Leptomeningeal Carcinomatosis from Gastric Adenocarcinoma: A Rare Culprit of Rapid Cognitive Decline in the Elderly

Abstract: A 72-year-old male presenting with acute confusion, subacute fatigue, and focal neurological symptoms was ultimately diagnosed with leptomeningeal carcinomatosis secondary to metastatic gastric adenocarcinoma. This case illustrates the necessity of a broad and evolving differential diagnosis for rapidly progressing neurocognitive decline in older adults, especially when initial findings are inconclusive. It also highlights the critical importance of meticulous diagnostic scrutiny of minor imaging abnormalities and cerebrospinal fluid (CSF) cytology.

Introduction Acute cognitive decline in elderly patients demands a rapid, yet comprehensive, diagnostic approach. Differential diagnoses span from infectious and metabolic etiologies to structural, neoplastic, autoimmune, and prion-related conditions. Leptomeningeal carcinomatosis (LMC), a rare and devastating manifestation of metastatic cancer, is seldom considered in initial evaluations, particularly when primary malignancy is occult. This article presents a case where subtle radiographic findings and iterative testing revealed gastric cancer-associated LMC, emphasizing clinical vigilance.

Case Presentation

History of Present Illness: A 72-year-old retired truck driver was admitted for acute confusion and agitation. One month prior, he experienced transient left leg weakness and persistent fatigue. His condition deteriorated rapidly, culminating in language disturbances and memory impairment. He had no history of fever, weight loss, or night sweats. He denied alcohol, tobacco, or drug use. Initial social and environmental exposures were non-contributory.

Initial Examination: Vital signs were stable. He was alert but disoriented, with impaired command following. Neurologic and systemic examinations were otherwise unremarkable.

Investigations: Routine labs, toxicology, and initial brain CT were non-diagnostic. Lumbar puncture revealed lymphocytic pleocytosis, elevated protein, and low glucose levels. Infectious and autoimmune panels were negative. Brain MRI showed symmetric enhancement of cranial nerves VII and VIII (Figure 1A) and ventriculomegaly without signs of obstructive hydrocephalus (Figure 1B). CSF 14-3-3 protein was elevated; however, hTau protein and prion imaging findings were absent. Autoimmune encephalitis panels and malignancy markers were negative.

[Figure 1A & 1B] A: Axial T1-weighted post-contrast MRI showing bilateral enhancement of cranial nerves VII and VIII (arrows). B: Axial FLAIR MRI revealing enlarged lateral ventricles suggestive of communicating hydrocephalus.

Clinical Deterioration and Revised Diagnostics: The patient’s cognitive and functional status deteriorated after discharge. Repeat admission showed severe dysphagia, mutism, and immobility. Further MRI and CT imaging of the chest, abdomen, and pelvis revealed subtle gastric wall thickening. Endoscopy with biopsy identified poorly differentiated gastric adenocarcinoma with signet-ring cells.

Repeat CSF cytology—collected via external ventricular drain—confirmed malignant cells consistent with leptomeningeal metastases. Earlier lumbar samples had been falsely negative.

Diagnosis: Leptomeningeal carcinomatosis was secondary to signet-ring cell gastric adenocarcinoma.

Discussion

1. Diagnostic Pitfalls in Rapid Cognitive Decline: When no obvious metabolic or infectious cause exists, clinicians must consider rare neuro-oncologic entities. Initial CSF cytology has a high false-negative rate. Minimum 10ml of CSF, rapid processing, and proximity to tumor sites improve diagnostic yield.

2. Neuroimaging Clues: Subtle enhancements of cranial nerves and unexplained ventriculomegaly should raise suspicion for CSF dissemination. In this case, the abnormal MRI findings preceded cytologic confirmation.

3. Paraneoplastic vs Direct Metastatic Processes: Initial considerations included autoimmune or paraneoplastic encephalitis. However, the absence of specific antibodies and pathognomonic imaging directed the focus toward direct metastatic involvement.

4. Rare Presentation of Gastric Cancer: Gastric cancer, particularly signet-ring variants, may metastasize to the leptomeninges even without gross systemic spread. This atypical dissemination pattern is associated with poor prognosis.

Management and Prognosis: Treatment options for LMC are largely palliative and include intrathecal chemotherapy and craniospinal radiotherapy. This patient’s cognitive function did not recover despite corticosteroids and immune therapies. LMC from gastric origin carries a dismal median survival of weeks to months.

Conclusion: This case underscores the importance of iterative diagnostics and maintaining a wide differential in cases of rapidly progressive cognitive decline. LMC, while rare, must be considered especially when subtle CNS imaging abnormalities coincide with persistent CSF pleocytosis. Gastrointestinal malignancies, although infrequent sources, should not be overlooked.

Quiz

1. What is the most important factor to increase the diagnostic yield of CSF cytology in suspected leptomeningeal carcinomatosis?

A) Repeated sampling and processing of large-volume CSF near disease sites

B) Using contrast-enhanced CT scan instead of MRI

C) Testing only once due to the risk of infection

D) Waiting until symptoms resolve before testing

2. Which MRI finding in this case suggested possible cerebrospinal fluid (CSF) pathway involvement by malignancy?

A) Enlarged ventricles and cranial nerve VII/VIII enhancement

B) Cerebellar atrophy

C) Normal gray-white differentiation

D) Acute hemorrhage in the basal ganglia

3. What malignancy was ultimately identified as the source of the leptomeningeal metastases?

A) Gastric adenocarcinoma with signet-ring cells

B) Non-small cell lung cancer

C) Primary CNS lymphoma

D) Prostate adenocarcinoma

Answer & Explanation

1. Answer: A) Repeated sampling and processing of large-volume CSF near disease sites.

Explanation: The diagnostic sensitivity of CSF cytology for detecting malignant cells in LMC increases significantly with the collection of large-volume CSF (>10 ml), repeat lumbar punctures or ventricular sampling, and immediate processing near the anatomical site of disease. A single test with low volume can result in a high false-negative rate, as occurred in the initial evaluation of this case.

2. Answer: A) Enlarged ventricles and cranial nerve VII/VIII enhancement

Explanation: MRI showing ventriculomegaly and symmetric enhancement of cranial nerves VII and VIII indicates abnormal CSF flow dynamics and nerve infiltration, which are classic indicators of leptomeningeal dissemination of malignancy. These findings, although subtle, preceded cytological confirmation of malignancy in this case.

3. Answer: A) Gastric adenocarcinoma with signet-ring cells

Explanation: Upper GI endoscopy and biopsy revealed a poorly differentiated gastric adenocarcinoma with signet-ring cells. This rare variant is known for its diffuse infiltration and potential to metastasize to the meninges, even without widespread systemic disease. It was confirmed as the origin of leptomeningeal carcinomatosis in this patient.

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