Received: 11 June 2021 Revised: 15 December 2021 Accepted: 27 January 2022 DOI: 10.1002/vrc2.310 CASE REPORT Wi l d l i fe Diagnosis and treatment of congenital hydrocephalus in a red fox (Vulpes vulpes) with seizures Marcos Raposo, Sònia Añor, Judit Verdés Vicente Soler Jaume Martorell, 1 Fundació Hospital Clínic Veterinari, Universitat Abstract Autònoma de Barcelona, Barcelona, Spain A 2-year-old male red fox (Vulpes vulpes) was presented for generalised tonic-clonic 2 Departament de Medicina i Cirugia Animals, seizures, blindness, compulsive circling and behavioural changes that occurred since the Facultat de Veterinària, Bellaterra (Cerdanyola del Vallès), Universitat Autònoma de Barcelona, animal was 2 months old. Neurological examination indicated a diffuse forebrain lesion. Barcelona, Spain On magnetic resonance imaging of the brain, a severe dilation of both lateral ventricles was identified. Congenital hydrocephalus was suspected and the fox was treated with Correspondence methylprednisolone, omeprazole and phenobarbital. Sixteen months later, the neuro- Sònia Añor, Fundació Hospital Clínic Veteri- nari, Universitat Autònoma de Barcelona, 08193, logical signs had improved: the frequency of seizures had decreased to one seizure every Barcelona, Spain. 3 months and compulsive circling was less pronounced. Email: sonia.anor@uab.cat K E YWOR D S MRI, red fox, seizures BACKGROUND subarachnoid space and disruption of the internal capsule adjacent to the caudate nucleus.4 Hydrocephalus can be divided into two major categories. In Congenital hydrocephalus can be treated medically with compensatory hydrocephalus, the increase in cerebrospinal drugs that decrease CSF production, such as furosemide, fluid (CSF) volume is secondary to loss of brain parenchyma acetazolamide, omeprazole and/or prednisone. Surgical treat- caused by a primary disease, such as in utero viral infections.1 ment consists of placement of a ventriculoperitoneal shunt Obstructive hydrocephalus is an increase in the volume of CSF (VPS).2 caused by obstruction of flow or decreased absorption of CSF. To the authors’ knowledge, congenital hydrocephalus diag- This can be due to a malformation (developmental obstruc- nosed by MRI and causing seizures has not been reported in tive hydrocephalus or congenital hydrocephalus), or it can be foxes. The purpose of this case report is to describe the neu- caused by acquired conditions that disrupt normal CSF flow, rological signs, MRI findings, treatment and outcome in a fox mainly inflammatory and neoplastic diseases.1 with congenital hydrocephalus. Congenital hydrocephalus is most commonly caused by stenosis of the mesencephalic aqueduct associated with fusion of the rostral colliculi. Other causes such as presence of CASE PRESENTATION immotile ependymal cilia or malformation of the arachnoid villi are less frequent.1 Clinical signs in dogs and cats are A 2-year-old male red fox (Vulpes vulpes) was presented for usually present at birth, although they might appear dur- generalised tonic-clonic seizures (GTCS) that lasted 1 minute ing the first months of life. The most common neurolog- and occurred every 10 days. The owner reported constant ical signs usually reflect forebrain dysfunction and include blindness and behavioural changes that included compulsive behavioural changes, blindness, circling, altered mental status circling. Clinical signs had been present since the animal was and seizures.2 2 months old, when it was rescued by the owners. Physical The gold standard for the diagnosis of hydrocephalus is examination was unremarkable, with normal head shape and magnetic resonance imaging (MRI).3 MRI findings allow dif- no open fontanelles palpable. ferentiating hydrocephalus from incidental ventriculomegaly. On neurological examination, the animal was obtunded, The main MRI findings include a ventricle/brain index >0.6, disoriented and walked in circles to the right side. Paresis elevation of the corpus callosum, dorsoventral flattening of was not observed, but postural reactions were delayed in the interthalamic adhesion, periventricular oedema, dilation all four limbs. Cranial nerve examination revealed absent of the olfactory recesses, thinning of the cortical sulci and/or vision and menace response bilaterally with normal pupillary This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2022 The Authors. Veterinary Record Case Reports published by John Wiley & Sons Ltd on behalf of British Veterinary Association Vet Rec Case Rep. 2022;e310. wileyonlinelibrary.com/journal/vrc2  of  https://doi.org/10.1002/vrc2.310  of  Veterinary Record Case Reports light reflexes, and absent response to stimulation of the nasal mucosa on both sides. A diffuse forebrain lesion was LEARNING POINTS/TAKE-HOME MESSAGES suspected, and the main differential diagnoses included anomaly, metabolic disease, cranioencephalic trauma (old) ∙ Congenital hydrocephalus should be considered as and inflammatory/infectious diseases. a differential diagnosis in young foxes with diffuse forebrain neurological signs. ∙ Medical management of congenital hydrocephalus INVESTIGATIONS with methylprednisolone and omeprazole was associated with clinical improvement in this case. Complete blood cell count (CBC) and serum biochemistry ∙ Despite lack of a therapeutic range for serum phe- showed a mild neutrophilic leukocytosis (white blood cell nobarbital concentration in foxes, in this case, a count 15.1 × 109 /L; reference range: 2.5 × 109 to 11.2 × 109 /L) good response to treatment with phenobarbital and segmented neutrophilia (14.2 × 109 /L; reference range: was achieved when serum phenobarbital concen- 0.55 × 109 to 7.31 × 109 /L), which were attributed to an tration reached therapeutic range for dogs. ulcerative dermatitis in the left forelimb. Serum biochemistry ∙ Pharmacokinetic studies to determine the serum showed elevated creatine kinase (CK 2851.2 UI/L; reference phenobarbital therapeutic range could be impor- range: 37–891 UI/L), which could be caused by the tonic- tant to manage epilepsy in foxes. clonic seizure suffered before hospital admission. Thoracic radiographs were performed to as a part of the preanaesthetic protocol to assess lung parenchyma and cardiac silhouette. Results were unremarkable. MRI was performed with a 0.4 T unit (Hitachi, Aperto TREATMENT Lucent). Dorsal, transverse and sagittal plane T2-weighted images (T2W; TR = 5832 ms, TE = 100 ms), transverse fluid- The fox was discharged on an anti-inflammatory dose of attenuated inversion recovery (T2-FLAIR; TR = 10,396 ms, methylprednisolone (Urbason 4 mg; Sanofi, Spain) (0.5 mg/kg TE = 90 ms, TI = 1800 ms) and transverse and sagittal PO every 24 hours), omeprazole (Omeprazol 10 mg; Nor- T1-weighted images (T1W; TR = 757 ms, TE = 13 ms) mon, Spain) (1 mg/kg PO every 24 hours) and phenobarbital before and after intravenous administration of para- (Luminaletas 15 mg; Kern Pharma, Spain) (2 mg/kg PO every magnetic contrast media (gadopentetate dimeglumine, 12 hours). On recheck examination 3 weeks after, the methyl- 0.1 mmol/kg bodyweight [Magnevist; Bayer, Spain]) were prednisolone dose was tapered (0.5 mg/kg PO every 48 hours) obtained. and omeprazole was stopped. On the 3-month recheck, the MRI revealed severe dilation of both lateral ventricles in methylprednisolone dose was recommended to be tapered to all the segments (rostral and temporal horns and central por- 0.25 mg/kg every 48 hours, but the owners refused to do it. On tions), absence of septum pellucidum, and irregular edges the 16-month recheck, the fox was on the same methylpred- and thinning of the cerebral cortex, as well as dilation of nisolone dose (0.5 mg/kg PO every 48 hours), phenobarbi- the left olfactory recess. The severe ventricular enlargement tal (5.6 mg/kg PO every 12 hours) and S-adenosylmethionine, caused elevation of the corpus callosum, bilateral disrup- silybin, vitamin E and selenium (Hepatosil 100/10; Phar- tion of the internal capsule between the lentiform and cau- madiet, Spain) (one tablet PO every 24 hours) were added date nuclei and dorsoventral flattening of the interthalamic because hepatic enzymes were increased on serum biochem- adhesion. In the left frontal lobe, there was a poorly defined istry (ALKP 267.7 UI/L; reference range: 20–156 UI/L; ALT lesion of finger-like appearance that communicated with the 302.2 UI/L; reference range: 39–102 UI/L). A bile acid assay left lateral ventricle. This lesion was isointense to CSF on was recommended, but the owners refused. T2W, hypointense on T1W and showed suppression of fluid signal on T2-FLAIR images. No contrast enhancement (CE) was observed on T1W images after contrast administration. OUTCOME AND FOLLOW-UP MRI findings were consistent with congenital hydrocephalus and a left frontal porencephaly (Figure 1). Analysis of the On recheck examination 3 weeks after discharge, the neuro- CSF collected from the cerebellomedullary cistern showed no logical signs had improved: mental status was alert and the abnormalities. compulsive circling was less pronounced. The absent postu- ral reactions, blindness, loss of bilateral menace response and absent response to stimulation of the nasal mucosa on both DIFFERENTIAL DIAGNOSIS sides remained unchanged for the 16-month follow-up period. The intensity of seizures also improved: the fox experienced Considering the young age of the fox and the nonprogressive only focal seizures (facial twitching) and no more GTCS. nature of the neurological signs, our main differential diag- However, the frequency of seizures was unchanged. Pheno- nosis was congenital hydrocephalus. Acquired hydrocephalus barbital serum concentration (9.1 mg/L) was below the nor- secondary to inflammatory or infectious diseases or neoplasm mal therapeutic range in dogs (15–40 mg/L), thus the pheno- was also considered. However, the nonprogressive course of barbital dosage was increased to 5.6 mg/kg PO every 12 hours. the signs and the unremarkable CSF analysis made inflamma- Phenobarbital serum concentration was then checked 3 weeks tory or infectious diseases unlikely. Neoplasia was excluded later and it had increased to 20.8 mg/L. Seizure frequency after MRI. had also decreased to one every month and the duration and Veterinary Record Case Reports  of  F I G U R E  Magnetic resonance images of the brain of the red fox (Vulpes vulpes). Midsagittal T2-weighted (a) image showing dorsoventral flattening of the interthalamic adhesion (arrow), dilation of the lateral ventricles and elevation of the corpus callosum. Dorsal T2-weighted (b) image showing a dilation of the left olfactory recess (asterisk). Transverse T2-weighted (c) image at the level of the caudate nucleus showing bilateral disruption of the internal capsule (plus). Dorsal T2-weighted (d) image showing dilation of the lateral ventricles and the left frontal porencephaly (white arrowhead) intensity of epileptic seizures were reduced. Sixteen months The main MRI findings such as dilation of the olfactory later, the animal remained stable, experiencing one focal recesses, elevation of the corpus callosum, disruption of the seizure every 3 months. Phenobarbital serum concentration internal capsule adjacent to the caudate nucleus and dorsoven- was 21.6 mg/L. The owners reported that the mental status and tral flattening of the interthalamic adhesion were indicative of behaviour had improved substantially after initiating treat- increased intraventricular pressure.4,8 The presence of poren- ment, and the compulsive circling has stopped at home. cephalic cavities in dogs with severe internal hydrocephalus was reported to be due to loss of parenchyma that was filled by CSF.9 DISCUSSION A standardised decision-making protocol for treatment of this condition does not exist in foxes. In dogs, there are two Congenital hydrocephalus is a relatively common disease in options: medical or surgical treatment. fox cubs abandoned by the vixen due to abnormal behaviour. Medical management with prednisone was chosen because In these animals, congenital hydrocephalus is suspected to it has been demonstrated to be effective in dogs.10 Omepra- be caused by infection with the Ljungan virus.5 A case of zole was also prescribed to reduce CSF production, although hydrocephalus associated with encephalitis diagnosed at post- its efficacy in dogs is controversial.11 Other drugs such as mortem examination was described in a fox by Mandara et al. acetazolamide combined with furosemide were not prescribed in 2007.6 In the case presented here, congenital hydrocephalus because of the side effects and lack of demonstrated efficacy.12 was suspected because of the nonprogressive course of clinical In the present case, an improvement was observed in men- signs, consistent MRI findings and normal CSF analysis. tal status and behaviour. The rest of the signs such as blind- Neurological deficits in dogs with hydrocephalus usually ness and proprioceptive deficits remained and were thought reflect a forebrain disorder and include abnormal behaviour, to be permanent chronic signs secondary to irreversible brain obtundation, blindness, circling and seizures,2 although the lesions. Prednisone should be tapered to the lowest possi- relationship between seizures and hydrocephalus has recently ble dosage that can control clinical signs or discontinued if been questioned.7 The fox presented here showed consistent possible.13 In this case, tapering was not performed because clinical signs. the owners refused to do so.  of  Veterinary Record Case Reports Surgical management of hydrocephalus by placing a ven- of findings in dogs with clinically relevant internal hydrocephalus and triculoperitoneal shunt is controversial. In the present case, asymptomatic dogs with ventriculomegaly. BMC Vet Res. 2015;11. https: //doi.org/10.1186/s12917-014-0312-6 it could have been indicated by the MRI findings,14 but the 5. Mullineaux E, Kebble E. Foxes. In: BSAVA manual of wildlife casualties. potential secondary complications described in dogs (shunt 2nd ed. Gloucester, UK: British Small Animal Veterinary Association; obstruction, shunt infection, pain and others),15 financial con- 2017. p. 260–74. cerns, plus the partial response to medical treatment and the 6. Mandara MT, Pavone S, Vitellozzi G. Internal hydrocephalus and presence of chronic signs did not support this option.2 associated periventricular encephalitis in a young fox. Vet Pathol. 2007;44(5):713–6. Anticonvulsant treatment with phenobarbital was also 7. Farke D, Kolecka M, Czerwik A, Wrzosek M, Schaub S, Kramer M, started. There was only one case described in a fox with et al. Prevalence of seizures in dogs and cats with idiopathic internal seizures caused by Lafora disease that was unsuccessfully hydrocephalus and seizure prevalence after implantation of a ventriculo- treated with phenobarbital.16 Phenobarbital serum concentra- peritoneal shunt. J Vet Intern Med. 2020;34(5):1986–92. tion was monitored despite lack of a therapeutic range in foxes. 8. Mai W. Congenital and developmental disorders. In: Diagnostic MRI in dogs and cats. Boca Raton, FL: CRC Press; 2018. p. 161–71. The therapeutic range for dogs was used as reference. Seizure 9. Mackillop E. Magnetic resonance imaging of intracranial malforma- intensity was reduced and the interictal period was prolonged tions in dogs and cats. Vet Radiol Ultrasound. 2011;52(1 Suppl 1):S42– when the phenobarbital serum concentration was within the 51. therapeutic range for dogs (15–40 mg/L).17 10. Gillespie S, Gilbert Z, De Decker S. Results of oral prednisolone adminis- tration or ventriculoperitoneal shunt placement in dogs with congenital hydrocephalus. J Am Vet Med Assoc. 2019;254(7):835–42. F U N D I N G I N F O R M AT I O N 11. Girod M, Allerton F, Gommeren K, Tutunaru AC, de Marchin J, Van The authors received no specific funding for this work. Soens I, et al. Evaluation of the effect of oral omeprazole on canine cere- brospinal fluid production: a pilot study. Vet J. 2016;209:119–24. CONFLICT OF INTEREST 12. Kolecka M, Ondreka N, Moritz A, Kramer M, Schmidt MJ. Effect of The authors declare that there is no conflict of interest that acetazolamide and subsequent ventriculo-peritoneal shunting on clini- cal signs and ventricular volumes in dogs with internal hydrocephalus. could be perceived as prejudicing the impartiality of the Acta Vet Scand. 2015;57(1):49. research reported. 13. Thomas WB. Hydrocephalus in dogs and cats. Vet Clin North Am Small Anim Pract. 2010;40(1):143–59. 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