Perisylvian syndrome

Overview

Perisylvian syndrome, more formally known as Bilateral Perisylvian Polymicrogyria (BPP), is a rare neurological disorder characterized by abnormal development of the cerebral cortex, specifically in the perisylvian region of the brain. This region encompasses the area surrounding the Sylvian fissure, which plays a crucial role in speech, language, and motor control of the face and throat. The term "polymicrogyria" refers to the presence of an excessive number of small, abnormally formed gyri (folds) in the cerebral cortex. The syndrome is associated with a wide range of symptoms including developmental delays, epilepsy, speech and swallowing difficulties, and oromotor dysfunction. Severity varies from mild to profound, depending on the extent and symmetry of cortical malformation.

Causes

Perisylvian syndrome is caused by disrupted neuronal migration during fetal brain development, typically occurring between the 12th and 24th week of gestation. The underlying causes may be genetic, environmental, or unknown. Several genes have been implicated in the development of polymicrogyria, including:

• SRPX2: Associated with X-linked forms of perisylvian syndrome, especially those involving epilepsy and language delay

• GPR56, TUBB2B, PAX6: Other gene mutations linked to polymicrogyria and related cortical malformations

In addition to genetic mutations, possible environmental causes or contributing factors may include:

• Prenatal infections (e.g., cytomegalovirus)

• Fetal hypoxia or ischemia

• Exposure to toxins or drugs during pregnancy

In many cases, the exact cause remains idiopathic, especially when no genetic abnormality is identified.

Symptoms

The clinical features of Perisylvian syndrome depend on the severity and extent of cortical malformation, as well as whether one or both hemispheres are affected. Common signs and symptoms include:

Neurological and Motor Symptoms:

• Seizures: Epilepsy is common and may be focal, generalized, or drug-resistant

• Oromotor dysfunction: Difficulty in coordinating muscles of the mouth and throat, affecting feeding, swallowing, and facial expression

• Hypotonia or spasticity: Decreased or increased muscle tone, often affecting facial and limb muscles

• Dysarthria: Poor articulation of speech due to oromotor deficits

Speech and Language Impairments:

• Developmental speech delay: Ranges from mild delays to complete absence of speech

• Aphasia: Language comprehension and expression deficits, more severe in bilateral involvement

Cognitive and Behavioral Symptoms:

• Learning disabilities or intellectual disability

• Behavioral disturbances, including hyperactivity or social difficulties

Additional features may include excessive drooling, feeding difficulties in infancy, and facial weakness. The presentation can overlap with conditions like cerebral palsy, especially in children with prominent motor symptoms.

Diagnosis

Diagnosis of Perisylvian syndrome relies on clinical evaluation combined with advanced neuroimaging and genetic testing. Key steps in the diagnostic process include:

• Neurological examination: To assess motor function, cranial nerve involvement, and speech/language abilities

• Magnetic Resonance Imaging (MRI): The gold standard for diagnosis; reveals polymicrogyria in the perisylvian regions, appearing as irregular thickening and multiple small gyri

• Electroencephalogram (EEG): Used to detect epileptic activity and characterize seizure types

• Genetic testing: May identify mutations in known polymicrogyria-associated genes (e.g., SRPX2, GPR56)

• Speech and developmental assessments: Evaluate the degree of oromotor and cognitive involvement

Early diagnosis is crucial for initiating therapy and improving developmental outcomes.

Treatment

There is no cure for Perisylvian syndrome, and treatment focuses on managing symptoms, improving quality of life, and supporting developmental progress. A multidisciplinary approach is essential, involving neurology, speech therapy, occupational therapy, physical therapy, and special education.

Management Strategies:

• Anti-epileptic drugs (AEDs): Used to control seizures; some children may require multiple medications or surgery for drug-resistant epilepsy

• Speech and language therapy: Key for improving communication skills; may include augmentative and alternative communication (AAC) devices in nonverbal children

• Feeding therapy: To address swallowing difficulties and ensure adequate nutrition

• Physical and occupational therapy: To enhance motor skills, reduce muscle tone abnormalities, and improve daily functioning

• Educational support: Individualized education programs (IEPs) tailored to the child’s cognitive and behavioral needs

Surgical interventions such as vagus nerve stimulation or focal cortical resection may be considered in cases of intractable epilepsy.

Prognosis

The prognosis for individuals with Perisylvian syndrome depends on the severity and extent of cortical involvement. Children with unilateral and less extensive polymicrogyria may have milder symptoms and near-normal development. Those with bilateral or widespread involvement often face significant challenges, including lifelong speech impairments, intellectual disabilities, and drug-resistant epilepsy.

With early intervention and comprehensive care, many children make meaningful developmental gains and learn to communicate effectively, even if speech remains limited. Seizure control is an important determinant of quality of life. Ongoing therapy and educational support are typically required throughout childhood and adolescence. Genetic counseling is recommended for families, particularly if a genetic mutation is identified.