Colorectal Cancer Presenting with Initial Neuropsychiatric Symp- toms Due to Brain Metastases

Metastatic involvement of the brain from Colorectal Cancer (CRC) is rare and confers a poor prognosis. Up to 6% of all patients with CRC develop brain metastasis, thus necessitating surgical resection or radiation therapy. We report a case of an 80-year-old male, who presented to us with progressively worsening cognitive function that was initially suggestive of a primary neuropsychiatric disorder. Magnetic Resonance Imaging (MRI) brain revealed multiple ring-enhancing lesions in the brain that were concerning for metastatic tumor spread. In light of mild elevation of liver enzymes, Computerized Tomography (CT) scan of the abdomen was performed that showed multiple hepatic and skeletal metastases. Subsequent colonoscopy confirmed left adenocarcinoma of descending colon as the primary site of tumor origin.


Introduction
Colorectal Cancer (CRC) is the third most common malignancy in the world after lung and breast cancer with an incidence of 1,361,000 cases in 2012 [1]. It is responsible for around 51,000 deaths in the US due to this cancer in year 2010 [2]. If detected early, most cases involve surgical resection of the tumor site, even if metastasis are noted with liver. Metastasis of CRC to the brain is a rare entity [3]. It is estimated that CRC metastasizes to the brain in approximately 0.3% -6% of cases [4]. It is very rare for CRC to present with neuropsychiatric manifestations as a result of intracranial spread. We report a case of colonic adenocarcinoma that presented with progressive cognitive decline as its initial clinical manifestation.

Case Report
An 80-year old male presented to the Emergency Department (ED) with a two-day history of worsening confusion in the background of progressively deteriorating cognitive and behavioral disturbances for last three months. His past medical history was only remarkable for hypertension. The patient's family had noted irritability in his behavior over the last few months. He would utter profanities over minor issues at home with an increasing tendency towards aggression. In the last month, the patient had attempted suicide by overdosing of diclofenac potassium, however he was successfully resuscitated at his local health clinic. Initial neurologic evaluation in the ER showed incoherent speech and confusion. He was disoriented in terms of time, place and person. Initial Glasgow Coma Scale (GCS) was eight out of fifteen (E2, M5, V1). The patient was afebrile (99°F) and blood pressure was 170/110mmHg. DOI: 10.29011/JSUR-164.000064 His exam did not reveal any focal neurological deficit. Initial blood laboratory results showed: Hemoglobin 11.4 (13-17 g/dl); white cell count, 11.3 (5-11 X 109 cells/litre); serum creatinine, 2.1 mg/dl (0.7-1.5 mg/dl); serum potassium, 5.3 (3.5-5.0 mmol/l); serum sodium, 125 mmol/l (135-145 mmol/l). He was rehydrated with intravenous fluids that led to improvement in renal function and electrolytes. Computerized Tomography (CT) scan of the brain showed a hypodense lesion on the left side of the brain (red arrow in (Figure 1 (a)). Lumbar puncture was done and Cerebrospinal Fluid (CSF) specimen sent for complete analysis (unsure if we should include this). Empiric antibiotic therapy was then started with intravenous ceftriaxone and vancomycin. This prompted the need for Magnetic Resonance Imaging (MRI) of the brain, that demonstrated multiple ring enhancing lesions with associated cerebral edema ( Figure 1(b-e)).

Figure 1(a-e):
Axial section of brain of an 80-yrs-old male with metastasized Colorectal Cancer. (a) CT brain without contrast shows a rings-like focal lesion (arrow) in the left frontal lobe with cerebral edema. (b) MRI brain (post-contrast) shows ring enhancing lesions in the left frontal lobe with cerebral edema. (c) MRI brain (post-contrast) T1 weighted image shows ring enhancing lesion in the left temporal lobe (arrow). (d) MRI brain (post-contrast) T1 weighted image shows ring enhancing lesion on the left side of brain. (e) MRI brain (post-contrast) T2 weighted image shows hyperintense lesion (arrow).
These findings were concerning for toxoplasmosis, Acquired Immune Deficiency Syndrome (AIDS), lymphoma or metastatic disease. CSF testing did not reveal any atypical cells. (Table 1).

CSF Analysis
Color Colorless  The patient showed initial clinical improvement with dehydration, however in the next few days, he developed gradual abdominal distension and constipation. Digital rectal examination showed empty rectum with normal anal sphincter tone. Sonographic Scan (USG) of the abdomen showed dilated gut loops along with a focal lesion in the liver. Several viral, parasitic and tumor markers were done for this suspicious liver mass (Table 2).

Viral Markers
Anti-HCV titres Negative  Carcinoembryonic Antigen (CEA) levels were found to be significantly high, raising the suspicion of malignancy. CT scan of abdomen and pelvis was done that revealed marked distension of colon along with skeletal and liver metastases (Figure 2 (a-c)). Colonoscopy confirmed the in left descending colon. Proctosigmoidectomy with end colostomy (Hartmann's procedure) was planned by the surgical team as a palliative procedure. The attendants were counseled regarding patient's critical condition and the risks associated with surgery. On the tenth day of admission, the patient's condition started to deteriorate as his blood pressures continue to drop. Surgery was postponed. Supportive therapy was initiated with vasopressors and supplemental oxygen. Eleven days after his admission, the patient suddenly collapsed and died.

Discussion
Our case has fugue state which is not very commonly reported in metastatic disease, although theoretically, it is possible. The disease course was peculiar and rapid that engulfed the vascular as well as the neurological homeostasis. In Pakistan, there is no set protocol or recommendation for the colonoscopy, increasing the rate of late diagnosis. The best way to catch CRC in early stages is to have a detailed family directory of previous positive cases in a family, following standardized screening protocol of colonoscopy and avoiding the known etiologies including a healthy fiber diet. The prognosis is not very satisfactory and depends on various factors involving age, performance status and site of the primary tumor. The predictors of survival in this condition are less discussed in the literature. Though it is notable to discuss that even though after rigorous treatment plan and compromised lifestyle the median survival is not more than 3 to 6 months [5,6]. This brings in account the clinician's decision and caregivers to decide for a difficult treatment that compromises lifestyle versus palliative care. Most of the brain metastases have the primary tumor at distal colon or rectum and least common in the proximal colon. This is also suggested by studies that metastasizing to the brain is the probably the last course of the disease and multi-organ metastasis is already known by then [5]. A study suggested that the reported median age of brain metastasis patients was 63 years with grade 2. The median time duration from diagnosis of CRC to the brain was 29.2 months. Usually, uni-focal lesion of metastasis was found and as mentioned earlier this study also documented a less survival rate once it was found in the brain [7]. Another study brought in account that the median age of diagnosis of brain metastases of CRC was around 66 years and proposed that this condition is the late-stage phenomenon which is less promising in prognosis irrespective of sex, performance status, and early treatment modality [8]. The chances of survival are diminished and quality of life compromised in the gastrointestinal tumors metastasizing to the brain, unlike its presentation and treatment when involving breast, lungs or liver [9].

Conclusion
Metastasis to the brain is a very difficult disease for both, clinician and the patient. For the clinician, it is challenging in deciding the appropriate treatment plan as well as handling the social norms of expressing the survival of the patient. Also, it is important that once the CRC is diagnosed, the possibility of lesions in other sites of the body should be considered and appropriate management plan should be devised early in time. All the factors that contribute in CRC should be known to the general public to minimize the primary lesion at the first place.