Veterinary Ophthalmology - 2017 - Hamzianpour - Clinical signs imaging findings and outcome in twelve cats with internal.pdf

Veterinary Ophthalmology (2018) 21, 4, 382–390 DOI:10.1111/vop.12523 Clinical signs, imaging findings, and outcome in twelve cats with internal ophthalmoparesis/ophthalmoplegia Negar Hamzianpour, Richard Lam, Roser Tetas and Elsa Beltran Department of Clinical Science and Services, Royal Veterinary...

Veterinary Ophthalmology (2018) 21, 4, 382–390 DOI:10.1111/vop.12523 Clinical signs, imaging findings, and outcome in twelve cats with internal ophthalmoparesis/ophthalmoplegia Negar Hamzianpour, Richard Lam, Roser Tetas and Elsa Beltran Department of Clinical Science and Services, Royal Veterinary College, University of London, Hawkshead Lane, North Mymms AL9 7TA, Hatfield, UK Address communications to: E. Beltran Tel: +44 (0)1707 666365 Fax: 01707 649 384 e-mail: [email protected] Abstract Objective To retrospectively evaluate the clinical signs, imaging findings, and outcome of feline internal ophthalmoparesis/ophthalmoplegia. Procedure Medical records were reviewed from 2008 to 2015. Inclusion criteria included cats that presented with internal ophthalmoparesis/ophthalmoplegia, underwent diagnostic imaging, and had follow-up information available. Results Twelve cases of feline internal ophthalmoparesis/ophthalmoplegia were identified. Nine cats were unilaterally affected, and three cats were bilaterally affected. Affected cats had a median age of 10.54 years (range 5.75 to 13.17), and both sexes of varying breeds were affected (nine males; three females). Clinical signs including abnormal mental status (n = 9; 75%) and additional neurologic abnormalities (n = 10; 83%) were observed. Magnetic resonance imaging and/or computed tomography (MRI/CT) of the head were performed in ten cats, revealing a mass lesion in all cases with varying locations. Multicentric lymphoma was diagnosed in two cats via abdominal ultrasound and cytology. All twelve cats were euthanized due to deterioration of clinical signs and/or quality-of-life concerns. Median time from diagnosis to euthanasia was 3.5 days (range 0 to 80 days). Conclusions Feline internal ophthalmoparesis/ophthalmoplegia rarely presents as the sole clinical sign in a referral hospital. Advanced imaging (MRI/CT) may be necessary to reach a definitive diagnosis in these cases. However, abdominal ultrasound would be advocated in cats with systemic clinical signs as a less expensive and less invasive diagnostic test to further investigate the possible etiology of internal ophthalmoparesis/ophthalmoplegia prior to advanced imaging. Feline cases with internal ophthalmoparesis/ophthalmoplegia associated with other intracranial signs and/or systemic clinical signs have a poor prognosis. Key Words: feline, imaging, internal ophthalmoplegia, neuro-ophthalmology, oculomotor, parasympathetic INTRODUCTION Internal ophthalmoparesis/ophthalmoplegia is characterized by decreased (ophthalmoparesis) or absent (ophthalmoplegia) motor function of the iris sphincter and ciliary body muscle. This is due to loss of parasympathetic innervation from the oculomotor nerve [cranial nerve (CN) III], observed clinically as areflexive mydriasis.1 Documented cases of feline and canine internal ophthalmoparesis/ophthalmoplegia are limited in the veterinary literature. Most of the literature in dogs and cats with internal ophthalmoparesis/ophthalmoplegia are case reports with middle cranial fossa syndrome (also known as cavernous sinus syndrome).2–11 Middle cranial fossa syndrome is a clinical disorder characterized by ipsilateral internal ophthalmoparesis/ophthalmoplegia, paresis, or plegia of the extra-ocular muscles (also known as external ophthalmoparesis/ophthalmoplegia) and decreased to absent facial and corneal sensation.12,13 These clinical signs are due to a dysfunction of several cranial nerves that course at the level of the middle cranial fossa.12,13 These cranial nerves include CN III (motor and parasympathetic component), CN IV (trochlear nerve), CN VI (abducens nerve), the ophthalmic branch of the CN V (trigeminal nerve), and postganglionic sympathetic nerve fibers. The maxillary branch of the CN V, which passes through the round foramen, can also be affected. This is usually due to an intracranial mass or retrobulbar mass invading the orbital fissure or the middle © 2017 American College of Veterinary Ophthalmologists cranial fossa. Case reports in dogs have included chondrosarcoma, lymphoma, meningioma, primitive neuroectodermal tumors, metastatic invasion of thyroid carcinomas, neuroendocrine carcinoma, and an aneurysm as the underlying cause.2–7 Reports in cats have included osteochondroma, lymphoma, squamous cell carcinoma, chondrosarcoma, trauma, orbital abscessation, and infectious diseases (feline infectious peritonitis/Cryptococcus) as the underlying cause.7–11 Lesions affecting the CN III alone and causing internal ophthalmoparesis/ophthalmoplegia as the sole clinical signs are more rarely reported. Dysautonomia and pharmacological blockage with mydriatic agents, such as atropine, in both dogs and cats, have to be considered.14–17 In dogs, it has been reported in the literature secondary to intracranial meningiomas, intracranial suprasellar germ cell tumors, toxic contact (e.g., to Datura stramonium), or as an idiopathic cause.18–25 Feline reports in the literature are confined to metastasis of a renal cell carcinoma, thiamine deficiency, viruses (e.g., feline leukemia virus), and as an idiopathic cause, all of which should be considered in our feline patients.26–29 Internal ophthalmoparesis/ophthalmoplegia is more commonly reported in the human literature. It has been reported secondary to a diabetic neuropathy, autoimmune disease, ophthalmoplegic migraine, trauma, cavernous sinus thrombosis, and compressive lesions such as intracranial aneurysms and space-occupying lesions.30–38 The aims of this study were to describe the clinical features, imaging findings, and outcome of feline cases presented with internal ophthalmoparesis/ophthalmoplegia. MATERIALS AND METHODS Medical records from the Royal Veterinary College’s Queen Mother Hospital were reviewed from 2008 to 2015. Inclusion criteria were as follows: cats that (i) presented with internal ophthalmoparesis/ophthalmoplegia; (ii) had complete medical records (including ophthalmic and neurologic examinations performed by a board-certified ophthalmologist and neurologist, respectively); (iii) underwent diagnostic imaging; and (iv) had follow-up information available. Ophthalmic examination must have included a neuroophthalmic examination (menace response, palpebral reflex, corneal reflex, dazzle reflex, direct and consensual pupillary light reflex (PLR)), Schirmer tear testing, examination of facial symmetry, a complete slit-lamp examination, indirect funduscopy, and rebound tonometry. Neurologic examinations must have included assessment of mental status, gait, posture, cranial nerves, postural reactions, spinal reflexes, and areas of possible hyperesthesia. The criteria for the clinical diagnosis of internal ophthalmoparesis were a mydriatic eye with a decrease in the direct PLR, a decreased consensual PLR (from the contralateral eye to the affected side), and intact vision. Internal ophthalmoplegia was considered when the direct and consensual PLR were absent in a mydriatic eye, but the vision was intact. Vision was assessed primarily by the menace response. However, in some cats, other means of testing, including a cotton ball test and navigation around the room, were used if the menace response was decreased to absent. Iris atrophy, iris hypoplasia, glaucoma, posterior synechia, and other causes of iris muscular dysfunction had to be ruled out for the case to be included. Data retrieved from the medical records included signalment, history, physical, ophthalmic and neurologic examinations at presentation, imaging findings, ancillary diagnostic tests, cerebrospinal fluid analysis when available, treatment, and outcome/follow-up. Postmortem findings were recorded if available. Magnetic resonance imaging and CT findings were reviewed independently by a board-certified neurologist (EB) and a board-certified radiologist (RL). The images were described for each case. Ultrasound and radiographic findings were also reviewed when available (RL). Short-term outcome was defined as survival or nonsurvival 48 h after diagnosis. The long-term outcome was assessed, when available, at 1, 2, and 3 months after diagnosis. Follow-up information was obtained by telephone consultation with the owner and/or the referring veterinarian and combined with information from the medical records, including any gross pathology and histopathology reports. RESULTS Internal ophthalmoparesis/ophthalmoplegia was identified in twelve cats. The cats had a mean age of 10.33 years and a median age of 10.54 years (range 5.75 to 13.17). Breeds affected were eight Domestic Short-hair cats and one of each of the following: Domestic Long-hair, Tonkinese, British Short-hair, and Burmese cat. Nine cats were male (neutered n = 9, 75%), and three cats were female (spayed n = 2, 17%, or intact n = 1, 8%). The results of the physical, ophthalmologic, and neurologic examinations are summarized in Table 1. Unilateral internal ophthalmoparesis (right eye only (OD) n = 1, 0.08%) (Fig. 1) or ophthalmoplegia {(total n = 8, 67%), OD = 4, 33%, left eye (OS) = 4, 33%} was present in nine cats (75%). One cat (case 4) presented with unilateral internal ophthalmoparesis (OD); however, this progressed to bilateral internal ophthalmoplegia 14 days following initial presentation. Bilateral internal ophthalmoparesis was present in one cat (case 10) at presentation. Case 11 had internal ophthalmoparesis OD and internal ophthalmoplegia OS. The neurologic examination at presentation revealed the following: obtunded mental status (n = 9, 75%), abnormal behavior (circling n = 3, 25%; pacing n = 1, 8%; compulsive behavior n = 1, 8%), proprioceptive ataxia © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License feline internal ophthalmoplegia 383 DSH 6.75 MN Burm. 9.41 FE DSH 13.17 FN DSH 11.08 MN Case 1 2 3 4 BSH 12.25 MN Tonk. 5.75 MN DSH 11.34 MN DSH 15.00 FN DSH 10.00 MN DLH 8.75 MN DSH 7.50 MN 6 7 8 9 10 11 12 OU OU 21 30 OD OD 3 Unknown OD OS OS 30 2 10 OD OU 17 2 OD OS OD OS Side of mydriasis 3 21 7 5 Duration of mydriasis (d) Paresis OS: plegia OD: paresis Plegia Plegia Plegia Plegia Plegia Plegia Plegia Paresis Plegia Plegia Plegia Parasympathetic component CN III NA Paresis NA NA NA Plegia NA NA NA NA Plegia NA Plegia Motor component CN III None None OS: enophthalmus None OU: scleral vessel congestion, edematous optic disks with areas of retinal detachment OU: 3rd eyelid protrusion OS: exophthalmus None OD: corneal ulcer OS: focal white iridal mass OS: diffuse corneal opacity OU: aqueous flare, uveitis, and iridal hemorrhages None None None Other ophthalmic signs Obtunded Seizures Proprioceptive ataxia Ambulatory tetraparesis Positional vertical nystagmus OD: menace response, absent palpebral reflex (CN V), ↓ corneal reflex (V) Obtunded Circling to the R L PL and TL postural reaction deficits Obtunded Proprioceptive ataxia Compulsive behavior Obtunded Circling to the R ↓ L PL and TL postural reaction deficits Cervical hyperesthesia Obtunded Circling to the R Proprioceptive ataxia ↓ R-sided postural reaction deficits OD: ↓ menace response, ↓ palpebral reflex (VII) Obtunded Obtunded OU: absent menace OD: absent palpebral reflex (V) Obtunded ↓ L-sided postural reaction deficits Obtunded Obtunded Pacing Seizures OS: absent palpebral reflex (CN V), absent corneal reflex (CN V, VI) ↓ L facial sensation (V) OS: absent palpebral reflex (CN V), absent corneal reflex (CN V) None Other neurologic signs None Diabetes mellitusAcromegaly None Inappetence Pancreatitis Coughing Weight loss L temporal m swelling Submand lymphadenopathy L nasal discharge Hypothermia Inappetence Heart murmur Anorexia Pyrexia Inappetence Weight loss Weight loss Inappetence Diarrhea Heart murmur As before Chronic hepatic lipidosis Pancreatitis Enteropathy Constipation Dehydration Inappetence Pyrexia Systemic signs ET AL. © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License BSH = British Short-hair; Burm = Burmese; CN = cranial nerve; d = days; DLH = Domestic Long-hair; DSH = Domestic Short-hair; FE = female entire; FN = female neutered; L = left; m = muscle; OD = right eye; OS = left eye; OU = both eyes; R = right; PL = pelvic limbs; submand = submandibular; TL = thoracic limbs; Tonk = Tonkinese; LN = lymph node; ME = male entire; NA = not affected; y = years. DSH 13.00 MN 5 4* 14d after Signalment Breed Age (y) Sex Table 1. Signalment and clinical signs in twelve cats with internal ophthalmoplegia/ophthalmoparesis. The affected CN is annotated in brackets 384 hamzianpour Figure 1. 6.75-year-old, male neutered, Domestic Short-hair cat (case 1) with anisocoria due to internal ophthalmoplegia of the right eye. in all four limbs (n = 3, 25%), ambulatory tetraparesis (n = 1, 8%), postural reactions deficits (n = 4, 33%), and seizures (n = 2, 17%). In addition, the neuro-ophthalmic examination included deficits in CN III (motor component), IV, V (ophthalmic and maxillary branch), VI, and VII ipsilateral to the mydriasis. Clinical signs of these deficits included the following: an absent or decreased palpebral reflex (n = 5, 42%), absent or decreased menace response with normal vision (n = 3, 25%), absent/decreased corneal reflex (n = 3, 25%), a decreased (n = 1, 8%) or absent (n = 3, 25%) vestibulo-ocular reflex (VOR) (unilateral n = 3, 25%, or bilateral n = 1, 8%), and decreased facial sensation (areas innervated by the ophthalmic and maxillary branches n = 1; 8%). Abnormal imaging findings are summarized in Table 2: MRI only (n = 4, 34%), MRI and ultrasound (n = 3, 25%), CT only (n = 1, 8%), CT and ultrasound (n = 1, 8%), CT and MRI (n = 1, 8%), and ultrasound only (n = 2, 17%). In addition, thoracic radiographs were performed in cases 2, 4, and 6. Magnetic resonance imaging (Fig. 2) or CT scans (Fig. 3) of the head were performed in most cats (n = 10, 84%). This revealed a mass lesion in all cases in varying locations: middle cranial fossa (n = 7, 58%); extra-axially between the midbrain and pons (n = 1, 8%); retrobulbar space (n = 1, 8%); and intranasally, extending to the orbital fissure (n = 1, 8%). The two cats with abdominal ultrasound only had intestinal thickening, mass-like lesions, or abnormal kidneys that were diagnosed by fine-needle aspirates and cytology as large-cell lymphoma. Their neurologic signs were suspected to be due to multicentric lymphoma, and further investigations, including MRI, were offered but declined by the owners due to quality-of-life concerns, and they requested for euthanasia of both cats. Cerebrospinal fluid (CSF) analysis was only performed in one case (case 4). CSF analysis from the cerebellomedullary cistern showed atypical large mononuclear cells (76%), small mononuclear cells (21%), nondegenerate neutrophils (1%), occasional activated macrophages (2%), and a protein concentration of 0.06 g/l. This case was diagnosed with multicentric lymphoma following fineneedle aspiration and cytology of a colonic lesion. Follow-up information is summarized in Table 2. All twelve cats were euthanized due to clinical deterioration or concerns of quality of life. There was a short-term outcome (48 h after diagnosis) of 50% survival and 50% nonsurvival. All cases with an initial short-term survival outcome were euthanized within 3 months of diagnosis. The median time between presentation and euthanasia was 3.5 days (range 0 to 80 days). Two cats had postmortem examinations performed (cases 7 and 10). Case 7 was diagnosed with a round cell neoplasm consistent with lymphoma observed in the hypothalamic area (middle cranial fossa), optic chiasm, local meninges, and stomach. This case had MRI and CT of the head performed with lesions noted on the left side of the middle cranial fossa; however, no abdominal imaging had been performed. Case 10 was diagnosed with a macroadenoma of the pituitary gland; the lesion location was consistent with the antemortem CT findings. DISCUSSION We describe clinical signs, imaging findings, and outcome in twelve cats with internal ophthalmoparesis/ophthalmoplegia. Despite several reports of middle cranial fossa syndrome in cats,7–11 this is the first case series specifically looking at the presentation of internal ophthalmoplegia/ ophthalmoparesis in cats. Understanding of the neuroanatomical pathway of CN III is important prior to interpreting its dysfunction. Cranial nerve III is divided into motor fibers and parasympathetic fibers. The motor fibers innervate the ipsilateral extra-ocular muscles (dorsal rectus, medial rectus, ventral rectus, and ventral oblique) and the ipsilateral levator palpebrae superioris muscle. The parasympathetic fibers innervate the iris sphincter and ciliary body muscles. The PLR allows evaluation of the parasympathetic fibers of CN III. Following stimulation of the retina by a light stimulus, impulses travel via the optic nerve (CN II) to the optic chiasm, where the majority of the fibers (around 65% in the cat) cross over and continue as part of the contralateral optic tract. Some optic tract fibers bypass the lateral geniculate nucleus and course caudally to synapse in the pretectal nucleus (located in the rostral midbrain). The majority of the fibers of the pretectal nucleus (around 65%) cross over to the contralateral side, through the caudal commissure, and reach the parasympathetic nucleus of CN III (known in human neuro-anatomy as the Edinger– Westphal nucleus). The remaining fibers from the pretectal nucleus (around 35%) reach the ipsilateral © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License feline internal ophthalmoplegia 385 ET AL. Table 2. Abnormal imaging findings, pathology results and outcome in twelve cats with internal ophthalmoplegia/paresis Case MRI/CT findings Other imaging findings Pathology findings Outcome 1 Abdo u/s: diffuse hepatopathy n/a Euth 5d AD n/a n/a Euth 8d AD n/a n/a Euth 0d AD 4 MRI: Extra-axial intracranial mass in the MCF through the orbital fissure bilaterally, perilesional edema and raised intracranial pressure MRI: Focal extra-axial mass extending from the ventral part of the pons to MCF L>R, with extension into the left retrobulbar tissues. MRI: Extra-axial mass lesion in the L MCF with enlargement of the three branches of CN V n/a FNA colonic mass dx large-cell lymphoma Euth 14d AD 5 n/a FNA kidney dx large-cell lymphoma Euth 1d AD 6 CT: ST thickening within L temporalis musculature extending into the retrobulbar space and in the L tympanic bulla. Fluid filling of the frontal sinuses and thickening of the lining of the L frontal sinus. CT: ST attenuating material in R tympanic bulla Mild amount of ST attenuating material in the nasal cavity. Lung consolidation MRI: Large extra-axial mass in MCF (R>L) MRI: Intranasal mass extending to the olfactory bulb, the MCF and orbital fissure MRI: Large pituitary mass extending bilaterally (R>L) CT: Large pituitary mass extending bilaterally. Thickened pancreas MRI: Large extra-axial mass in MCF (R>L) MRI: Large extra-axial mass in MCF Abdo u/s: Intramural colonic mass, intra -abdominal lymphadenopathy, hypoechoic and thickened pancreas Thoracic radiographs: mild cardiomegaly Abdo u/s: Bilateral nephropathy, mesenteric lymphadenopathy and focal intestinal thickening Abdo u/s: Polycystic hepatopathy, mesenteric lymphadenopathy, mild pancreatic disease FNA submand LN dx lymphoma Euth 70d AD n/a PM: lymphoma Euth 0d AD n/a n/a Euth 0d AD n/a n/a n/a PM: macroadenoma Euth 0d AD Euth 20d AD n/a n/a n/a n/a Euth 80d AD Euth 0d AD 2 3 7 8 9 10 11 12 AD = after diagnosis; abdo u/s = abdominal ultrasound; CN = cranial nerve; d = days; dx = diagnosis; euth = euthanized; FNA = fine-needle aspirate; n/a = not applicable; L = left; LN = lymph nodes; MCF = middle cranial fossa; PM = postmortem; R = right; submand = submandibular. parasympathetic nucleus of CN III.1,13 Both the motor and the parasympathetic fibers emerge together in the lateral aspect of the interpeduncular fossa, on the medial side of the crus cerebri, and course rostrally in the middle cranial fossa lateral to the pituitary gland, adjacent to but not in the cavernous sinus, where they meet the trochlear nerve (CN IV), abducens nerve (CN VI), and two branches of the trigeminal nerve (CN V) (ophthalmic and maxillary nerves).1,13 All these nerves (except the maxillary branch) exit the cranial cavity through the orbital fissure. The maxillary branch of CN V exits through the round foramen. The motor fibers of CN III then abruptly branch to innervate the extra-ocular muscles. Located at the point of branching is the ciliary ganglion. In this ganglion, the preganglionic parasympathetic fibers synapse onto the postganglionic parasympathetic fibers. These postganglionic fibers, then known as the short ciliary nerves, pass along the surface of the optic nerve to the eyeball to innervate the smooth muscle of the ciliary muscle and the sphincter of the pupil causing pupillary constriction (Fig. 4).1,13 Provocative pharmacological testing of mydriasis can be performed using 0.1% pilocarpine solution to assess the parasympathetic innervation of the oculomotor nerve to that eye.39 However, the results of such tests can be unreliable.40 Pharmacological testing was not performed in any of the cases of this study. Obtunded mental status was seen in nine of the twelve cats at presentation (75%). This is likely due to the intracranial masses causing compression of the forebrain/ brainstem. The menace response was absent or decreased in three cats; however, they had intact vision; the menace response deficits were considered likely to be due to their obtunded mental status. The majority of our cases (n = 8) had internal ophthalmoparesis/ophthalmoplegia without external ophthalmoparesis/plegia. Five of these eight cats (cases 1, 8, 9, 10, and 12) were diagnosed with a middle cranial fossa mass. This could be explained by the fact that the preganglionic parasympathetic fibers are more superficial, medial, and smaller in diameter than the motor fibers of CN III and therefore more at risk of being compressed by a lesion arising from the middle cranial fossa and causing mass effect.1,41,42 Two of these eight cases (cases 4 and 5) did not have advanced imaging of the head, and the remaining case (case 6) was diagnosed with a retrobulbar mass. In case 6, we could hypothesize that the mass affected mainly © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 386 hamzianpour (a) (b) (c) (d) (e) (f) Figure 2. MRI of the brain from a 6.75-year-old, male neutered, Domestic Short-hair cat with right-sided internal ophthalmoplegia (case 1) (a) and (b): mid-sagittal plane; (b), (c), (e), and (f): transverse plane at the level of the pituitary fossa plane). There is a large clearly marginated, bilobed mass in the middle cranial fossa (predominantly on the right). The mass is hyperintense, with areas of hypointensity compared to the normal gray matter on T2W FSE (a), (b) and on FLAIR (c) images. The mass is hypointense to the normal gray matter on T1W (e) and demonstrates strong contrast enhancement on T1W (d), (f). (a) (b) (c) Figure 3. Pre-contrast CT images of the brain from a 10-year-old, male neutered, Domestic Short-hair cat, with bilateral internal ophthalmoplegia with a rounded hyperattenuating large pituitary mass extending bilaterally and dorsally. Medium-frequency reconstruction images are presented in a brain window (WL 50, WW 100). (a): Transverse plane at the level of the pituitary fossa; (b): sagittal plane reconstruction; (c): dorsal plane reconstruction at the level of the middle cranial fossa. the postganglionic parasympathetic fibers after they branched away from the motor fibers. However, a postmortem examination was not obtained in this case. In cats, clinical signs of external ophthalmoparesis/ophthalmoplegia include ptosis, ventrolateral strabismus, and a decreased (paresis) or absent (plegia) VOR.13 In this case series, panophthalmoparesis/ophthalmoplegia (internal and external ophthalmoparesis/ophthalmoplegia) was only seen in the form of an ipsilateral decreased or absent VOR (n = 4); ptosis or static ventrolateral strabismus was never observed. The VOR evaluates CN VIII (sensory component to the reflex) and III, IV, and VI (motor component).39 The VOR is induced by movement of the head from side to side in a horizontal plane which elicits an involuntary rhythmic eye movement. This reflex can be decreased to absent due sensory component dysfunction (CN VIII), motor © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License feline internal ophthalmoplegia 387 ET AL. Figure 4. Neuroanatomic pathway of the pupillary light reflex. (a) Dorsal and (b) lateral views. Retina (1), optic nerve (2), optic canal (3), optic chiasm (4), optic tract (5), pretectal nucleus (6), parasympathetic component of the oculomotor nucleus (Edinger–Westphal nucleus) (7), oculomotor nerve (8), orbital fissure (9), ciliary ganglion (10), and short ciliary nerve (11). component dysfunction (CN III, CN IV, CN VI), or myopathy of the extra-ocular muscles.13 None of the cats presented with vestibular dysfunction; therefore, a dysfunction of the sensory component of this reflex was not considered the cause of the decreased/absent VOR. All four of these cats (cases 2, 3, 7, and 11) were diagnosed by MRI/ CT with a mass lesion in the middle cranial fossa. The nerves involved in the motor component of the VOR (CN III, IV, VI) pass through the middle cranial fossa where they exit the skull through the orbital fissure.13 This anatomical relationship can explain why panophthalmoparesis/ophthalmoplegia was seen in these cats. Lymphoma is the second most common intracranial neoplasm after meningioma in cats.43–45 It can be associated with feline leukemia virus.28 Lymphoma should be included as one of the major differential diagnoses in cats presented with internal ophthalmoplegia.43–45 Systemic clinical signs were seen in ten of the twelve cases in this study. Cases 4 and 5 had an abdominal ultrasound prior to MRI/CT due to the presence of inappetence, weight loss, and diarrhea (case 4). In both of these cases, due to lesions found on abdominal ultrasound, lymphoma was diagnosed by fine-needle aspiration and cytology. Due to these findings, advanced imaging was declined by the owners. This is similar to the findings of Inumura et al., who suspected CN III failure due to metastasis of a renal carcinoma. A third case, case 7, was diagnosed with intracranial and gastric lymphoma on postmortem examination. In hindsight, an abdominal ultrasound with cytology could have possibly provided a premortem diagnosis of lymphoma. As demonstrated by these cases, in cats with concurrent systemic signs abdominal ultrasound should be considered prior to any advanced imaging to better understand the clinical signs, and potentially reach a diagnosis. Inherent limitations of retrospective studies impacted these results. A final postmortem examination was only performed in two cases, thus limiting any definitive comments about the nature of our findings. The medical records were at times incomplete, although follow-up information and outcome were obtained for all cases. Another limitation of this study was the small number of cases and a referral only population. It is possible that cases presenting in general practice with feline internal ophthalmoparesis/ophthalmoplegia alone, in an otherwise healthy cat, are often not referred, and so our population is biased toward more critically unwell animals with a worse prognosis. Future prospective studies documenting larger populations of cats with internal ophthalmoparesis/ophthalmoplegia, in both a referral and first-opinion setting, would be beneficial to understand the true clinical outcome of cats with internal ophthalmoparesis/ophthalmoplegia. CONCLUSION Feline internal ophthalmoparesis/ophthalmoplegia often presents with other clinical signs in a referral hospital population. A thorough history, physical examination, and neurologic and ophthalmic examinations are essential for clinical reasoning and to effectively select the most indicated diagnostic tests. Cats with intracranial lesions can present with panophthalmoparesis/ophthalmoplegia or internal ophthalmoparesis/ophthalmoplegia as the sole clinical sign. Advanced imaging may be necessary to reach a definitive diagnosis, but abdominal ultrasound can be helpful in some cases with systemic disease. Cats with systemic and neurologic deficits related to internal ophthalmoparesis/ ophthalmoplegia have a guarded prognosis due to the high prevalence of neoplasia in this population. © 2017 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 21, 382–390 14635224, 2018, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.12523 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [09/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 388 hamzianpour CONFLICT OF INTEREST None of the authors of this article has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the article. This case report has been presented in part at the 47th Annual Conference of the American College of Veterinary Ophthalmologists, October 26–29, 2016, Monterey, California, USA. 16. 17. 18. 19. REFERENCES 1. Glass E, DeLahunta A. Lower motor neuron: general visceral efferent system. In: Veterinary Neuroanatomy and Clinical Neurology, 3rd edn. (eds. DeLahunta A, Glass E) Saunders Elsevier, St Louis, Missouri, 2009; Chapter 7, 168–191. 2. Fransson B, Kippenes H, Silver G et al. Magnetic resonance diagnosis: cavernous sinus syndrome in a dog. 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