21 de ago de 2014

Sensory-Motor Neuropathy Due to Vincristine Treatment in a Dog


Acta Scientiae Veterinariae, 2014. 42(Suppl 1): 59.

Autores: Bernardo De Caro Martins, Guilherme De Caro Martins, Rodrigo dos Santos Horta, Bruno Benetti Junta Torres, Stephanie Elise Muniz Tavares Branco & Gleidice Eunice Lavalle
From: Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária (EV), Universidade Federal de Minas Gerais, Brazil

Background: Peripheral neuropathies secondary to chemotherapy drugs, especially when it comes to the use of vincristine, are common in humans, but rare in dogs. Neurologic manifestation depends on the kind of axonal fi bers involved. When motor fi bers are affected, weakness and ataxia are  observed. Sensory fibers involvement, which can lead to hyperesthesia, hypoesthesia or paresthesia was reported experimentally in rats, and is common in humans but were never reported in dogs. Thus, this report aims at describing a mixed neuropathy, with sensory and motor involvement, in a dog after vincristine treatment. 
Case: A one year old mixed breed dog, rescued from the street, was presented with multiple nodular and ulcerated lesions, disseminated on the head, gums, flank and limbs, with progressive worsening in the last two months. Cytology of two subcutaneous and one gum nodule revealed an intense concentration of neutrophils and round cells with abnormally clumped chromatin patterns, prominent nucleoli and multiple cytoplasmic vacuoles, compatible with TVT. Treatment was initiated with a weekly administration of vincristine (0,75 mg/m2) combined with anti-emetic (maropitant) and H1 receptor inhibitor (ranitidine). Fast remission of the cutaneous lesions occurred. However, after the second chemo session, generalized hyperesthesia, mild ataxia, intermittent collapse and vomiting were observed. Suspicion of a mixed (sensory-motor) neuropathy induced by vincristine emerged, and vincristine was ceased. No other chemotherapy treatment was instituted due to negative cytological results of the remaining lesions. Treatment with gabapentin (10 mg/kg, twice a day, orally) was initiated so that neuropathic pain was suppressed. After one week, the patient no longer demonstrated pain, walked normally and lesion remission was complete. The animal has been monitored for eight months and is currently stable, with no lesions, pain or any changes that compromises its quality of life.
Discussion: Although vincristine is considered to be the most effective and least toxic chemotherapy drug used for treating this neoplasia, some side effects may occur, such as vomiting, anorexia, depression and myelosuppression. In addition, some animals may suddenly develop peripheral neuropathy, with the involvement of motor fi bers, which results in weakness and ataxia. Involvement of sensory fi bers, in combination or not with motor fi bers, as vincristine treatment side effect, is commonly notice in humans but never observed in dogs, wherein allodynia and paresthesia can be manifested. In this case, the diagnosis of peripheral mix neuropathy, with motor and sensory fi bers involvement, was made by identifying clinical signs after vincristine treatment initiation and immediate remission after discontinuation. This is often enough for a defi nitive diagnosis, as there are no additional tests that identify, in an early matter, neuropathy caused by chemotherapy. Despite there is no specifi c treatment, gabapentin can be used to control neuropathic pain as it increases GABA and serotonin concentration, reducing nociceptive ascending impulses. After chemotherapy discontinuation and gabapentin treatment, there was remission of neurological signs. Vincristine-induced neuropathies constitute a persistent limitation of animal’s quality of life, especially when there is irreversible damage. It is important to identify early motor and sensory neurological signs so that chemotherapy can be immediately suspended. Therefore, the clinician must be able to identify the best moment to discontinue chemotherapy at the expense of patient’s clinical oncology state improvement, while prioritizing the animal’s quality of life.