Non-Hodgkin’s lymphoma (NHL) can affect long-term brain health in several complex and interconnected ways, especially when the lymphoma involves the central nervous system (CNS) directly or indirectly. The impact on brain health arises from the disease itself, its spread to the brain, and the treatments used to combat it.
When NHL involves the brain or spinal cord, it is often referred to as primary central nervous system lymphoma (PCNSL). This form of lymphoma originates in the CNS and can cause symptoms such as memory problems, confusion, mood changes, difficulty speaking, weakness on one side of the body, seizures, and other neurological deficits. Because PCNSL affects brain tissue directly, it can disrupt normal brain function, leading to cognitive impairments and neurological symptoms that may persist long after treatment[3][4].
Even when NHL does not start in the CNS, it can spread there (secondary CNS lymphoma), causing similar neurological problems. The presence of lymphoma cells in the brain or spinal cord can increase intracranial pressure, cause inflammation, and damage neural tissue, all of which contribute to long-term brain dysfunction[2].
Beyond the direct effects of lymphoma cells in the CNS, the treatments used to manage NHL, including chemotherapy, radiation, and immunotherapy, can have significant neurotoxic effects. Chemotherapy, especially high-dose methotrexate used in PCNSL, can cross the blood-brain barrier and affect brain cells, sometimes causing what is known as “chemo brain.” This condition involves memory loss, difficulty concentrating, slowed thinking, and problems with executive functions like planning and multitasking. These cognitive impairments can last months or even years after treatment ends[1].
Radiation therapy to the brain, often used in PCNSL or when lymphoma spreads to the CNS, can also cause long-term damage. Radiation can lead to inflammation, damage to blood vessels, and loss of healthy brain cells, which may result in cognitive decline, problems with balance and coordination, and other neurological deficits. The risk and severity of these effects tend to increase with higher doses and larger areas of brain exposure.
Another important factor is the systemic inflammation and metabolic disturbances caused by both the lymphoma and its treatment. Cancer and its therapies can disrupt the blood-brain barrier, allowing harmful substances and immune cells to enter the brain and cause neuroinflammation. This inflammation can damage neurons and supporting brain cells, contributing to cognitive decline and neurological symptoms. Additionally, metabolic imbalances such as deficiencies in vitamin B12 or folate, or electrolyte disturbances, can worsen brain function and increase vulnerability to neurological damage[1].
Paraneoplastic neurological syndromes (PNS) are another way NHL can affect brain health. These are rare immune-mediated conditions where the body’s immune response to lymphoma mistakenly attacks the nervous system, leading to rapid and severe neurological problems. PNS can cause symptoms ranging from memory loss and confusion to seizures and movement disorders, and they often require specialized treatment to control the immune response[1].
Long-term brain health in NHL survivors is also influenced by the patient’s age, overall health, and the presence of other conditions such as heart failure, which can complicate treatment and recovery. For example, heart failure can limit the use of certain chemotherapy drugs due to their potential to worsen cardiac function, which indirectly affects brain health by limiting treatment options or causing additional systemic stress[4].
In summary, non-Hodgkin’s lymphoma affects long-term brain health through direct invasion of the CNS by lymphoma cells, neurotoxic effects of treatments like chemotherapy and radiation, systemic inflammation and metabolic disturbances, and immune-mediated neurological damage. These factors can lead to persistent cognitive impairments, neurological deficits, and reduced quality of life for survivors. Careful management of the disease and its treatment, along with monitoring and addressing neurological symptoms early, is crucial to preserving brain health over the long term.
