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Chemotherapy-Induced Neurotoxicity
“The prevalence of chemotherapy-induced neurotoxicity (CIN) varies from 19% to more than 85%, with the highest reported for platinum compounds (70–100%) and taxanes (11–87%) [4].”
Hi. My name is David Emerson. I am a long-term multiple myeloma survivor. I’ve been struggling with various forms of CIN since I completed my autologous stem cell transplant in late 1995. Actually, I think I began to notice symptoms several years following my ASCT but my memory is hazy as to what symptoms began, when.
I didn’t understand my symptoms at the time but lower body weakness and chemobrain were early signs of chemotherapy-induced neurotoxicity. This post is dedicated to the full spectrum of CIN symptoms-
- Peripheral Neuropathy
- Chemobrain
- CNS Toxicity
My goal in researching and writing this post is to try to reach out to any cancer survivors who recognize symptoms discussed below that may apply to them. Please read all the way to the bottom of this post.
While my chemobrain has improved greatly, I can only say that my lower body weakness has almost stabilized. I can’t say that I’ll be running a marathon anytime soon.
Understanding Chemotherapy-Induced Neurotoxicity
Chemotherapy agents, while designed to target rapidly dividing cancer cells, can inadvertently affect normal cells, particularly those with high metabolic rates. This includes neurons and glial cells within the central and peripheral nervous systems. Consequently, patients may experience a range of neurological symptoms, which can be acute, subacute, or chronic in nature.
Types of Chemotherapy-Induced Neurotoxicity
- Peripheral Neuropathy: Peripheral neuropathy is the most common form of CIN. It manifests as pain, numbness, tingling, or weakness in the extremities, often beginning in the fingers and toes and progressing proximally. This condition is primarily associated with drugs like paclitaxel, vincristine, and cisplatin.
- Cognitive Dysfunction: Chemotherapy-induced cognitive dysfunction, commonly referred to as “chemo brain,” is a less understood but significant aspect of CIN. Patients may experience difficulties with memory, concentration, and executive functions. These effects can persist long after treatment cessation, significantly impacting the quality of life.
- Central Nervous System Toxicity: Certain chemotherapy agents, such as methotrexate, can penetrate the blood-brain barrier, potentially leading to more severe neurotoxic effects. This can result in a range of symptoms, including headaches, seizures, and altered mental status.
Mechanisms of Chemotherapy-Induced Neurotoxicity
The precise mechanisms underlying CIN are multifaceted and not entirely elucidated. However, several key factors contribute to its development:
- Oxidative Stress: Chemotherapy agents induce oxidative stress within neurons, leading to an imbalance between reactive oxygen species and antioxidant defenses. This disrupts normal cellular function and can ultimately lead to neuronal damage.
- Disruption of Axonal Transport: Certain drugs, such as vincristine, interfere with axonal transport, disrupting the flow of essential molecules and organelles within neurons. This impairs the communication between nerve cells and can result in peripheral neuropathy.
- Inflammation and Immune Response: Chemotherapy-induced inflammation can stimulate an immune response within the nervous system. This can lead to the release of pro-inflammatory cytokines, which further contribute to neuronal damage and dysfunction.
Mitigation and Management of Chemotherapy-Induced Neurotoxicity
- Dose Modification and Drug Substitution: Individualized dosing regimens and the use of alternative chemotherapy agents with lower neurotoxic profiles can help minimize the risk of CIN while maintaining treatment efficacy.
- Neuroprotective Agents: Certain pharmaceuticals, such as antioxidants and neurotrophic factors, have shown promise in preclinical studies for mitigating CIN. Clinical trials are underway to evaluate their effectiveness in humans.
- Physical and Occupational Therapy: Physical and occupational therapy can be valuable in managing peripheral neuropathy. Exercises that focus on balance, coordination, and strength can help improve function and alleviate symptoms..
Nerve Conduction therapies that I’ve tried. As I mentioned above, I can’t boast of any amazing cures. Only moderate improvements.
- Exercise
- Acupuncture
- Acetyl-l-Carnitine
- Alpha-lipoic acid
- cytidine diphosphate-choline (CDP Choline),
Are you a cancer survivor experiencing any of the symptoms of chemotherapy-induced neurotoxicity? Let me know- David.PeopleBeatingCancer@gmail.com.
Thanks,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
A review of movement disorders in chemotherapy-induced neurotoxicity
“Chemotherapy agents used in the standard treatments for many types of cancer are neurotoxic and can lead to lasting sensory and motor symptoms that compromise day-to-day movement functions in cancer survivors. To date, the details of movement disorders associated with chemotherapy are known largely through self-reported symptoms and functional limitations. There are few quantitative studies of specific movement deficits, limiting our understanding of dysfunction, as well as effective assessments and interventions…
Chemotherapy agents used in the standard treatments for many types of cancer—including
- platinum compounds,
- taxanes, and
- vinca alkaloids—
exhibit neurotoxic adverse effects. Depending on individual compounds, chemotherapy can damage the nervous system via various mechanisms…
These adverse effects are commonly referred to as chemotherapy-induced peripheral neuropathy or neurotoxicity (CIPN). Although the ‘P’ in CIPN is included to describe damage to the peripheral nervous system, there is also evidence of central neurotoxicity [2, 3].
To acknowledge the central involvement that is not captured by peripheral neuropathy, we adopted CIN as chemotherapy-induced neurotoxicity for this review…
Sensory symptoms associated with chemotherapy are most common and may include:
- numbness/tingling,
- neuropathic pain,
- increased sensibility to hot/cold temperatures, and
- decreased vibration and pinprick sensitivity.
Motor symptoms may include hyporeflexia, weakness, and muscle cramps. Autonomic symptoms, although less common, may include dizziness, hearing loss, and constipation [5, 6]. CIN symptoms can present immediately or progress after several cycles of treatment, and their severity usually increases with drug accumulation…
These symptoms often improve over time after treatment cessation but can persist for years in a subset of patients, limiting their quality of life across the entire cancer illness trajectory [7,8,9,10]. A major issue associated with these sensory and motor symptoms is compromised movement function that contributes to functional impairments in day-to-day tasks [11, 12]…
This evidence suggests that cancer survivors with CIN are unstable in standing…
As a compensatory strategy, cancer survivors increase the weight of the visual and vestibular systems, but the summarized evidence indicates that this strategy compensates incompletely for the deficits in the somatosensory system during static standing…
Falls are common in cancer survivors. It is estimated that about 30% of cancer survivors fall every year [48], and individuals with CIN symptoms are 1.7–1.8 times more likely to fall than the asymptomatic individuals [7, 49]…
Similar to postural instability, this impaired gait pattern was shown to be associated with CIN-related neuropathy…
Overall, cancer survivors with chemotherapy-induced neurotoxicity have been shown to present with increased postural sway, conservative gait patterns, and suboptimal hand function, but the current understanding of CIN-related movement function changes is far from comprehensive…
There are currently no effective treatments for CIN. Many early reports suggest a possible beneficial effect of exercise (see reviews [11, 78, 79]). However, most exercise studies took a multimodal approach…
Cancer Survivors Face Peripheral Neuropathy Years After Chemotherapy
“The authors also found few studies that tracked long-term peripheral neuropathy, which may leave physicians and patients uninformed about the condition, according to the study…
“The most striking finding from the review was how little data was out there,” Dr Melnikow said. “And these studies report a wide range of frequency for peripheral neuropathy, from as low as 11% to more than 80% of patients at 1 to 3 years after treatment…”
Mechanisms of Chemotherapy-Induced Neurotoxicity
“Many widely used chemotherapy drugs including:
- platinum-based agents,
- taxanes,
- vinca alkaloids,
- proteasome inhibitors, and
- thalidomide analogs
may cause direct and indirect neurotoxicity…
Chemotherapy-induced peripheral neuropathy
According to the WHO rating scale, a
- grade 0 corresponds to no symptoms of neuropathy,
- grade 1 corresponds to paresthesias (a tingling, tickling or prickling sensation) and/or decreased tendon reflexes,
- grade 2 corresponds to severe paresthesias and/or mild weakness,
- grade 3 corresponds to intolerable paresthesias and/or marked motor loss and
- grade 4 corresponds to paralysis.