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Leptomeningeal disease

Leptomeningeal disease (LMD), also known as leptomeningeal carcinomatosis, is a rare and serious condition in which cancer cells from a tumor are disseminated to the leptomeninges (thin layers of tissue that cover the brain and spinal cord). LMD can result from most types of cancer but breast cancer, lung cancer, and melanoma, as well as some non-solid cancers, are more common among patients with LMD.

 

Approximately one in five of all solid tumor patients develop this complication/condition but it is not clinically diagnosed in about half of these patients. The incidence of LMD is rising due to improvements in its diagnosis. The prognosis for LMD is poor and the patients survive for only about 3 months despite active treatment.

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Symptoms

Symptoms of LMD are related to raised intracranial pressure (due to the buildup of fluid in the skull), nerve dysfunction, and cerebellar dysfunction. Some of the symptoms are:

  • Headaches

  • Lethargy

  • Seizures

  • Blurry vision

  • Back pain

  • Difficulty in keeping a normal posture

  • Difficulty in swallowing food

  • Changes in mental function

Diagnosis

Diagnosing LMD can be challenging, as the symptoms and some clinical findings overlap with other conditions, such as neurosarcoidosis, chronic meningitis, and Guillain-Barre syndrome, and can be difficult to distinguish. LMD is suspected in advanced cancer or systemic disease patients showing the neurological symptoms mentioned above. The diagnostic workup consists of neuroimaging studies, using magnetic resonance imaging (MRI) and computed tomography (CT), and the evaluation of the cerebrospinal fluid (CSF).

  • Imaging-based approaches: The standard of care imaging modality is gadolinium-enhanced MRI. The sensitivity of MRI is variable. Therefore, CSF evaluation is required to further strengthen the diagnosis.

  • CSF examination: CSF is obtained through a spinal tap. It is analyzed for the presence of cancer cells and some other biomarkers such as vascular endothelial growth factor (VEGF). All patients have some abnormalities in their CSF which can potentially be exhibited in the diagnosis. New biomarkers are being investigated to facilitate the diagnosis of LMD.

Management

The management strategy of LMD is based on the clinical condition of the patient. If their overall condition is poor, only palliative care is preferred. Palliative care aims to reduce the symptoms and improve the quality of life of the patient. It does not reverse or slow down the progression of the underlying disease. Palliative care consists of surgery to install a ventriculoperitoneal shunt that lowers intracranial pressure and includes medications that help to manage headaches, seizures, and mental illnesses.

 

Active therapy is given to patients who have better conditions and are healthy enough to withstand the burden of aggressive therapy. This consists of chemotherapy and radiotherapy.

 

  • Chemotherapy: Chemotherapy for LMD can be given systemically (through an IV injection) or intrathecally (through a spinal tap). Both of these delivery methods have their challenges that complicate the management of LMD. These challenges arise from the resistance of the tumor cells to a wide variety of chemotherapeutic drugs, poor penetration of the systemic drug into the leptomeningeal compartment, and less than the optimum distribution of the drug throughout the leptomeningeal compartment due to the obstruction caused by the tumor masses.

 

  • Radiation therapy: Various types of radiotherapy can be utilized in the management of LMD. These are involved-field radiotherapy, whole-brain radiotherapy, and craniospinal irradiation. The specific type of radiotherapy utilized depends upon whether the target is tumor masses or free-floating tumor cells in the CSF and which part of the body is being targeted. Some challenges of radiotherapy are its limited efficacy and extensive toxicities.

 

In a nutshell, LMD is a serious and often difficult-to-treat condition that can have a major impact on a person's health and quality of life. More research is needed to improve our understanding of the causes, diagnosis, and treatment of this condition.

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