal as well. MRI brain at the age of five months was without any abnormalities. MRI brain at the age of one year (08/05/2003): There is evidence of minimal periventricular hyperintensities mainly involving the parietal lobes. In addition there is minimal prominence of the ventricles and extraaxial CSF spaces. No restricted diffusion areas are seen. In conclusion these findings are compatible with parietal minimal ischemic changes. In addition she has developmental delay.
Latest Invastigations I suggested that Maria-Fotini should go to France at a specialized Epilepsy center. Therefore, a Video EEG was performed on the 19/01/05 at Hospital Robert Debre in Paris in the Paediatric Neurology Department under the care of Dr. Alexis Arzimanoglou and was again without any abnormalities. Additionally, genetic studies were carried out for Dravet Syndrom. The results will be ready at the end of March. Dr. Arzimanoglou said that: According to her seizures diary Maria-Fotini seems to have the Dravet Syndrome. On the other hand, she is not mentally delayed. In either case, her future development is expected to me rather bad. On the 26th of February 2005 Maria-Fotini had a status epilepticus (the third one) and required hospitalization for one day. Since then, she has been developing small absences and myoclonic seizures every day, of small duration (only a few seconds). These are counted from 15 –50 per day. OPINION: Maria-Fotini suffers from frequent, resistant seizures (myoclonic, focal and generalized). In addition she has developmental delay. It is obvious that the last two months Maria-Fotini’s seizures are more frequent. CONCLUSION: Since there isn’t any solution to Maria-Fotini’s health problem in Europe I recommend that the child must be transferred to the U.S. for further investigation and treatment. Mayo Clinic is the best appropriate hospital for her situation. I also suggest Cyprus Government cover all the medical expenses. Goula Stylianidou Child Neurologist HOSPITAL ARCBISHOP MAKARIOS III PAEDIATRIC CLINIC NICOSIA-CYPRUS 3