Interventricular Brain tumor in a non descript dog - A case report

 

A 13-year-old non-descript neutered bitch, Rusty was presented with a complaint of intermittent circling, nocturnal anxiety, excitement, and head pressing for about 2 weeks. A complete blood count and biochemistry revealed no significant findings. The details of the complete physical and neurological examination are mentioned below

13 years

Vitals

Weight: 14.9 Kg

Heart Rate: 160

Capillary Refill Time: <2sec

Mucous Membrane: PINK

PHYSICAL EXAM

Comment: PET IS uncooperative and ferocious

PET IS excited, active, and minimally responsive), WELL-HYDRATED,-AMBULATORY

head: the calvarium of the skull is visibly enlarged and sensitive on palpation

chest: clear lung bilaterally

abdomen: tense on palpation, no abnormality detected 

integument: NSF

lymph node: NAD

Musculoskeletal: NAD

NEURO HISTORY: The owner noticed her dog walking in circles intermittently for about 2 weeks. She was able to have food and pass urine and stools normally till a day before the presentation the dog is restless and stands facing a corner of a room while pressing its head to the wall since yesterday. The owner also points out a vague history of the dog having a fall 3 months back which could have led to head trauma.

NEURO EXAM: Abnormal

MENTATION: Depressed/ obtunded but excited on arousal

BEHAVIOR: abnormal and  not cooperative with strangers

POSTURE: mild head turn to the right and a wide-based stance

GAIT - Ambulatory but short uncertain stride 

POSTURAL REACTION - The dog was not cooperative for detailed examination due to mania but all the below postural reactions apparently seemed normal.

Both Forelimbs paw placement

Both Pelvic limbs' paw placement  

Hopping forelimbs  

Hopping hindlimbs

Wheel borrowing  

CRANIAL NERVES: 

PLR - normal. Uncooperative for the remainder of cranial nerve examination 

THORACIC REFLEXES - Did not check.

PELVIC REFLEXES - Dog uncooperative

PERINEAL REFLEXES: 

Anal reflex - present 

WITHDRAWAL REFLEX: 3+ in all 4 limbs 

SUPERFCIAL/DEEP PAIN Perception : 3+ (hyperalgesia)

SPINAL PALPATION: Normal

CUTANEOUS TRUNCI REFLEX - 3+

Video recorded by the owners showing the compulsive circling behavior exhibited by the dog

SUMMARY

This is a chronic progressive condition with altered sensorium and generalized hyperalgesia. The findings of physical examination coupled with the history of circling and head pressing suggests that the lesion is present in the thalamocortical region of the brain

 

DIFFERENTIAL DIAGNOSIS

1. PRIMARY BRAIN TUMOR

2. SECONDARY BRAIN TUMOR

3. INFARCT OR THROMBUS IN THE BRAIN

RECOMMENDATIONS

ADVISED TO GET AN MRI DONE > CONSERVATIVE TREATMENT FOR NOW  

MRI FINDINGS - An Isointense mass with poor differentiation rostral to the cerebellum on a sagittal view T2-weighted image and a relatively hyperintense intraventricular mass noticed on a dorsal T2-weighted image. Significant contrast enhancement was observed after injecting Gadolinium as the contrast agent. All these findings suggest that the mass is most likely a choroid plexus tumor, if not a glioma. A Sagittal T1-weighted image revealed a severely dilated subarachnoid space containing the hypo-intense CSF which can be seen compressing the entire brain parenchyma.

       

Dorsal T2-weighted image without contrast showing the hyperintense CSF in the ventricles and the interventricular mass likely arising from the choroid plexus.

       

Dorsal T2-weighted image after injecting Gadolinium contrast showing the hyperintense interventricular mass likely arising from the choroid plexus.

        

Dorsal T1-weighted image post Gadolinium contrast showing the width of the mass

       

Sagittal T1-weighted image showing the relatively isointense mass rostral to the cerebellum

      

Sagittal T1-weighted image post Gadolinium contrast showing the hyperintense mass rostral to the cerebellum and the severely dilated subarachnoid space containing the hypointense CSF which can be seen compressing the entire brain parenchyma.

       

Sagittal T1-weighted image post Gadolinium contrast showing the measurements of the hyperintense mass rostral to the cerebellum

SUMMARY - Intraventricular mass most likely to be a Choroid plexus tumor or a Glioma. I came to the conclusion considering the location and radiographic characteristics of the mass. Only a histopathological study would confirm the origin of the tumor.

PROGNOSIS - GRAVE

Note - the dog experienced tonic-clonic seizures for the first time when sedated with Xylazine + Butorphanol before the MRI. Per-rectal Diazepam was administered to treat the same. Since a presumptive diagnosis of a brain tumor was made based on the radiographic findings and the likelihood of getting more such seizures in the future was high, anticonvulsive therapy was initiated. The dog survived for a week after which no updates were received from the owners.

PALLIATIVE TREATMENT  

Immunosuppressive dose of steroid (2.2 mg/kg prednisolone) +Phenobarbital 30 mg twice a day + Gabapentin @ 10 mg/kg twice a day

Note - The owners were advised to consider euthanasia as the animal was suffering badly. They were made to understand the root cause and the pain their dog was going through owing to the sharp raise in volume and pressure of CSF literally crushing the brain. Unfortunately, they opted out of it and resumed palliative treatment for about a week. The dog apparently showed mild signs of improvement and resumed taking feed orally the following day. This can be explained by the anti-inflammatory and diuretic action of the high-dose steroids administered.

Review of Literature

• Primary intracranial neoplasia in the dog represent about 2–5% of all cancers and is especially common in certain breeds including English and French bulldogs and Boxers. The most common types of primary intracranial cancer in the dog are meningioma, glioma, and choroid plexus tumors, generally occurring in middle-aged to older dogs.

• One article states that about 1 in every 6700 dogs gets a nervous system tumor in its lifetime, i.e.14.5 cases per 100,000 dogs.

• In dogs, about 90% of primary brain tumors (PBT) encountered in clinical practice are represented by 3 main tumors namely 

1. meningiomas (~50%), 

2. gliomas (~35%), and 

3. choroid plexus tumors (CPT; ~7%), 

Most PBT and SBT occur in middle-aged to older dogs, with the majority of cases described as being > 5 years of age. Median ages at diagnosis for dogs with gliomas, meningiomas, and CPT are 8 years, 10.5 years, and 5.5 years, respectively

• PBT are intracranial mass lesions that cause clinical signs of brain dysfunction by directly invading or compressing brain tissue and secondarily by causing peritumoral edema, neuroinflammation, obstructive hydrocephalus, and intracranial hemorrhage. Compensatory autoregulatory mechanisms, such as decreased cerebrospinal fluid (CSF) production and shifting of CSF into the spinal subarachnoid space, are effective at maintaining the intracranial pressure within physiologic ranges in the early phases of tumor growth.

However, with progressive increases in tumor volume, autoregulatory mechanisms are eventually overwhelmed and intracranial hypertension (ICH) develops. 

• Most PBT in dogs occur as solitary mass lesions, and tumors involving forebrain structures are more common than those in the brainstem 

• Cross-sectional diagnostic imaging techniques, such as computed tomography (CT) are the diagnostics of choice,  although MRI is the preferred modality for the assessment of animals with intracranial disease 

• Data obtained from MR imaging such as mass number (solitary vs. multiple), origin within the neuraxis (meningeal [extra-axial], parenchymal [intra-axial], or intraventricular), and intrinsic signal appearances, collectively provides characteristic patterns that allow for the presumptive diagnosis of most frequently encountered PBT and SBT in veterinary medicine or refinement of the list of differential diagnoses. 

• The accuracy of predicting the histological findings of the tumor type based on the diagnostic imaging features was found to be about 70% in one study. It remains common in veterinary practice to make clinical decisions in patients with presumptively diagnosed tumors based on imaging-derived data as surgical exploration, and incisional/excisional biopsy aren't always practically feasible with most general practices.

• Obtaining CSF in dogs with brain tumors and intracranial hypertension carries a risk of causing clinical deterioration and is contraindicated when a rise in intracranial pressure is expected. Exfoliated neoplastic cells may be observed in the CSF cytology of dogs with any type of brain tumor, but CPT, lymphoma, and histiocytic sarcoma are the tumors most commonly reported to be detected with CSF analysis

• While MRI is sensitive for the detection of intracranial neoplasms, a normal MRI does not rule out a brain tumor.

Diagnostic features of Glioma 

1. Intraparenchymal 

2. Irregular margins and poor differentiation. 

3. Peritumoral edema is not common.

4. Usually poor contrast enhancement. If  the tumor takes up the contrast, a “ring enhancing” pattern, in which a circular ring of contrast enhancement surrounds non-enhancing abnormal tissue, is often associated with gliomas  

5. Using conventional MRI sequences, it is not currently possible to reliably differentiate types of gliomas (astrocytomas from oligodendrogliomas) or accurately predict the grade of gliomas. However, contrast enhancement is more commonly observed in high-grade compared to low-grade gliomas

Diagnostic features of Meningioma 

1. Extra-parenchymal

2. Good contrast enhancement

3. Peritumoral edema is seen in 90% of cases

4. Histologically they are benign and slow growing

Diagnostic features of choroid plexus tumors 

1. Intraventricular location (Lateral and 4th ventricles)

2. Excellent contrast enhancement 

3. Secondary hydrocephalus is a common accompanying feature due to obstruction of the ventricular system.

Palliative care and Watchful Monitoring 

The goal of palliative care is to improve the quality of life of patients and their caregivers through the identification, assessment, and treatment of pain and other physical or behavioral manifestations of the brain tumor

1. Anticonvulsants - Phenobarbitone, Pragabalin, Levatiracetam

2. Corticosteroids - To target peritumoral edema and have a diuretic effect to relieve the excess CSF although surgical diversion is more efficient 

3. Polyuria, polydipsia, polyphagia, and sedation are commonly anticipated and reported adverse effects of palliative treatment, but palliative therapies are rarely associated with significant morbidity that necessitates discontinuation of therapy

4. Analgesia - pain can arise from compression or stretching of the meninges, nerve roots, or vasculature, tumor-associated meningitis, neuritis, or radiculitis, and tumor infiltration of the periosteum or musculature.  Clinical signs consistent with pain often respond to corticosteroid treatment, and additional narcotic or neuropathic pain agents can be added as indicated. 

When data for all PBT is pooled, the median survival time (MST) following palliative care is ~9 weeks, with a range of 1–13 weeks 

Chemotherapy 

1. Significantly limited data because of lack of definitive tumor diagnosis

2. The most commonly used chemotherapeutics for brain tumors are the alkylating agents- Lomustine (CCNU), Carmustine (BCNU), and Temozolomide (TMZ), or the antimetabolite hydroxyurea, all of which penetrate the blood-brain-barrier (BBB)

3. One retrospective study in 71 dogs with presumptively diagnosed brain tumors reported that Lomustine treated dogs experienced no survival benefit compared to dogs receiving palliative therapy 

4. In another study conducted in dogs with intra-axial mass lesions (presumptively diagnosed gliomas), dogs treated with Lomustine survived significantly longer than dogs receiving palliative care only. In general, the prognosis is poor for dogs with PBT treated with chemotherapy when used as a monotherapy in the setting of gross disease. 

Surgery 

Surgical treatment of brain tumors is infrequently attempted as approaching and removing them is technically demanding especially if they are located intra-axial or intraventricular locations. Also, the insignificant survival times and quality of life following the surgery are factors to opt out of surgery. In addition, as these tumors are poorly delineated and locally invasive, it is inherently more difficult to discriminate the margins of the tumor from the neighboring neural tissue.

Radiation therapy 

RT is beneficial for the treatment of PBT when used as a monotherapy or adjunctive modality but studies relating to the efficacy of radiation therapy on specific tumor types are lacking in the veterinary literature. 

References and Further Reading 

1. Miller, A. D., Miller, C. R., & Rossmeisl, J. H. (2019). Canine Primary Intracranial Cancer: A Clinicopathologic and Comparative Review of Glioma, Meningioma, and Choroid Plexus Tumors. Frontiers in oncology, 9, 1151. https://doi.org/10.3389/fonc.2019.01151

2. Rossmeisl JH, Pancotto TE. Intracranial neoplasia and secondary pathological effects. In: Platt S, Garosi L, editors. Small Animal Neurological Emergencies. London: Manson Publishing Ltd; (2012). p. 461–78. 10.1201/b15214-30

3. Rodenas S, Pumarola M, Gaitero L, Zamora A, Anor S. Magnetic resonance imaging findings in 40 dogs with histologically confirmed intracranial tumours. Vet J. (2011) 187:85–91. 10.1016/j.tvjl.2009.10.011 

4. Moirano SJ, Dewey CW, Wright KZ, Cohen PW. Survival times in dogs with presumptive intracranial gliomas treated with oral lomustine: a comparative retrospective study (2008-2017). Vet Comp Oncol. (2018) 16:459–66. 10.1111/vco.12401

5. Practical Guide to Canine and Feline Neurology by Curtis W Dewey and Ronaldo C da costa.

6. Handbook of Veterinary Neurology by Michael D Lorenz, Joan R Coates and Mark Kent