Treatment
While there is no current cure, the treatments for Chiari malformation are surgery and management of symptoms, based on the occurrence of clinical symptoms rather than the radiological findings. The presence of a syrinx is known to give specific signs and symptoms that vary from dysesthetic sensations to algothermal dissociation to spasticity and paresis. These are important indications that decompressive surgery is needed for patients with Chiari Malformation Type II. Type II patients have severe brain stem damage and rapidly diminishing neurological response.Decompressive surgery involves removing the lamina of the first and sometimes the second or third cervical vertebrae and part of the occipital bone of the skull to relieve pressure. The flow of spinal fluid may be augmented by a shunt. Since this surgery usually involves the opening of the dura mater and the expansion of the space beneath, a dural graft is usually applied to cover the expanded posterior fossa.A small number of neurological surgeons believe that detethering the spinal cord as an alternate approach relieves the compression of the brain against the skull opening (foramen magnum), obviating the need for decompression surgery and associated trauma. However, this approach is significantly less documented in the medical literature, with reports on only a handful of patients. The alternative spinal surgery is also not without risk.Complications of decompression surgery can arise. They include bleeding, damage to structures in the brain and spinal canal, meningitis, CSF fistulas, occipito-cervical instability and pseudomeningeocele. Rare post-operative complications include hydrocephalus and brain stem compression by retroflexion of odontoid.
The trials were conducted in the United States and Canada.Trial 1 enrolled subjects 1 to 20 years old who were recently diagnosed with ALL or lymphoblastic lymphoma. Subjects received calaspargase pegol-mknl or pegaspargase (a drug that helps convert asparagine to other substances) as part of a combination of drugs used for treatment of ALL. The trial had 2 phases. Subjects received calaspargase pegol-mknl or pegaspagase intravenously on Day 7 of the first phase. Subjects received either calaspargase pegol-mknl intravenously every 3 weeks for 10 doses or pegaspargase intravenously every 2 weeks for 15 doses during the second phase. The benefit of calaspargase pegol-mknl was assessed by measuring the activity level of asparginase in the blood on Days 7, 11, 18, 25, and 32 of the first phase and comparing it to pegaspargase.Trial 2 enrolled subjects 1 to 18 years old who were recently diagnosed with high-risk ALL. Subjects received one of 2 doses of calaspargase pegol-mknl or pegaspargase intravenously as part of a combination of drugs used for treatment. Subjects received calaspargase pegol-mknl or pegaspargase on Day 4 of the first phase and Days 2 and 22 of the second phase. Subjects received up to 12 doses of calaspargase pegol-mknl or pegaspargase intravenously depending on the bone marrow response. The benefit of calaspargase pegol-mknl was assessed by measuring the concentration of drug in the body over 25 days (AUC) and the maximum amount of drug in the blood after a single dose (Cmax).