Neuroleukosis is a complicating leukemia lesion of the nervous system caused by infiltration of nervous structures by leukemic cells. It is manifested by a meningeal symptom complex, signs of intracranial hypertension, focal neurological deficit, peripheral nerve dysfunction. The diagnosis of “neuroleukosis” is established according to neurological examination, analysis of cerebrospinal fluid, cerebral tomography, craniography, examination of bone marrow punctate. Treatment includes the introduction of cytostatics into the spinal space, irradiation of the brain. Effective preventive therapy.
General information
Neuroleukosis (neuroleukemia, NL) is the result of metastasis of leukemic cells in the brain and spinal cord. It is most often a complication of acute lymphoblastic leukemia in children under 15 years of age. Chronic variants of leukemia are complicated by NL much less often than acute ones. Most cases occur during the period of remission of the underlying disease, less often neuroleukosis occurs in the acute phase. It is not uncommon for patients whose symptoms of CNS damage are the first signs of leukemia. The frequency of complications is closely related to the life expectancy of patients (with a rapid course of leukemia, it does not have time to develop). On average, the incidence of NL among patients with leukemia is 5-10%. The introduction of preventive endolumbal infusion of cytostatics into the practice of treatment allowed to reduce the incidence to such a level.
Causes
NL occurs due to secondary damage to the central and peripheral nervous system by cancerous blood cells (myelo-, lymphoblasts). Metastases — infiltrates from blast elements of the blood — can form in the membranes and brain matter, spinal roots, cranial and peripheral nerves. Factors that increase the risk of developing neuroleukemia are the child’s age of the patient, the lymphoblastic form of acute leukemia, high leukocytosis at the onset of the disease, pronounced hepatosplenomegaly.
Pathogenesis
The penetration of leukemic cells into nerve tissues occurs by contact and diapedesis. In the first case, the cells spread to the meninges from the bones of the skull and spine. When the membranes are destroyed, they infiltrate the underlying brain matter. The diapedesis mechanism is caused by the increased permeability of the vessel walls, as a result of which the blasts circulating with the blood flow pass from the vascular bed into the nervous tissue, forming metastatic infiltrates in it. Morphologically, neuroleukosis is characterized by multi-focal leukemic infiltrates, gliosis, and demyelination of nerve fibers. The formation of leukemic foci in the medulla leads to an increase in intracranial pressure, compression of cerebral and spinal structures, loss of functions of the affected area. Infiltration of the ventricular system is dangerous with the development of occlusive hydrocephalus. Infiltrates of nerve trunks cause their dysfunction. Depending on the localization of lesions, a clinical picture is formed, including cerebral and focal symptoms.
Classification
The variety of localization options for leukemic foci leads to a wide variability of clinical symptoms. Therefore , it is proposed to classify neuroleukosis into the following forms:
- Leukemic meningitis is a consequence of leukemic infiltration of the cerebral membranes. Manifests acute meningeal symptoms. It may be the first manifestation of an acute form of leukemia.
- Leukemic meningoencephalitis is the result of a multi—focal lesion of the membranes and medulla. A combination of meningitis, intracranial hypertension, and cranial nerve dysfunction is characteristic.
- The pseudotumorous form is less common. Due to the presence of a local leukemic focus. Simulates the clinic of an intracerebral tumor.
- The peripheral form occurs when infiltrates are localized in the trunks of peripheral nerves. It proceeds according to the type of mono- and polyneuropathies.
The criteria for NL are clinical manifestations and typical changes in cerebrospinal fluid. The presence/absence of these signs formed the basis for the classification of neuroleukemic syndrome into:
- Full — there are clinical symptoms and specific changes in the cerebrospinal fluid.
- Incomplete — there is one of the criteria. Option 1 implies the absence of pathological abnormalities in the cerebrospinal fluid in the presence of clinical manifestations. Option 2 — latent flow against the background of typical disorders of the liquor composition.
- Hidden — there is no clinic, the cerebrospinal fluid is normal. There is swelling of the optic nerve discs during ophthalmoscopy. According to neuroimaging data, focal changes are detected in the cerebral substance.
Symptoms
Cases of meningial and meningoencephalitic forms of NL differ in acute onset. Characterized by intense headache, photophobia, vomiting, increasing lethargy, lethargy. There is an increase in the tone of the occipital muscles. Cranial nerve dysfunction is caused by their direct damage or compression in conditions of growing intracranial hypertension. There may be blurred vision, double vision, strabismus, drooping of the upper eyelid, violation of the friendly movement of the eyeballs, facial asymmetry, hearing disorder. Epileptic seizures are possible.
In the pseudotumor variant, neuroleukosis occurs with a predominance of focal symptoms. Depending on the location of the lesion site, unilateral limb weakness (hemiparesis), speech impairment (motor aphasia), extrapyramidal symptoms (hyperkinesis), attacks of Jackson’s epilepsy with convulsions or sensory disorders of 1-2 limbs are observed. The peripheral form is characterized by paresthesia, decreased sensitivity, muscle weakness, and a decrease in tendon reflexes in the innervation zone of the affected nerves. Manifestations may indicate a limited lesion of one nerve trunk (for example, tibial neuropathy).
Complications
The increase in leukemic infiltration in the central nervous system leads to the death of neurons with the aggravation of neurological abnormalities and the formation of irreversible disorders. A serious complication is compression of the brain due to growing intracranial hypertension (including by the mechanism of occlusive hydrocephalus). The mass effect with compression of the cerebral trunk provokes a disorder of vital functions, acts as a cause of death.
Diagnostics
The interpretation of neurological symptoms in patients with established leukemia does not cause diagnostic difficulties. The difficulties of diagnosis are associated with cases when neuroleukosis has a latent course or is a variant of the debut of hemoblastosis. The diagnostic algorithm includes:
- Neurologist’s examination. It allows to identify the rigidity of the muscles of the occiput, meningial symptoms of Brudzinsky, Kernig, motor and sensory disorders, speech disorders, pathology of peripheral and cranial nerves. The results obtained allow us to determine the type and level of NS lesion.
- Radiography of the skull. Determines osteoporosis and porosity of the bones of the arch in patients with a latent form of NL.
- Examination of cerebrospinal fluid. The material is obtained by lumbar puncture. Neuroleukosis is characterized by an increase in the number of cellular elements (cytosis) over 5 cells / ml, the presence of blast cells in the cerebrospinal fluid. Similar changes are observed in 90% of patients.
- Tomographic studies. Neuroimaging methods are crucial in cases of latent neuroleukemia, when detecting changes in cerebrospinal fluid without an appropriate disease clinic. CT of the brain visualizes the foci of infiltration as hypodensive. Brain MRI confirms the presence of infiltrates, allows you to more accurately assess their size and location. However, neuroimaging does not diagnose the nature of infiltrates, therefore it is interpreted in combination with other diagnostic data.
- Sternal puncture. It is necessary to obtain a bone marrow sample and its subsequent analysis. The results of the myelogram allow us to confirm the presence of leukemia, to assess the state of hematopoiesis.
Neuroleukosis must be differentiated from brain tumors, meningitis and encephalitis of infectious etiology, the peripheral form — from Guillain-Barre syndrome, polyneuropathies of a different genesis.
Treatment
The therapy is carried out by specialists in the field of hematology and neurology with the participation of radiologists. The difficulties of treatment are due to the poor permeability of the blood-brain barrier for antitumor pharmaceuticals. The basic method is the endolumbal administration of cytostatics (methotrexate) in combination with cranial irradiation. During the treatment, complete rehabilitation of the cerebrospinal fluid is achieved. Radiation therapy contributes to the death of the formed tumor infiltrates. According to the indications, an antitumor drug (cytarabine) or a glucocorticosteroid (prednisone) is additionally administered together with a cytostatic. Intrathecal administration is canceled after three times obtaining normal results of the analysis of the cerebrospinal fluid.
Side neurotoxic effects of cytostatic and radiological therapy may cause a temporary deterioration in the general condition of the patient. Along with basic therapy, relief of adverse reactions, symptomatic therapy with anticonvulsants, dehydrating agents, etc. is carried out.
Prognosis and prevention
Usually, complex active treatment allows to achieve regression of neurological symptoms within 3-4 weeks. Further prognosis is closely related to the course of the underlying disease. Often, timely preventive therapy can prevent neuroleukosis, which is recommended to begin during the induction of remission. Preventive therapy includes a course of endolumbal administration of a cytostatic drug with repeated single infusions during reinduction treatment.