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CASE REPORTS
Subacute dementia as presenting feature of carcinomatous leptomeningeal metastases María Sereno Moyano, Enrique Casado Saenz, Cristóbal Belda Iniesta and Manuel González Barón Servicio de Oncología Médica. Hospital de La Paz. Madrid. Spain.
Demencia subaguda como cuadro de presentación de carcinomatosis meníngea La carcinomatosis leptomeníngea constituye una seria complicación de los tumores sólidos y hematológicos extraneurales y ocasional en las neoplasias primarias del sistema nervioso y que cuenta con una mediana de supervivencia inferior a 6 meses. El cáncer de mama, pulmón y gástrico así como el melanoma, el linfoma y la leucemia son las neoplasias más comunes implicadas en la invasión leptomeníngea. Esta complicación se presenta con síntomas y signos sugestivos de alteración de pares craneales. El líquido cefalorraquídeo (LCR) normalmente presenta pleocitosis, aumento de las proteínas e hipoglucorraquia. Los hallazgos típicos de la resonancia magnética nuclear consisten en incrementos focales de la captación de gadolinio. Finalmente el diagnóstico se confirma mediante el examen patológico del LCR. Se han desarrollado diversas estrategias de radioterapia y quimioterapia, sin embargo, pese a estas intervenciones la mayoria de los pacientes fallecen dentro de los 6 meses del diagnóstico siendo la mediana de supervivencia en estudios recientes de 6 a 16 semanas. Palabras clave: carcinomatosis leptomeníngea, demencia subaguda. Sereno Moyano M, Casado Saenz E, Belda Iniesta C, González Barón M. Subacute dementia as presenting feature of carcinomatous leptomeningeal metastases. Clin Transl Oncol. 2005;7(1): 29-30.
CASE REPORT We report a case of a 77 years old woman with a history of hypertension and histerectomy with double ooforectomy for a bening ovarian tumor two years ago. During the last two months she had developed a progressive deterioration of the memory for recent events with apraxia and disorientation. Also, she became
Correspondence: María Sereno Moyano. Paseo del Carraperal, 33. Griñón 28940 Madrid. España. E-mail:
[email protected]
DISCUSSION
Received 2 December 2003; Revised 15 April 2004; Accepted 28 April 2004. 53
unable to manage for basic activities. Previously to admission, she started with headache, nausea and vomits. Her physical examination showed poor memory, flat affect and incongrous animo. Neurologic examination didn´t reveal other abnormalities. Her blood test and cultures were rigorously normal with the exception of carcinoembrionary antigen (CEA) and Ca 15.3 levels (144.2 and 40.6). Neurospecific enolase, α-FP and Ca 125 were normal. Thyroid hormones levels were within normal limits and B12 levels. Serologic studies for citomegalovirus (CMV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), borrelia, syphilis and M. pneumoniae obtained negative results. Psychiatric exams did not show functional diseases as depression, anxiety or psichosis. Contrast-enhanced computed tomography of the head revealed a very dilated ventricular system, with temporal and front horns alterations. There was a low density around front horn suggesting a mild transependymal trasudation of CSF. Cortical grooves were scarce for her age. In addition, a number of contrastenhanced images arising from the bone inner surfacehinting a leptomeningeal origin-were found. Magnetic resonance imaging (MRI) showed a diffuse enhanced meningeal gadolinium uptake. CSF analysis was consistent with leptomeningeal invasion: hypoglycorrhachia 0.36 g/l (0.45-0.8), pleocytosis (WBC count of 20 /mm3) and increased protein levels (454 ηg/l 160-400). Immunoglobulins, albumina and their ratio were normal. CSF β2-microglobulin was augmented (1,711 ηg/l , normal 750-1,150) but this parameter was normal in plasma, so the CSF/plasma ratio resulted high. Cytology yielded large malignant and pleomorphic cells with enlarged nuclei, occasional nucleoli, and coarse chromatin, all these findings suggestive of meningeal metastases. Body-scan disclosed an isolated 1.5 cm- 2 cm node in the posterior segment of the right upper lobe with a atelectasia. Enlarged mediastinal lymph nodes were not found. At this time, paliative CNS irradiation were administered. Some days later, patient was moved to a Paliative Care Hospital were she had a respiratory sepsis. She did not response to intense antibiotherapy and died 15 days later.
The most common originating sites of tumors producing carcinomatous meningitis are breast and lung1-5. It is estimated that 1%-3.5% of patients with metasta-
Clin Transl Oncol. 2005;7(1):29-30
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Document downloaded from http://www.elsevier.es, day 24/04/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
SERENO MOYANO M, CASADO SAENZ E, BELDA INIESTA C, ET AL. SUBACUTE DEMENTIA AS PRESENTING FEATURE OF CARCINOMATOUS LEPTOMENINGEAL METASTASES
tic breast cancer experience carcinomatous meningitis in the absence of parenchymal brain disease and in 6% of patients with secondary central nervous system involvement. It has been reported that, two thirds of the patients with carcinomatous meningitis have features of lobular histologic type in their primary tumors2. Patients with carcinomatous leptomeningeal metastases usually develop multiple cranial neuropathies, patchy radiculopathies or mental status changes. The most frequent presenting findings are meningeal irritation (mainly headache) and cranial nerves palsies affecting to the extraocular muscles. Also multiplex mononeuritis, raised intracranial pressure, cerebellar dysfunction, epilepsy, lower motor neuron spinal nerve lesions, confusion and cortical dysfunction are common3. Dementia seems to be a rather unusual presenting sympthom and to our knowledge, no other cases have been published before. Our first differential diagnoses to be ruled out was Alzheimer´s dementia. The patient met all criteria for this disease: memory deterioration, disphasia, apraxia and impairment in cognitive and social abilities without oscilation in the level of conciousness. However the diagnosis of Alzheimer disease can only be established if other organic causes of dementia have been previosly excluded. Anoter dementia causes were infectious: Creuzfeld-Jacob disease, syphilis, HIV infection, virous meningoencephalitis; metabolic causes: alcohol, tyrhoid disease, drugs intake and B12 vitamin deficit; vascular dementia secundary to cronic ischemic accident or Bisswanger disease was excluded, too. Sometimes, psychiatric pathology as depression, cronic anxiety or psycosis has similar evolution, but these causes were exclude in a complete psycopathologic exam. Another intracranial process to consider were brain tumors with a slow growth as meningioma or low grade glioma; this was not the case, as computed tomography (CT) showed the aformentioned abnormalities. We can conclude that our patient suffered dementia due to an hydrocefalous caused by multiple leptomeningeal metastasis. The pathogenic mechanism that can trigger this complication include tumor aggregates compressing penetrating arteries in the Virchow-Robin spaces of the brain, nerve root compressions or obstructive hydrocephalus resulting in blockage of CSF flow2. It is convenient to consider leptomeningeal metastasis always ocurs after a long time from cancer diagnosis. In our patient this phenomenon appears as debut of this pathology, feature very exceptional. The gold standard for diagnosing this disease is still cytologic confirmation of malignant cells in the CSF. Gd-MR does not replace the need for cytologic examination of CSF. Although CSF cytology turns out to be positive in only 54% of the initial spinal taps, CSF protein levels are elevated in 81% of the cases; with a second tap, the cumulative positive rate of CSF cytology
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increases to 91%4. Also abnormal CSF flow is common in patients with leptomeningeal cancer. Several groups have documented normal ventricular CSF kinetics using radionucleid ventriculography with Iridium 1115 and Technetium-99m-DTPA1. These abnormalities in the cerebrospinal flow are associated with poor terapeutic responses to intrathecal chemotherapy due to restricted access of the drug to the tumor, and with treatment-related toxicity derived from high local drug concentrations. Once the subaracnoid space is infiltrated by tumor cells, widespread involvement of the leptomeninges ensues. Consequently, intrathecal chemotherapy is the mainstay of treatment. Notwithstanding systemic drugs may occasionally also be beneficial5. Radiotherapy is usually reserved for areas of bulk or symptomatic leptomeningeal disease6. The prefered route for delivery of intrathecal chemotherapy is through an Omaya reservoir. There are some drugs used for this porpose as methotrexate, thiotepa, cytarabine and sustained-release cytarabine1,7. In summary, the treatment of meningitis carcinomatous is not curative and patient survival is usually less than 6 months. Radiation therapy and intrathecal chemotherapy can offer palliation by arresting neurologic progression in clinically stable patients. Some authors suggest that patients with a poor performance status (KP
