I. Pathological basis of neurological damage: Cerebral cortex and subventricular nodules are seen in 90% of patients. They form during embryogenesis. The most common abnormal cells in the nodules are large dysplastic neuronal cells, glial cells, and abnormal astrocytes. It is commonly believed that cortical nodules are the main cause of epilepsy and mental retardation, and surgical removal of the nodules results in a significant reduction in seizures in patients. There are more extensive scattered abnormal cells in the cortex that are not detected by MRI. This non-nodular abnormality may also lead to seizures. Subventricular nodules are usually asymptomatic, of which 5 ~ 15% may develop into giant cell type astrocytomas, which may lead to progressive hydrocephalus and even death. II. Clinical manifestations: 1. Epilepsy is seen in 60-90% of patients. Epilepsy usually begins within 1 year of the patient’s birth. In infancy, seizures often present as partial seizures and strings of spasmodic seizures. Unilateral tonic or clonic phenomena may appear at 3 to 4 months of life and are often overlooked until the onset of infantile spasms. Tonic eye deflection, head turning, and asymmetric involvement of limbs may be seen. Partial seizures may precede, coincide with, or progress to infantile spasms. In TSC infantile spasms of focal origin confirmed by VEEG: focal discharge-induced infantile spasms, PET reveals hypometabolism of the focal cortex. Seizure termination was seen after partial cortical excision. Nodules of calcified cortex were seen on head CT. Almost all patients with infantile spasms later develop other types of seizures. more than 50% have multiple types of seizures. the EEG shows multifocal abnormalities with bilaterally synchronized spike-and-slow wave synthesis, similar to the L-G syndrome. Early onset seizures are an independent risk factor for mental retardation. Seizures should be treated immediately and adequately to control them in order to stop the progression of epileptic encephalopathy and mental retardation. VGB, an inhibitor of GABA aminotransferase, is 95% effective in treating TSC-related infantile spasms. However, after a period of remission of infantile spasms, other types of seizures may occur in childhood. 12% of adults with TSC develop new-onset seizures. Combination medication is needed after failure of monotherapy. Topiramate with multiple mechanisms of action is available. Levetiracetam or valproate and lamotrigine, which enhance GABAergic inhibition, can be combined. A balance between benefit and drug side effects should be observed. Therapeutic advances: Recent studies have identified rapamycin as an mTOR inhibitor, and clinical studies have shown that oral rapamycin can inhibit the progression of astrocytomas associated with TSC. Animal studies of TSC have shown that mTOR inhibitors can stop the progression of epilepsy and significantly improve cognitive function. Animal experiments have also shown that rapamycin and its derivatives may be useful in ameliorating the clinical symptoms of a variety of TSCs, including skin lesions, lymphangioleiomyomatosis, and renal angiomyolipoma. Its therapeutic effect on TSC is currently being evaluated through preclinical and clinical phase trials. 2. Mental retardation is very common, with approximately 30% of patients presenting with severe mental retardation and the remaining 70% ranging from mild to moderate mental retardation to normal intelligence. About 50% of patients have IQ > 80 points. It may be related to temporal lobe nodules. Autism is seen in 25% of patients. Attention deficit hyperactivity disorder (ADHD) is seen in 50% of patients. In adults with TSC, 55% ~ 59% of patients suffer from anxiety and depression. 3. Developmental and learning disorders include developmental delay (40-60%), learning difficulties (40-60%) and are common in patients with infantile spasms and epilepsy.