Feline temporal lobe epilepsy: seven cases of hippocampal and piriform lobe necrosis in England and literature review

Abstract

Case series summary

Seven cases of feline hippocampal and piriform lobe necrosis (FHN) are described, with particular emphasis on clinical, radiographic and histopathological correlations. FHN is an uncommon acute epileptic condition resembling human autoimmune limbic encephalitis and temporal lobe epilepsy. Seizures are typically focal and feature uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalisation and motionless staring, with inter-ictal behavioural changes such as unprovoked aggression and rapid running. Emerging evidence supports an autoimmune aetiology, although disruption of hippocampal architecture secondary to brain neoplasia has also been recognised. Most commonly, however, the underlying cause remains unknown. Diagnosis is achieved clinically and with brain MRI; electroencephalography and voltage-gated potassium channel-complex autoantibodies are currently the subject of research. Affected cats are frequently refractory to conventional antiepileptic treatment.

Relevance and novel information

Following a review of the literature, including potential complicating factors and comparisons with human medicine, the hippocampus and piriform lobe are proposed as the neuroanatomical localisation for focal seizures with orofacial involvement in cats, regardless of aetiology.

Keywords

Hippocampal necrosis hippocampus piriform lobe necrosis temporal lobe epilepsy limbic encephalitis focal seizures

Introduction

Feline hippocampal and piriform lobe necrosis (FHN) is an acute epileptic condition characterised by focal seizures consisting of uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalisation and motionless staring lasting approximately 5–30 s. These cats usually show inter-ictal behavioural changes such as significant unprovoked aggression or rapid running.^1–7 Other less commonly reported signs are pyrexia, urinary retention, ataxia and generalised hyperaesthesia.^2,3,8–10 Neurological examination is commonly unremarkable or non-specific; diagnosis is suspected based on clinical signs, supported by MRI and confirmed on post-mortem assessment. It is currently unclear whether the lesions found are the primary cause of the seizures or whether it is the seizures themselves that result in necrosis.^{1,5,8,9,11–13} The initial focal seizures described with FHN often progress to generalised seizures and status epilepticus, and tend to be refractory to antiepileptic treatment, which frequently leads to euthanasia.^{1,2,4,9,14,15}

This study reports on seven cases of FHN in southeast England, reviews the available literature and compares it with the authors’ findings and experience.

Case series description

Inclusion criteria, timing and geographical origin

The MRI database of Dick White Referrals (Newmarket, UK) was searched for the words ‘hippocampus’, ‘hippocampal’ and ‘hippocampal necrosis’, over a 9-year period (2011–2020). Cats were included in the study if MRI abnormalities compatible with FHN had been detected by the reporting radiologist. Seven cases met the inclusion criteria. All cats were from southeast England (Essex, Norfolk and Suffolk). Cases 1–5 and 7 had access to the outdoors and, consequently, possible access to toxins; case 6 was an indoor-only cat. None of these cats had a medical history of seizures.

Signalment, history, and physical and neurological examination findings prior to imaging

Case 1

A 5-year-old male neutered (MN) domestic shorthair (DSH) cat was assessed for a 1-week history of focal seizures, which started after staying in a cattery. The specific ictal and peri-ictal clinical signs are summarised in Table 1. The following day the patient suffered a generalised tonic-clonic seizure that started with hypersalivation and lasted about 90 s. Upon reassessment, the haematology/biochemistry profile was unremarkable and the patient was subsequently referred. On presentation to our hospital, physical examination revealed mildly protruded third eyelids and a large firm bladder that was difficult to express; neurological examination revealed mildly reduced pelvic limb postural reactions (left worse than right). During the consultation, the patient suffered a focal seizure, which then escalated to a full tonic-clonic seizure. The cat was hospitalised and medications were administered (Table 2). Despite treatment, over the following 24 h the cat suffered five more focal seizures. Its bladder was found to be large, firm and difficult to express, requiring temporary urinary catheterisation.

Table 1

Representation of ictal and peri-ictal clinical signs characterising the focal seizures in our population

	Cases
	1	2	3	4	5	6	7
Hypersalivation	✓	✓	✓	✓	✓	✓	✓
Vocalisation	✓		✓	✓	✓	✓
Facial twitching	✓				✓	✓	✓
Aggressive behaviour			✓		✓		✓
Head tremors				✓	✓		✓
Mydriasis			✓		✓		✓
Agitation				✓			✓
Motionless staring		✓				✓
Sniffing			✓	✓
Circling				✓
Jaw clamping	✓
Lip licking					✓
Rigidity		✓
Sneezing	✓
Tachypnoea			✓

Table 2

Evolution of the therapeutic protocols for each case from presentation to the referring veterinary surgeon to discharge from our hospital (correlation with outcome)

Casae number	Referring veterinarian	Pre-imaging	Post-imaging	Discharge	Outcome
1	Amoxicillin, meloxicam	Dexamethasone 0.16 mg/kg q24h, levetiracetam 20–40 mg/kg q6–8h, mannitol 0.5 g/kg (single dose)	Dexamethasone 0.16 mg/kg q24h, gabapentin 12.5 mg/kg q8h, levetiracetam 20 mg/kg q8h, phenobarbital 2–3 mg/kg q4–6h (loading dose)	Dexamethasone 0.16 mg/kg q24h, gabapentin 12.5 mg/kg q8h, levetiracetam 20 mg/kg q8h, phenobarbital 2 mg/kg q12h	Recovered and seizure-free for 13 months
2	Diazepam, phenobarbital 2 mg/kg q12h	Mannitol 0.5–1.0 g/kg q5h	Dexamethasone 0.17 mg/kg q24h, diazepam 0.5 mg/kg PRN, phenobarbital 2 mg/kg q12h	NA	Euthanasia 2 days after diagnosis and 5 days after seizure onset
3	Buprenorphine, cefovecin, diazepam, maropitant	Dexamethasone 0.17 mg/kg q24h, mannitol 0.5 g/kg q4h, phenobarbital 2.1 mg/kg q12h	Dexamethasone 0.17 mg/kg q24h, phenobarbital 2.1 mg/kg q12h	Same as post-imaging	Recovered and seizure-free for 21 months, then required treatment plan revision, following which it remained seizure-free for another 12 months
4	Not available	Mannitol	Clindamycin 12.5 mg/kg q12h, dexamethasone 0.17 mg/kg q24h, levetiracetam 20 mg/kg q8h, phenobarbital 2 mg/kg q12h, vitamins B1, B2, B3, B6 and C (single injection)	Clindamycin 12.5 mg/kg q12h, dexamethasone 0.17 mg/kg q24h, levetiracetam 20 mg/kg q8h, phenobarbital 2 mg/kg q12h	Recovered and seizure-free at discharge. No follow-up available
5	Amoxicillin–clavulanate, diazepam, propofol	Mannitol 0.5 g/kg q4h, phenobarbital 2.7 mg/kg (one dose)	Amoxicillin–clavulanate 11 mg/kg q12h, cytarabine 366 mg/m² (one dose), dexamethasone 0.2–0.22 mg/kg q24h, diazepam 0.5 mg/kg PRN, phenobarbital 3.2 mg/kg q12h	NA	Euthanasia 4 days after diagnosis and 5 days after seizure onset
6	Levetiracetam 20–60 mg/kg q8h, phenobarbital 2–5.3 mg/kg q12h	Levetiracetam 20 mg/kg q8h, phenobarbital 4 mg/kg q12h	Dexamethasone 0.33 mg/kg q24h, levetiracetam 40 mg/kg q12h, phenobarbital 4 mg/kg q12h	Dexamethasone 0.33 mg/kg q24h, levetiracetam 40 mg/kg q12h, phenobarbital 6.6 mg/kg q12h	Recovered and seizure-free for 8 months
7	Diazepam	None	Dexamethasone 0.56 mg/kg once followed by 0.28 mg/kg q24h, phenobarbital 2.8 mg/kg q12h	Dexamethasone 0.28 mg/kg q24h, levetiracetam 30 mg/kg q8h, phenobarbital 2.8 mg/kg q12h	Euthanasia 15 days after diagnosis and 17 days after seizure onset

PRN = pro re nata (as required); NA = not applicable

Case 2

An 8-year-old MN DSH cat was referred following 3 days of episodic and progressively more frequent focal seizures lasting approximately 1 min (Table 1), which eventually would precede a generalised tonic-clonic seizure. Inter-ictally, the cat was subdued. On presentation, the patient was obtunded and had generalised ataxia, absent menace responses bilaterally, subjectively impaired vision, mildly reduced oculocephalic reflex bilaterally and mildly reduced postural reactions on both pelvic limbs.

Case 3

An 11-year-old MN DSH cat was assessed for sudden onset of focal seizures and diarrhoea (Table 1). On clinical examination a temperature of 39.3°C and mild-to-moderate gingivitis were noted. Over the following 24 h, the patient showed aggressive behaviour and suffered one generalised and several focal seizures. On subsequent presentation at the referral hospital, the cat was in status epilepticus and, with treatment as per Table 2, the seizures were controlled.

Case 4

A 3-year-old female spayed (FS) DSH cat was referred for multiple focal seizures and two generalised tonic-clonic seizures (Table 1), which had occurred over the previous 3 days. On presentation, physical and neurological examinations were unremarkable. After admission the patient suffered several more focal seizures lasting approximately 5–15 s, also including unprovoked hyperactivity and circling lasting approximately 2 mins; the latter seemed to be exacerbated by stress. Its temperature was 39.0°C.

Case 5

A 12-year-old MN DSH cat was assessed for the acute onset of focal seizures (Table 1). On presentation, the patient was rolling in the carrier, had passed urine and faeces, had mydriatic pupils unresponsive to light and a temperature of 41.3°C. Owing to a lack of significant response to rectal diazepam, propofol was administered. In 1 h, the patient recovered and its temperature normalised. Overnight, the cat suffered multiple focal seizures, which would stop with diazepam boluses. The following day the patient was referred. On presentation, the cat was disorientated. Physical examination disclosed a heart murmur (grade III/VI), while neurological examination revealed mildly decreased postural reactions on the left thoracic and pelvic limbs.

Case 6

An 8-year-old FS DSH cat presented to the referring veterinary surgeon for very short (5–10 s) and frequent focal seizures (Table 1). Treatment with phenobarbital (2 mg/kg q12h) was started and in 2 days the seizures stopped. The patient presented again approximately 18 months later due to seizure recurrence. The phenotype of the events was unchanged, the seizures would happen every 5–10 mins and could be controlled with diazepam boluses. On presentation, the cat’s temperature was 39.6°C. The phenobarbital dosage was initially increased to 4 mg/kg q12h but, owing to lack of improvement, over the following 36 h the dosage was increased again to 5.3 mg/kg q12h and levetiracetam was added to the treatment plan. After several doses, the patient would only hypersalivate occasionally and referral was then sought. On presentation, physical and neurological examinations only revealed anisocoria. This finding was not observed the following day.

Case 7

A 7-year-old MN DSH cat was assessed for the acute onset of agitation, unprovoked aggression towards the other cat in the household and inability to recognise the owners, which quickly progressed to more obvious focal seizures (Table 1). The patient had also been unusually lethargic and hyporexic for the previous few days and an ongoing weight loss had been noticed. On presentation, the patient was very agitated, hyper-reactive and fearful. Physical examination revealed halitosis, mild hypersalivation and subjective submandibular lymphadenomegaly. Neurological examination was limited owing to the altered mentation; the main findings were occasional head bobbing and bilateral mydriatic pupils partially responsive to light stimuli.

Diagnostic procedures

Blood tests, urinalysis and cerebrospinal fluid (CSF) analysis results can be found in Table 3; these were non-specific and, overall, unremarkable. Creatine kinase was significantly elevated, potentially owing to seizure activity (cases 4 and 5) and intramuscular sedation prior to blood collection (case 7). Urine samples were collected via urinary catheter in case 1 and via cystocentesis in cases 4, 5 and 7. CSF was collected from the cisterna magna in all patients. Brain MRI was performed in all patients under general (inhalational) anaesthesia, using a 0.4 T MRI unit (Hitachi Aperto Lucent O5). Sagittal T2-weighted (T2W) and transverse T2W, T2*, fluid attenuated inversion recovery (FLAIR), T1-weighted (T1W) and contrast-enhanced T1W images of the brain were acquired. In case 7, dorsal T2W images were additionally available and T2* was not performed in case 3. The MRI abnormalities varied from case to case (Table 4), with (T2W) hyperintensity (Figure 1) and enlargement (Figure 2) of the hippocampi commonly identified, accompanied by variable degrees of contrast enhancement (Figure 3). CSF was collected after performing imaging and under the same general anaesthesia. In case 5, a thoracic CT scan and abdominal ultrasound did not identify a cause of the seizures.

Table 3

Routine bloodwork, urinalysis and cerebrospinal fluid (CSF) analysis results

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	RI
Blood
Total protein (g/l)	72	87	66	69	70	74	64	54–78
Albumin (g/l)	32	33	29	33	32	32	32	24–39
Globulin (g/l)	40	54	37	36	38	42	32	20–45
Urea (mmol/l)	10.0	5.5	8.2	7.4	4.7	8.2	8.3	6.0–10.0
Creatinine (µmol/l)	104	96	95	98	84	103	131	40–150
Potassium (mmol/l)	3.93	4	4.4	3.8	3.2	3.1	3.8	3.5–5.6
Sodium (mmol/l)	159	162	158	148	146	160	157	138–156
Sodium:potassium ratio	40.5	NA	36	38.9	45.6	52	41.3	>27.0
Chloride (mmol/l)	121	123	118	116	114	124	125	112–129
Total calcium (mmol/l)	2.26	2.82	2.09	2.2	2.2	2.29	2.18	2.1–2.6
Inorganic phosphate (mmol/l)	1.76	1.08	0.95	1.2	1.0	0.99	1.34	1.0–2.46
Glucose (mmol/l)	5.4	4.9	6.6	9.6	6.1	6.3	6.1	4.3–6.6
ALT (IU/l)	59	117	46	74	183	85	90	30–85
AST (IU/l)	NA	NA	NA	68	1153	NA	NA	15–66
ALP (IU/l)	32	38	40	15	32	28	18	4–62
GGT (U/l)	0	1	0	0	0	0	NA	0–4
Bilirubin (µmol/l)	4	NA	4	3	4	2	5	0–10
Creatine kinase (IU/l)	NA	NA	NA	2569	522,397	NA	27,406	0–152
RBC (×10¹²/l)	7.29	8.66	7.68	5.97	8.52	7.68	7.59	7.00–11.60
Haemoglobin (g/dl)	10.9	12.2	11.8	9.0	11.9	9.7	10.5	9.0–14.0
Haematocrit (l/l)	0.34	0.37	0.31	0.29	0.35	0.30	0.320	0.29–0.46
MCV (fl)	46.0	43	41.1	47.9	40.6	39.7	41.8	37.0–47.6
MCHC (g/dl)	32.4	32.8	37.5	31.6	34.5	31.8	33.0	26.24–35.91
MCH (pg)	14.9	14.1	15.4	15.1	14.0	12.6	13.8	11.28–17.24
WCC (×10⁹/l)	5.88	7.56	11.25	13.16	13.02	11.79	8.56	5.5–19.5
Neutrophils (×10⁹/l)	4.30	5.72	7.43	11.71	11.69	6.29	7.74	2.5–12.5
Lymphocytes (×10⁹/l)	1.16	0.88	2.55	1.05	1.11	4.37	0.44	1.5–7.0
Monocytes (×10⁹/l)	0.12	0.17	0.76	0.39	0.17	0.18	0.29	0.0–1.0
Eosinophils (×10⁹/l)	0.30	0.72	0.49	0.00	0.05	0.64	0.06	0.0–1.5
Basophils (×10⁹/l)	0.01	0.06	0.03	0.00	0	0.31	0.02	0.0–0.1
Platelets (×10⁹/l)	240	493	862	250	320	N/A	309	250–800
FIV and FeLV SNAP test	Negative					Negative	Negative
Toxoplasma gondii IgM titre	Negative					Negative	Negative
Toxoplasma gondii IgG titre	Negative					Negative	Positive at 1:400
FeCoV titre	0					1280	0
AGP (µg/ml)	363					595	<300	<500
Fasting ammonia (µmol/l)				28.8				5–44
Pre-prandial bile acids (µmol/l)				1.5				0–10
Post-prandial bile acids (µmol/l)				3.6				0–15
TT4 (nmol/l)							22	10–60
Urine
USG	1.025	NA	NA	1.025	1.032	NA	>1.050	1.035–1.060
pH	7.0	NA	NA	7.5	7.0	NA	6.5	5.5–7.5
Protein	Negative	NA	NA	Negative	++	NA	+
Nitrite	Negative	NA	NA	Negative	Negative	NA	Negative
Blood/haemoglobin	Negative	NA	NA	Negative	+++	NA	+
Glucose	Negative	NA	NA	Negative	Negative	NA	++
Ketones	Negative	NA	NA	Traces	Negative	NA	Negative
Bilirubin	Negative	NA	NA	Negative	Negative	NA	Negative
Red cells (/hpf)	3–5	NA	NA	Occasional	1–3	NA	<1	0–2
White cells (/hpf)	<1	NA	NA	<1	<1	NA	<1	0–2
Epithelial cells (/hpf)	<1	NA	NA	1–5	<1	NA	<1	0–5
Casts	Negative	NA	NA	Negative	Negative	NA	Negative
Crystals	Negative	NA	NA	Negative	Negative	NA	Negative
Bacteria	Negative	NA	NA	Negative	Negative	NA	Negative
CSF
Protein (g/l)	0.12	0.47	0.12	0.11	0.16	0.07	2.65	0.08–0.36
Nucleated cell count (/µl)	1	5	<1	<1	1	1	<1	0–6
Red cell count (/µl)	1	13,050	<1	<1	6	<1	20,500	0
Cytological evaluation	Unremarkable	Iatrogenic blood contamination	6 neutrophils out of a total of 32 nucleated cells	Unremarkable	Unremarkable	Few reactive lymphocytes	Iatrogenic blood contamination
RT-PCR for infectious agents*		Negative		Negative		Negative

Case 2 was tested for Toxoplasma gondii, bornavirus, parvovirus and feline coronavirus (FeCoV). Case 4 was tested for feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), feline herpesvirus, calicivirus, Bordetella species, Chlamydophila species, Toxoplasma gondii, bornavirus, Leishmania infantum and parvovirus. Case 6 was tested for FeCoV

RI = reference interval; NA = not applicable; ALT = alanine transaminase; AST = aspartate transaminase; ALP = alkaline phosphatase; GGT = gamma-glutamyl transferase; RBC = red blood cells; MCV = mean cell volume; MCHC = mean cell haemoglobin concentration; MCH = mean cell haemoglobin; WCC = white cell count; AGP = alpha-1-acid glycoprotein; TT4 = total thyroxine; USG = urine specific gravity; hpf = high-power field; RT-PCR = reverse transcription PCR

Table 4

MRI findings for the reported cases

Case number	MRI findings
1	The area of the hippocampus and piriform lobe was bilaterally and symmetrically mildly hyperintense on T2W and FLAIR images, compared with cortical grey matter, remaining isointense on T1W images, with the right piriform lobe slightly larger than the left (Figure 2b). There was faint contrast enhancement of the hippocampi (Figure 3a).
2	The region of the hippocampus and piriform lobe was bilaterally and symmetrically mildly hyperintense on T2W and FLAIR images, compared with cortical grey matter, remaining isointense on T1W images. There was one faint region of contrast enhancement in the body of the left hippocampus only.
3	The area of the hippocampus and piriform lobe was bilaterally asymmetrically hyperintense on T2W and FLAIR images, compared with cortical grey matter (Figure 1b), remaining isointense on T1W images. There was a focal yet asymmetric region of contrast enhancement in the left hippocampus with a more diffuse faint patchy contrast enhancement of other portions of the hippocampus (Figure 3b). The sulci were deep, with increased CSF surrounding the cerebrum.
4	The area of both hippocampi and piriform lobes was strongly and bilaterally symmetrically hyperintense on T2W and FLAIR images, compared with cortical grey matter (Figure 1a), remaining isointense on T1W images. The entire area was subjectively symmetrically enlarged (Figure 2a). Small patches of faint contrast enhancement were noted, more notably in the right hippocampus.
5	There was marked swelling and hyperintensity of the left hippocampus with strong focal contrast enhancement (suspected location of the astrocytoma); however, there was also some milder hyperintensity and enlargement of the right one. On histopathology, this lesion was compatible with a fibrillary astrocytoma (Figure 5).
6	The area of the hippocampus and piriform lobe was bilaterally and symmetrically mildly hyperintense on T2W and FLAIR images, compared with cortical grey matter, remaining isointense on T1W images and without contrast enhancement.
7	There was marked swelling and variable, but in places strong, contrast enhancement of the right hippocampus, with similar but less dramatic changes in the left hippocampus. On histopathology this lesion was compatible with a lymphoma (Figure 6).

T2W = T2 weighted; FLAIR = fluid attenuated inversion recovery; T1W = T1 weighted; CSF = cerebrospinal fluid

Figure 1

Examples of T2-weighted (T2W) signal change. T2W and fluid attenuated inversion recovery transverse images at the level of the hippocampus are shown from two cases. (a) Strong and bilaterally symmetric hyperintensity in both hippocampi (case 4). (b) Asymmetric T2W hyperintensity (arrows) in the left hippocampus (case 3).

Figure 2

Examples of enlargement of the hippocampi. T2-weighted and fluid attenuated inversion recovery transverse images at the level of the hippocampus are shown from two cases. (a) Symmetric marked enlargement of both hippocampi (arrows) (case 4); (b) mild enlargement of the right hippocampus most apparent as it becomes larger than the left (arrowheads) (case 1).

Figure 3

Examples of contrast enhancement of the hippocampi. T1-weighted (T1W), T1W post-contrast and subtraction transverse images at the level of the hippocampi are shown from two cases. (a) Contrast enhancement may be subtle (best identified on the subtraction images, arrowheads) yet diffuse (case 1). (b) Focal yet asymmetric region of contrast enhancement in the left hippocampus (arrow) with a more diffuse faint patchy contrast enhancement of other portions of the hippocampus (arrowheads) (case 3).

Treatment, outcome and follow-up

The therapeutic protocols for each patient are summarised in Table 2.

Case 1

During hospitalisation, an indwelling urinary catheter was placed for bladder management. Over 4 days following the initiation of treatment, seizure frequency decreased, and at the time of discharge the patient had not had any seizure for approximately 48 h. Four weeks later the patient was still seizure-free and treatment with gabapentin was discontinued. The dexamethasone dosage was tapered over the following 3 months. The cat remained seizure-free for the following 9 months. No further follow-up was available.

Case 2

Following diagnosis, treatment with dexamethasone was started and treatment with phenobarbital was continued. Shortly after recovering from anaesthesia, the patient suffered a progressively higher number of focal seizures lasting 10–60 s, which would only temporarily stop with diazepam. At that point the owners elected for euthanasia and consented to post-mortem examination.

Case 3

The patient was discharged the day after investigations. For the following 2 months it remained seizure-free, therefore dexamethasone was tapered and stopped. Nineteen months later the cat started to suffer seizures again every 2–3 weeks. At that point phenobarbitone serum levels were 5 mg/l (reference interval [RI] 15–30) and the dosage was increased. For 1 year after this relapse, the patient remained seizure-free. The phenobarbital dosage was therefore decreased with a plan of stopping the medication within the following 6 months. No further follow-up beyond 3 years was available.

Case 4

The seizures proved difficult to control initially, but their frequency and severity reduced after a loading dose of phenobarbitone, levetiracetam and dexamethasone. The patient was also pre-emptively started on clindamycin. Four days after presentation, while hospitalised, the patient became dysuric and needed manual bladder expressions. Urinalysis and urine culture were unremarkable at that stage (see Table 3). Once recovered and seizure-free, the cat was discharged. No follow-up was available.

Case 5

The cat continued to have frequent focal seizures, which would stop only temporarily with diazepam and additional doses of phenobarbital. The patient also became pyrexic again with temperatures oscillating between 39.9°C and 40.7°C. Cytosine arabinoside was administered; however, over the following 24 h the cat continued to suffer a series of approximately 20–25 focal seizures, which could no longer be controlled. Furthermore, the cat’s bladder became consistently large, firm and very difficult to express. The owners elected euthanasia and a post-mortem examination was performed.

Case 6

Following diagnosis, the treatment plan was changed as per Table 2. At this point, phenobarbital and levetiracetam blood concentrations were, respectively, 17 mg/l (RI 15–30) and 26 mg/l (RI 5.5–21.0). After being seizure-free for 48 h, the patient was discharged. Over the following months, the cat remained seizure-free, while dexamethasone and phenobarbital were slowly tapered. At the time of writing the patient was still under treatment and has been seizure-free for 10 months.

Case 7

After starting dexamethasone and phenobarbital a gradual improvement was noticed, with only occasional focal seizures, normal appetite and behaviour. Levetiracetam was added to the therapeutic plan and the patient was subsequently discharged. The day after discharge, dexamethasone was increased back to 0.56 mg/kg q24h owing to seizure reoccurrence, after which the seizures stopped. Two weeks later, the cat was rechecked owing to acute lethargy, weakness, hyporexia and vacant mentation. On presentation, the patient was markedly obtunded and barely responsive. It had lost 5% of its body weight compared with 2 weeks before and a pyrexia of 39.9°C was also noted. On neurological examination it was circling to the left, head pressing and showed reduced palpebral reflex, pupillary light reflex and menace response bilaterally. At this point the patient was euthanased and a post-mortem examination was performed.

Post-mortem examination

Case 2

Microscopically, there was, bilaterally, symmetrical, multifocal, neuronal degeneration and necrosis with mild gliosis and mild perivascular cuff formation within the piriform lobes and the dentate gyri of the hippocampus, compatible with FHN.

Case 5

Histopathology of the brain revealed severe, acute, multifocal neuronal necrosis and chromatolysis with a focal proliferation of spindle cells between the left piriform lobe and the hippocampus, compatible with a fibrillary astrocytoma, to which the neuronal changes were potentially secondary. No significant inflammatory reaction was observed.

Case 7

Macroscopic examination of the brain revealed a poorly demarcated expansion of the hippocampal region and piriform lobe, which was solid, light brown and predominantly localised to the right side. Microscopically, disrupting, expanding and replacing the neuroparenchymal architecture at the level of the hippocampus, internal capsule and piriform lobe was a poorly demarcated, non-encapsulated, highly infiltrative and densely cellular neoplastic process, compatible with lymphoma (Figure 4). The neoplastic cells expanded the Virchow robin space in the adjacent neuroparenchyma, forming cuffs up to six cells thick, and were present within the meninges multifocally, ventricles and expanding the choroid plexus.

Figure 4

Case 7: transverse section of the brain post-fixation. There is a poorly demarcated expansion (asterisk) in the region of the hippocampus and piriform lobe on the right, which is solid and light brown with darker brown foci and causes a midline shift. On histopathology, this lesion was compatible with a lymphoma

Discussion

FHN has been reported in one publication as a relatively frequent aetiology for feline seizures, ranging between 11% and 25%.⁵ Other authors considered it a rare disease or did not mention it among the causes of feline seizures at all.^13,14,16 The aetiology of FHN remains unclear: there is some evidence supporting a vascular insult as the primary cause of the disease;^4,17 however, the aetiology remains most frequently unknown. A neoplastic process affecting the brain and secondarily damaging the hippocampus can be considered as a differential diagnosis. Oligodendrogliomas and meningiomas have been found to cause clinical signs compatible with FHN, also in the absence of MRI findings.^4,18,19 In our case series, fibrillary astrocytoma and lymphoma were diagnosed in cases 5 and 7 (Figures 5 and 6); to the best of our knowledge, these neoplasms have not previously been reported to cause focal seizures compatible with FHN. An immune-mediated inflammatory process has also been hypothesised.² A link between voltage-gated potassium channel (VGKC) complex antibodies and FHN has been defined,^10,20,21 similarly to autoimmune limbic encephalitis (LE) causing temporal lobe epilepsy (TLE) in humans.^22–24 The autoantibodies seem to be targeting leucine-rich glioma inactivating factor 1 (LGI1), which is the main known component of the VGKC complex and is strongly expressed in the hippocampal neuropil.¹⁰ Interference with LGI1 is thought to impair its function as a VGKC complex modulator causing neuronal hyperexcitability,¹⁰ hence the seizures. Another study conducted in a cat detected a similar autoimmune response towards other antigens leading to FHN in the absence of antibodies against the VGKC complex/LGI1.²⁵ In patients without evidence of inflammation on MRI, CSF and histopathology (such as case 2), it should be considered that neuronal necrosis secondary to autoimmune phlogosis could lack typical inflammatory features at later stages of disease or following treatment. In humans, 20% of LE with VGKC complex antibodies is paraneoplastic;²³ a similar link has not been demonstrated to date in cats. The fact that different aetiologies have been associated with similar presentations suggests that the characteristic phenotype of FHN is indicative of a neurolocalisation in the region of the hippocampus and piriform lobe, rather than a specific condition. In view of the documented susceptibility of the hippocampus to hypoxic insults,^26,27 it seems reasonable to hypothesise that any process causing some degree of compression or disruption to the architecture of this neuroanatomical region could lead to focal ischaemia and necrosis.

Figure 5

Case 5, diagnosed with astrocytoma, and concurrent evidence of hippocampal necrosis. T2-weighted/fluid attenuated inversion recovery (top row) and T1/T1-weighted post-contrast (bottom row) transverse images taken at the level of the hippocampus demonstrate a marked swelling and hyperintensity of the left hippocampus with strong focal contrast enhancement (arrows, suspected location of the astrocytoma), and also some milder hyperintensity and enlargement of the right one (arrowheads).

Figure 6

Case 7, diagnosed with intracranial lymphoma. T2-weighted/fluid attenuated inversion recovery (top row) and T1/T1-weighted post-contrast (bottom row) transverse images taken at the level of the hippocampus demonstrate that there is marked swelling (arrows) and variable but in places strong contrast enhancement (arrowheads) of the right hippocampus, with similar but less dramatic changes in the left hippocampus (out of plane).

Although some reports suggest an infectious aetiology as the primary cause of FHN, no known infectious agent has ever been found, which was consistent with our cases. Case 6 showed increased feline coronavirus (FeCoV) serum titres and alpha-1-acid glycoprotein, but this was not deemed significant in view of the reverse transcription PCR (RT-PCR) results on CSF. The latter test has been reported to have sensitivity of up to 42% and specificity of 100% for the diagnosis of feline infectious peritonitis.²⁸ Furthermore, all patients were negative for the remaining known infectious causes of feline encephalitis. Considering the commonly reported pyrexia in feline and human patients with LE, which was also detected in some of our patients, a prodromal and self-limiting infection causing an autoimmune response via the mechanism of molecular mimicry cannot be excluded.^21,29 Timing between the onset of clinical signs and presentation can be crucial in detecting pyrexia, as this may be associated with the acute phase of the disease. Interestingly, in both our patients with histopathologically confirmed neoplasia (cases 5 and 7), pyrexia re-occurred and/or persisted after diagnosis, while, in case 6, pyrexia was detected upon seizure re-exacerbation. Non-convulsive status epilepticus should therefore be considered as another, more likely, explanation for re-occurring pyrexia in these cases. An electroencephalogram (EEG) could also be used to reach this conclusion and guide treatment.³⁰

In another study, an environmental trigger such as an unknown toxin was also considered, especially in view of the fact that the reported patients were all from the same area.¹ Although this option cannot be disregarded for most of our patients, who were also outdoor cats, toxicity represents a less likely explanation for indoor cats,^9,14 such as case 6.

To date, there is controversial evidence as to whether FHN represents a cause or a consequence of severe seizures.^{1,5,8,9,11–13,20,25} Despite this, the correlation between progression of the disease and severity of the epileptic events seems to indicate that FHN is the origin of the epileptic activity. This idea is supported by several facts. First, there is convincing experimental evidence in laboratory cats that progressive kindling of the hippocampus causes autonomic, motor and behavioural signs virtually identical to the ones suffered by FHN patients, finally resulting in generalised seizures (Table 5).^31–33 Second, in cats with naturally occurring FHN, the focal seizures often progress into generalised seizures, as reported for cases 1, 2 and 4. In some cases, the focal phase may be too short to be noticed before generalisation into a tonic-clonic seizure. This worsening of the clinical condition in naturally occurring FHN matches the progression reported in experimental settings. Lastly, although some authors report the typical FHN MRI changes as post-ictal,⁸ this is debatable as post-ictal MRI changes have not been described in cats, as opposed to dogs and humans.^34–37 In the light of this, the possibility that FHN is a consequence of intense seizure activity is less likely. Nonetheless, more research investigating post-ictal MRI changes in epileptic cats is needed to further evaluate this possibility.

Table 5

Previously proposed clinical staging system for experimentally induced feline hippocampal and piriform lobe necrosis seizures compared with the presented cases

	Sato (experimentally induced)³³	Our cases (naturally occurring)
Stage 1	Arrest of ongoing behaviour, meowing, looking around, sniffing
Stage 2	Immobility (staring and arrest)
Stage 3	Autonomic manifestation: salivation, licking, pupillary dilation
Stage 4	Facial twitching, masticatory movements	Cases 5 and 6
Stage 5	Tonic extension of contralateral paw, head nodding, head turning	Case 7
Stage 6	Generalised clonic convulsion in lateral recumbency	Cases 1, 2, 3 and 4

In human medicine, the most typical manifestation of LE and secondary TLE is represented by focal seizures consisting of sensations of fear or rage, oro-alimentary automatisms, mydriasis, hypersalivation, hyperventilation and heart rate changes.^38,39 Human LE is thought to be mediated by VGKC complex antibodies;²³ the latter are also associated with facial or faciobrachial dystonic seizures,^21,22 which resemble the typical clinical presentation of FHN. Pakozdy et al found concentrations of VGKC complex antibodies greater than the human RIs in 36% of a group of cats with clinical signs compatible with FHN.²⁰ Moreover, autoantibodies against the ‘deleted in colorectal cancer’ protein were found in a feline patient with clinical signs and MRI findings compatible with FHN, in the absence of VGKC complex antibodies.²⁵ These results suggest that even within the possibility of an autoimmune LE causing FHN, different autoantibodies may be involved in the feline population, requiring further investigations in future research.

Typically, in FHN patients undergoing MRI, the hippocampus and the piriform lobes are T2 and FLAIR hyperintense, T1 hypointense and can show contrast enhancement.¹⁵ The lesions can be homogenous, affecting the organ in its entirety, or only focal.¹⁸ Despite the peculiar presentation, a diagnosis can only be postulated based on clinical presentation and/or MRI until pathology is performed (most commonly post mortem). Timing of MRI acquisition in respect to the onset of the clinical signs can also be relevant, as imaging findings are not consistent at different stages of the disease.⁹ In our population, except for case 6, advanced neuroimaging was performed soon after seizure onset (median 3 days; range 559 days). In case 6, MRI was performed approximately 18 months after the first seizure and 2 days after acute seizure re-exacerbation. Unfortunately, it is impossible to establish whether imaging performed within the first days after the very first seizures would have revealed more marked changes. Specific three-dimensional volumetric sequences have been used to assess for hippocampal atrophy and asymmetry in feline limbic epilepsy,⁴⁰ and can be crucial for their detection if the lesions are subtle; however, altered size or asymmetry was noted in four of our seven cases on standard sequences. There was also no evidence of further structural disease beyond the hippocampal changes and the asymmetry was always thought to be due to asymmetric oedema rather than atrophy.

Peri-ictal urinary dysfunction has rarely been reported in cats suffering with FHN.^8,10 In our cases, bladder management was difficult in cases 1, 4 and 5. This is an uncommon finding and, to our knowledge, it has only been reported in a few other cats.^8,10 Feline interstitial cystitis has been proposed as the underlying process causing urinary retention in these patients: autonomic dysfunction, hippocampal changes secondary to chronic stress and stress caused by hospitalisation or the disease itself are all possible pathophysiological mechanisms.^10,41 In human medicine, epileptic patients can suffer from different post-ictal urinary issues, with the most common one being incontinence (24.3%) and urinary retention being reported by up to 8.7% of epileptic patients.^42,43 Urinary dysfunction is also more common in those suffering from focal seizures.⁴² Aural urinary urge is reported in patients suffering from TLE,^44,45 and an ictal urinary urge epileptogenic zone could be localised to the temporal lobe by invasive subdural EEG.⁴⁴ Further research is needed to define the pathophysiology underlying this process in feline patients; however, when treating FHN, the clinical consequences of an interstitial cystitis should be considered as a potential complicating factor.

EEG has been performed inter-ictally in cats with FHN. Although some patients had a normal EEG,^2,9 in human medicine ictal scalp EEG is normal in 60% of patients with TLE.⁴⁶ In two cats the abnormalities detected were primarily located in the left occipital lobe,^9,10 with spread to the same side; Kuwabara et al detected inter-ictal spikes and sharp waves in the temporal–parietal regions of 14 cats with seizure semiology similar to our cases.⁴⁷ EEG can also determine whether a patient is ictal, and it has been used to detect non-convulsive status epilepticus and successfully guide treatment in a cat.³⁰ In human medicine, patients with TLE represent nearly 70% of all epilepsy patients treated with tailored brain resection,⁴⁸ and 80% of those patients with TLE show seizure freedom for at least 2 years postoperatively.⁴⁹ If EEG is performed and interpreted more confidently and reliably in cats in the future, similar surgical techniques could also be developed in veterinary medicine.

To our knowledge, there are only a few reports of abnormal CSF in cats with FHN: in one case, CSF protein and nucleated cell count were mildly to moderately increased with mixed pleocytosis. RT-PCR did not detect feline immunodeficiency virus, feline leukaemia virus FeCoV or Toxoplasma gondii in CSF, and only showed a very weak positivity for parvovirus. The latter finding was considered secondary to sample contamination.⁵⁰ In a cat with histologically confirmed piriform lobe oligodendroglioma, CSF protein was mildly increased,¹⁹ while in another feline patient mild pleocytosis with mononuclear predominance was detected.² In our patients, cisternal CSF analysis did not show any significant anomalies, similarly to other reports.^1,2,9,14,15 The absence of pleocytosis or other significant CSF abnormalities does not rule out several infectious and non-infectious diseases of the central nervous system;⁵¹ therefore, in patients with FHN, CSF analysis should always be correlated with neuroimaging and clinical findings.

Treatment of FHN is frequently challenging and this often leads to euthanasia.^{1,2,4,9,14,15} Affected cats should be treated promptly in the attempt of limiting the degree of hippocampal sclerosis, which represents a crucial element for pharmacoresistance.^4,18 According to some reports,^3,10,20,21 antiepileptic drugs (AEDs) seem to result in reduced seizure frequency and/or severity if associated with corticosteroids. Medications such as dexamethasone and prednisolone act as anti-inflammatory, anti-oedemigenous and immunosuppressive agents, and may be beneficial regardless of whether immune-mediated inflammation or neoplasia is suspected. However, more studies are necessary to define whether corticosteroids are truly advantageous in the treatment of FHN. In our cases, treatment with dexamethasone was administered to all seven patients and therefore no control individuals receiving AEDs only were available. The majority of the patients experienced a significant improvement. In case 2, it is unclear whether treatment should have been started earlier or at higher doses to limit such an extensive degree of necrosis. Cases 5 and 7 were refractory to treatment and this was likely due to the neoplastic nature of their condition.

Conclusions

FHN is a newly described disease characterised by acute focal seizures resembling human autoimmune LE and TLE. The aetiology is unclear; growing evidence supports an autoimmune nature in cats as well, although disruption of hippocampal architecture secondary to brain neoplasia has also been found. Diagnosis is currently achieved clinically and with brain MRI. The use of EEG and the interpretation of VGKC/LGI1 autoantibodies detection are currently being investigated and may allow a more confident ante-mortem diagnosis in the future. Based on the literature and our clinical experience, treatment should consist of AEDs in conjunction with immunosuppressive doses of corticosteroids. Our study contributes to the existing literature by reporting seven further cases of FHN and their diagnostic and therapeutic plan, by reviewing the available research and by proposing the hippocampus and piriform lobe as neuroanatomical structures that, if damaged, can lead to distinct focal seizures in cats, regardless of the underlying aetiology. In fact, we describe two cases with MRI findings indicative of FHN and post mortem suggesting neoplasia, meaning that even with specific imaging characteristics, different aetiologies should be considered. Pyrexia and peri-ictal urinary dysfunction are also important findings and potential complicating factors that should be accounted for when managing FHN.

Footnotes

Accepted: 5 July 2021

Conflict of interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

This work involved the use of non-experimental animals only (including owned or unowned animals and data from prospective or retrospective studies). Established internationally recognised high standards (‘best practice’) of individual veterinary clinical patient care were followed. Ethical approval from a committee was therefore not specifically required for publication in JFMS.

Informed consent

Informed consent (either verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work for the procedure(s) undertaken. No animals or humans are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Bruno Scalia

Abby Caine

References

Fatzer

Gandini

Jaggy

, et al. Necrosis of hippocampus and piriform lobe in 38 domestic cats with seizures: a retrospective study on clinical and pathologic findings. J Vet Intern Med 2000; 14: 100–104.

Pakozdy

Gruber

Kneissl

, et al. Complex partial cluster seizures in cats with orofacial involvement. J Feline Med Surg 2011; 13: 687–693.

Adagra

Piripi

SA.

Hippocampal necrosis in a cat from Australia.

Case Rep Vet Med 2014. DOI: 10.1155/2014/306789.

Klang

Högler

Nedorost

, et al. Hippocampal necrosis and sclerosis in cats: a retrospective study of 35 cases. Acta Vet Hung 2018; 66: 269–280.

Pákozdy

Leschnik

Sarchahi

, et al. Clinical comparison of primary versus secondary epilepsy in 125 cats. J Feline Med Surg 2010; 12: 910–916.

Hazenfratz

Taylor

SM.

Recurrent seizures in cats: diagnostic approach – when is it idiopathic epilepsy?

J Feline Med Surg 2018; 20: 811–823.

Moore

Seizures and epilepsy in cats.

Vet Med (Auckl) 2014; 5: 41–47.

Marioni-Henry

Monteiro

Behr

Complex partial orofacial seizures in English cats.

Vet Rec 2012; 170: 471. DOI: 10.1136/vr.e3140.

Fors

Meervenne

Jeserevics

, et al. Feline hippocampal and piriform lobe necrosis as a consequence of severe cluster seizures in two cats in Finland. Acta Vet Scand 2015; 57. DOI: 10.1186/s13028-015-0127-x.

10.

Pakozdy

Glantschnigg

Leschnik

, et al. EEG-confirmed epileptic activity in a cat with VGKC-complex/LGI1 antibody-associated limbic encephalitis. Epileptic Disord 2014; 16: 116–120.

11.

Wahle

Brühschwein

Matiasek

, et al. Clinical characterization of epilepsy of unknown cause in cats. J Vet Intern Med 2014; 28: 182–188.

12.

Pakozdy

Halasz

Klang

Epilepsy in cats: theory and practice.

J Vet Intern Med 2014; 28: 255–263.

13.

Raimondi

Shihab

Gutierrez-Quintana

, et al. Magnetic resonance imaging findings in epileptic cats with a normal interictal neurological examination: 188 cases. Vet Rec 2017; 180: 610. DOI: 10.1136/vr.104142.

14.

Brini

Gandini

Crescio

, et al. Necrosis of hippocampus and piriform lobe: clinical and neuropathological findings in two Italian cats. J Feline Med Surg 2004; 6: 377–381.

15.

Schmied

Scharf

Hilbe

, et al. Magnetic resonance imaging of feline hippocampal necrosis. Vet Radiol Ultrasound 2008; 49: 343–349.

16.

Schriefl

Steinberg

Matiasek

, et al. Etiologic classification of seizures, signalment, clinical signs, and outcome in cats with seizure disorders: 91 cases (2000–2004). J Am Vet Med Assoc 2008; 233: 1591–1597.

17.

Gelberg

HB.

Diagnostic exercise: sudden behavior change in a cat.

Vet Pathol 2013; 50: 1156–1157.

18.

Wagner

Rosati

Molin

, et al. Hippocampal sclerosis in feline epilepsy. Brain Pathol 2014; 24: 607–619.

19.

Vanhaesebrouck

Posch

Baker

, et al. Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis. J Feline Med Surg 2012; 14: 932–937.

20.

Pakozdy

Halasz

Klang

, et al. Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody. J Vet Intern Med 2013; 27: 212–214.

21.

Klang

Schmidt

Kneissl

, et al. IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies. J Neuropathol Exp Neurol 2014; 73: 403–413.

22.

Irani

Michell

Lang

, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69: 892–900.

23.

Toledano

Pittock

Autoimmune epilepsy.

Semin Neurol 2015; 35: 245–258.

24.

Bien

Urbach

Schramm

, et al. Limbic encephalitis as a precipitating event in adult-onset temporal lobe epilepsy. Neurology 2007; 69: 1236–1244.

25.

Hasegawa

Ohnishi

Koyama

, et al. Deleted in colorectal cancer (netrin-1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis. J Vet Intern Med 2019; 33: 1440–1445.

26.

Kreisman

Soliman

Gozal

Regional differences in hypoxic depolarization and swelling in hippocampal slices.

J Neurophysiol 2000; 83: 1031–1038.

27.

Auer

Dunn

Sutherland

Hypoxia and related conditions. In: Love

Louis

Ellison

(eds). Greenfield’s neuropathology. London: Hodder Arnold, 2008, pp 63–119.

28.

Doenges

Weber

Dorsch

, et al. Detection of feline coronavirus in cerebrospinal fluid for diagnosis of feline infectious peritonitis in cats with and without neurological signs. J Feline Med Surg 2016; 18: 104–109.

29.

Cusick

Libbey

Fujinami

RS.

Molecular mimicry as a mechanism of autoimmune disease.

Clin Rev Allergy Immunol 2012; 42: 102–111.

30.

Cuff

Bush

Stecker

, et al. Use of continuous electroencephalography for diagnosis and monitoring of treatment of nonconvulsive status epilepticus in a cat. J Am Vet Med Assoc 2014; 244: 708–714.

31.

Kitz

Thalhammer

Glantschnigg

, et al. Feline temporal lobe epilepsy: review of the experimental literature. J Vet Intern Med 2017; 31: 633–640.

32.

Wada

Sato

Corcoran

ME.

Persistent seizure susceptibility and recurrent spontaneous seizures in kindled cats.

Epilepsia 1974; 15: 465–478.

33.

Sato

Hippocampal seizure and secondary epileptogenesis in the ‘kindled’ cat preparations.

Psychiatry Clin Neurosci 1975; 29: 239–250.

34.

Mellema

Koblik

Kortz

, et al. Reversible magnetic resonance imaging abnormalities in dogs following seizures. Vet Radiol Ultrasound 1999; 40: 588–595.

35.

Yaffe

Ferriero

Barkovich

, et al. Reversible MRI abnormalities following seizures. Neurology 1995; 45: 104–108.

36.

Chan

Chin

SSM

Kartha

, et al. Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures. Am J Neuroradiol 1996; 17: 1725–1731.

37.

Sun

Zhu

Wang

, et al. Epileptic seizures with reversible lesions in bilateral frontoparietal lobes: a case report and literature review. J Int Med Res 2017; 45: 1435–1439

38.

Engel

Introduction to temporal lobe epilepsy.

Epilepsy Res 1996; 26: 141–150.

39.

Janszky

Fogarasi

Toth

, et al. Peri-ictal vegetative symptoms in temporal lobe epilepsy. Epilepsy Behav 2007; 11: 125–129.

40.

Mizoguchi

Hasegawa

Kuwabara

, et al. Magnetic resonance volumetry of the hippocampus in familial spontaneous epileptic cats. Epilepsy Res 2014; 108: 1940–1944.

41.

Roy

Green

AL.

The central autonomic network and regulation of bladder function.

Front Neurosci 2019; 13: 535.

42.

Motamedi

Nikoobakht

Aloosh

, et al. Peri-ictal urinary dysfunction in patients with epilepsy: a cross-sectional study. Urol J 2011; 8: 222–226.

43.

Vander

Ifergane

Transient postictal urinary retention: presentation of three cases.

Eur J Neurol 2004; 11: 207–208.

44.

Gurgenashvili

Massey

Grant

, et al. Intracranial localisation of ictal urinary urge epileptogenic zone to the non-dominant temporal lobe. Epileptic Disord 2011; 13: 430–434.

45.

Baumgartner

Groppel

Leutmezer

, et al. Ictal urinary urge indicates seizure onset in the nondominant temporal lobe. Neurology 2000; 55: 432–434.

46.

Wieser

H-G

, ILAE Commission on Neurosurgery of Epilepsy. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 2004; 45: 694–714.

47.

Kuwabara

Hasegawa

Ogawa

, et al. A familial spontaneous epileptic feline strain: a novel model of idiopathic/genetic epilepsy. Epilepsy Res 2010; 92: 85–88.

48.

Téllez-Zenteno

Hernández-Ronquillo

A review of the epidemiology of temporal lobe epilepsy.

Epilepsy Res Treat 2012; 2012: 630853.

49.

Blümcke

Pauli

Clusmann

, et al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 2007; 113: 235–244.

50.

Yanai

Palus

Caine

, et al. Feline idiopathic hippocampal necrosis: findings in a UK case. Available at: https://www.vettimes.co.uk/app/uploads/wp-post-to-pdf-enhanced-cache/1/feline-idiopathic-hippocampal-necrosis-findings-in-a-uk-case.pdf (2013, accessed July 14, 2021).

51.

Levine

Cook

. Cerebrospinal fluid and central nervous system cytology. In: Valenciano

Cowell

(eds). Cowell and Tyler’s diagnostic cytology and hematology of the dog and cat. St Louis, MO: Elsevier, 2020, pp 210–228.