Makindo Medical Notes

Related Subjects: | Anti-NMDA (NMDAR) Receptor Encephalitis | Herpes Simplex Encephalitis (HSV) | Acute Encephalitis | Limbic Encephalitis | Paraneoplastic Limbic Encephalitis (Dementia) | Hashimoto's (Steroid Responsive) Encephalopathy | Acute Disseminated Encephalomyelitis | Dementias

About Paraneoplastic Limbic Encephalitis (Dementia)

• Definition: Paraneoplastic Limbic Encephalitis (PLE) is a rapidly progressive dementia often associated with malignancies, particularly those affecting the lung, breast, and testis.
• Prognosis: The prognosis is generally poor, as PLE is frequently linked to underlying cancers and may lead to rapid neurocognitive decline.

Limbic Structures Involved

• Hippocampus
• Amygdala
• Hypothalamus
• Insular and cingulate cortex

Aetiology

• Autoimmune Nature: PLE is an autoimmune disorder triggered by an immune response to cancer cells that cross-reacts with neurons in the limbic system.
• Associated Malignancies: Commonly associated with cancers such as small cell lung cancer, breast cancer, and testicular cancer.
• Diagnostic Autoantibodies: Specific autoantibodies (e.g., Anti-Hu, Anti-Ta, Anti-Ma) are frequently present and aid in diagnosis.
• Absence of Malignancy: In some cases, no underlying malignancy is identified despite clinical symptoms and antibody presence.

Clinical Features

• Neuropsychiatric Symptoms: Consider in patients with known malignancies presenting with delirium, confusion, or subacute memory impairment.
• Personality Changes: Subacute onset of personality alteration and severe amnesia.
• Seizures: Limbic-related seizures are common in PLE.
• Additional Brain Involvement: Brainstem and cerebellar involvement may lead to further neurological signs.
• Consciousness Alteration: Altered consciousness often accompanies seizures and may lead to episodes of unresponsiveness.
• Autonomic Dysfunction: Common symptoms include blood pressure instability, heart rate irregularities, and other autonomic disturbances.

Investigations

• Cerebrospinal Fluid (CSF): May show inflammatory changes, such as elevated white cell count or protein levels.
• MRI: Temporal lobe signal changes, often indicative of inflammation, are typically observed.
• Electroencephalogram (EEG): Slow waves, spikes, or slowing localized to the temporal lobe may be present.
• Autoantibody Testing: Specific antibodies, such as:
  • Anti-Hu (often associated with small cell lung cancer)
  • Anti-Ta (commonly linked to testicular cancer)
  • Anti-Ma (may appear in various cancers)
• Imaging for Malignancies: CXR, CT, or PET scans may be used to locate primary malignancies (e.g., small cell lung cancer).
• Additional Imaging: Testicular ultrasound, mammography, or other targeted imaging based on the suspected associated malignancy.

Management

• Treat Underlying Malignancy: Treatment of the associated cancer may improve neurological symptoms and help control the disease.
• Immunosuppressive Therapy:
  • Patients without identifiable malignancies may respond to immunosuppressive therapies.
  • High-dose corticosteroids are typically first-line treatment.
  • Other immunosuppressive agents, such as cyclophosphamide or intravenous immunoglobulins (IVIg), may be used in refractory cases.
• Supportive Care: Symptomatic management includes antiepileptics for seizures and interventions to stabilize autonomic functions.
• Prognosis: The outcome largely depends on early diagnosis and treatment, but overall prognosis remains guarded due to the underlying malignancy.

References

• Dalmau, J., & Rosenfeld, M. R. (2008). Paraneoplastic Syndromes Affecting the Nervous System. Clinical Neurology and Neurosurgery, 110(3), 227-233.
• Höftberger, R., & Rosenfeld, M. R. (2015). Antibody-Mediated Disorders of the CNS. Journal of Neuro-Oncology, 123(1), 87-99.
• Graus, F., & Dalmau, J. (2012). Paraneoplastic Neurological Syndromes: Pathogenesis and Treatment. The Lancet Neurology, 11(1), 1-9.
• National Institute of Neurological Disorders and Stroke. (2023). Paraneoplastic Limbic Encephalitis Information Page. Retrieved from NINDS Official Website