The correlation of the clinical features with magnetic resonance imaging findings in patients with Agyria-Pachygyria complex

SUMMARY The Correlation of the Clinical Features with Magnetic Resonance Imaging Findings in Patients with Agyria-Pachygyria Complex The term agyria-pachygyria is applied to several disorders of neuronal migration anomalies that result in total or subtotal absence of cortical sulci and severely disturbed architectonics of the cortical plate. The cause of the migrational arrest that lead to agyria- pachygyria complex is unknown. Information regarding the clinical prognosis of focal anomalies of neuronal migration in various cortical lesions is scarce. The aim of this study is to determine the spectrum of clinical findings in agyria-pachygyria complex, identify possible causes and correlate the clinical features with the extent of the lesions on MRI. Material and Methods: We studied 37 patients with agyria-pachygyria complex in Dokuz Eylül University Department of Pediatric Neurology. A standart detailed form, emphasizing abnormalities of pregnancy, associated malformations, family history, presence of seizures, age of onset, type, frequency, response to treatment and course of the epilepsy, EEG findings, type of motor deficit and area of body involved, developmental level in patients younger than 6 years of age (assessed by the Ankara Developmental Screening Test) and intelligence quotient in older patients older than 6 years of age (assessed by Wechsler Intelligence Scale for Children-Revised). On the basis of the MRI features, the patients were separated in two groups: Group 1 (18 children) showed generalized or bilateral gyral malformation. Group 2 (19 children) showed localized or unilateral gyral malformation. Results: The patient's ages ranged from 1 day to 15 years at the time of presentation and 2 months to 15 years at the time of MRI (mean age 1.7 years, 4.1 years respectively). Twenty-two patients (59.5%) were male and 15 (40.5%) were female. The number of male patients were significantly higher in group 1 compared with group 2. Pregnancies were normal in the mothers of all but eleven patients (29.7%). These events were maternal serious upper airway infection with fever (2 patients), excessive smoking (2 patients), vaginal bleeding (2 patients), drug exposure (3 patients), serious psychologic trauma in first 4 months of pregnancy (1 patient) and intrauterin CMV infection (1 patient). Associated genetic syndromes were present in 13.5% of patients. One patient in group 1 had facial anomalies leading to the diagnosis of Miller-Dieker syndrome. In group 2, 4 patients were diagnosed with various genetic syndromes. Karyotype was done for 10 patients, but showed no abnormalities. The rate of consanguinity was 27% without any significantdifference between the two groups. Family history of neurologic disorders was positive by 7 patients (18.9%). The clinical presentation of the subgroups were diverse. Patients in group 2 presented much more with seizures, where patients in group 1 often presented with developmental delay, microcephaly and seizures. Seizure disorders were present in 28 (75.7%) patients. Eighteen (64.3%) had generalized seizures and the remaining 10 (35.7%) had partial seizures. The ratio of generalized seizures in group 1 is significantly higher, where partial seizures were more common in group 2. Age at onset of seizures ranged from birth to 15 years without any significance between the two groups (mean 2.13 years of age). The patients in group 1 had seizure frequency significantly more than group 2 patients. Of the 28 patients, 21 (75%) were good-responders to antiepileptic treatment. By the remaining 7 (25%) patients the seizures were reduced only less than %50 despite excessive treatment. Eleven patients (39.3%) were receiving the treatment with a single antiepileptic drug. Seventeen (60.7%) required two or more drugs. All of the 7 patients with poor seizure control were taking two or more antiepileptic drugs, where only 47.6% of good-responders were taking polytherapy. Regarding the EEG findings, 18 (48.6%) patients had generalized or multifocal epileptiform abnormality, 15 (40.5%) showed focal epileptiform activity and the remaining 4 (10.8%) patients had normal EEG findings. Generalized or multifocal abnormalities were significantly more common in group 1 and focal abnormalities in group 2. Neurological deficits in group 2 patients were seen as frequent as in group 1 patients, but hemiparesias contrlateral to the affected side was the most frequent neurologic deficit by group 2 patients. Spastic quadriparesis and microcephaly were more common in group 1. All patients but two, concerning to group 2, had developmental delay or mental retardation mild to severe in degree. Conclusion: The extent and distribution of agyria-pachygyria complex vary widely and the clinical features are accordingly very diverse. Patients with bilateral and generalized gyral anomalies have a poor prognosis for intellectual development, outcome of epilepsy and neurologic disability. The recognition of these lesions with higher-resolution techniques of MRI is important for planning proper treatment and genetic counseling. Key words: Agyria-pachygyria, etiology, clinical finding, epilepsy, MRI