Remote Effects of Malignant Tumors
Although primary CNS neoplasms possess distinct morphologies, clinicians must be aware of paraneoplastic syndromes—remote effects of tumors from other sites on nervous tissue. These occur due to the production of biologically active substances or autoimmune cross-reactions.
The most common manifestation of such effects is peripheral neuropathy. It may develop long before the underlying cancer is diagnosed. Depending on the affected fibers, neuropathy presents in several forms:
- Motor — development of weakness and paresis.
- Sensory — sensory loss, pain, and paresthesias.
- Mixed — a combination of motor and sensory defects.
Lambert-Eaton Myasthenic Syndrome
One of the best-known paraneoplastic disorders is Lambert-Eaton myasthenic syndrome (LEMS). This neuromuscular disorder frequently precedes the diagnosis of malignancy.
Clinical Presentation and Associations The pathology is strongly associated with small cell lung cancer. Neurological symptoms often precede classical respiratory tumor manifestations. The primary clinical sign is pronounced muscle weakness and fatigability. Symptoms predominantly affect the lower extremities, while the arms are significantly less affected.
Pathogenesis The syndrome is rooted in impaired synaptic transmission. Normally, muscle contraction requires the release of the neurotransmitter (acetylcholine) into the synaptic cleft. In Lambert-Eaton syndrome, the following occurs:
- The immune system produces antibodies that mistakenly attack self-tissues.
- Voltage-gated calcium channels located on the presynaptic membrane of the nerve terminal become the target.
- Channel blockade reduces intracellular calcium influx, critically impairing the exocytosis of acetylcholine-containing vesicles.
- Nerve impulses fail to transmit to the muscle, manifesting clinically as muscle weakness.
Differential Diagnosis of CNS Disorders
Because neurological symptoms in tumors are non-specific, they must be differentiated from other broad categories of nervous system diseases characterized by myelin or neuronal destruction:
- Demyelinating pathologies (multiple sclerosis, neuromyelitis optica, Marburg disease). These involve the destruction of normally synthesized myelin with plaque formation and astrogliosis.
- Metabolic disorders. Can be primary (genetic, such as Gaucher, Niemann-Pick, or Wilson disease) or secondary (in the setting of hepatic failure, diabetes, or uremia).
- Toxic encephalopathies. Develop due to toxins (carbon monoxide causes bilateral necrosis of the globus pallidus, methanol causes putaminal necrosis) or ethanol (chronic alcohol abuse leads to Purkinje cell loss and demyelination of cortical fibers).