What is the prognosis for survival in patients with lissencephaly (a rare brain formation disorder)?

From the Guidelines

Survival in lissencephaly is significantly influenced by the severity of the condition, with life expectancy ranging from a few years to adulthood, and management should focus on supportive care to optimize quality of life and potentially extend survival. The severity of lissencephaly is classified based on the grade and gradient of the gyral malformation, cortical thickness, and presence of associated brain malformations 1. Children with severe forms of lissencephaly, such as complete agyria, often have shorter lifespans due to complications like respiratory infections, seizures, and feeding difficulties. In contrast, milder forms like pachygyria or subcortical band heterotopia may allow for longer survival.

Key aspects of management include:

• Anticonvulsant medications like levetiracetam (10-60 mg/kg/day), valproic acid (10-60 mg/kg/day), or phenobarbital (3-5 mg/kg/day) to control seizures
• Gastrostomy tube placement for nutritional support
• Respiratory care including positioning, suctioning, and sometimes ventilatory support
• Physical, occupational, and speech therapies to maximize developmental potential Regular follow-up with a multidisciplinary team including neurology, pulmonology, gastroenterology, and rehabilitation medicine is essential for optimizing quality of life and potentially extending survival. The underlying cause of reduced survival in lissencephaly is the significant brain malformation characterized by absent or reduced brain folds (gyri), affecting multiple neurological functions including motor control, feeding coordination, and respiratory regulation 1.

It's also important to consider the genetic basis of lissencephaly, as it is considered an exclusively genetic disorder with 28 genes currently known to be associated with this condition 1. Understanding the genetic cause can help in predicting the severity and guiding the management of the condition. However, the primary focus should always be on providing supportive care to improve the quality of life and survival of individuals with lissencephaly, as the condition's severity and associated complications are the most significant predictors of outcome 1.

From the Research

Survival in Lissencephaly

• Survival in lissencephaly is related to the severity of the condition on neuroimaging, as shown in a study published in 2011 2.
• The study found that life expectancy was related to the severity of the lissencephaly, with more severe cases having a poorer prognosis.
• Another study published in 2010 discussed the different forms of lissencephaly and their wide heterogeneity, as well as the complex involvement of several organs 3.
• A study published in 2016 found that patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year 4.
• The same study found that lamotrigine and valproate were the most successful treatments for epilepsy in these patients, with good or partial response rates in 88-100% of patients.

Clinical Characteristics and Management

• Lissencephaly is characterized by severe intellectual disability, intractable epilepsy, and complete dependency on care 2.
• The condition involves not only the brain but also several other organs and districts, including eyes, face, muscles, genital organs, heart, and bones 3.
• A review published in 2021 provided an update on diagnostics and clinical management of lissencephaly, including the use of molecular genetics and MRI imaging 5.
• The review also discussed the importance of clinical follow-up recommendations and available data on epilepsy management in patients with lissencephaly.

Treatment and Prognosis

• A study published in 2022 found that levetiracetam may be preferred for seizure prophylaxis in patients with supratentorial neurosurgical diseases, but its efficacy in other conditions such as traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage is unclear 6.
• The study found that levetiracetam was associated with a lower risk of adverse events compared to other antiseizure medications.
• Overall, the prognosis for patients with lissencephaly is generally poor, with a high risk of seizures, intellectual disability, and other complications 4, 2.