Abstract
Case series summary
This was a retrospective study on the clinical features and response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and tail mutilation. FHS is a poorly understood disorder characterised by skin rippling over the dorsal lumbar area, episodes of jumping and running, excessive vocalisation, and tail chasing and self-trauma. The majority of the cats were young, with a median age of 1 year at the onset of clinical signs, male (n = 6) and with access to the outdoors (n = 5). Multiple daily episodes of tail chasing and self-trauma were reported in five cats, with tail mutilation in four cats. Vocalisation during the episodes (n = 5) and rippling of lumbar skin (n = 5) were also reported. Haematology, serum biochemistry, Toxoplasma gondii and feline immunodeficiency virus/feline leukaemia virus serology, MRI scans of brain, spinal cord and cauda equina, cerebrospinal fluid analysis and electrodiagnostic tests did not reveal any clinically significant abnormalities. A definitive final diagnosis was not reached in any of the cats, but hypersensitivity dermatitis was suspected in two cases. A variety of medications was used alone or in combination, including gabapentin (n = 6), meloxicam (n = 4), antibiotics (n = 4), phenobarbital (n = 2), prednisolone (n = 2) and topiramate (n = 2); ciclosporin, clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each. Clinical improvement was achieved in six cases; in five cats complete remission of clinical signs was achieved with gabapentin alone (n = 2), a combination of gabapentin/ciclosporin/amitriptyline (n = 1), gabapentin/prednisolone/phenobarbital (n = 1) or gabapentin/topiramate/meloxicam (n = 1).
Relevance and novel information
This is the first retrospective study on a series of cats with FHS. The diagnostic work-up did not reveal any significant abnormalities of the central or peripheral nervous system; dermatological and behavioural problems could not be ruled out. We propose an integrated multidisciplinary diagnostic pathway to be used for the management of clinical cases and for future prospective studies.
Introduction
Feline hyperaesthesia syndrome (FHS) is a poorly understood disorder of cats characterised by a wide variety of clinical signs. This condition was first reported in 1980 and several names have been used since, including ‘apparent neuritis’, ‘atypical neurodermatitis’, ‘rolling skin syndrome’ or ‘twitchy cat disease’. 1 Despite the disparity of names used to describe this disorder, the reported clinical signs are reasonably consistent and include: tail chasing; biting or licking the lumbar area, flank, anal area or tail; and skin rippling and muscle spasms of the dorsal lumbar area, which may be spontaneous or elicited by a light touch. Other clinical signs such as excessive and unusual vocalisations, episodes of apparently wild and uncontrolled jumping and running, hallucination and behaviours that mimic signs of oestrus were described in the first report on this condition by Tuttle in 1980. 1
Although FHS has been described for almost 40 years its aetiology is still unknown; indeed, many clinicians consider FHS an umbrella term, covering a variety of conditions ranging from excessive skin twitching to mutilation associated with a variety of pathologies. 2 In fact, clinical signs consistent with FHS have been anecdotally reported in association with dermatological (eg, flea allergic or hypersensitivity dermatitis), behavioural (eg, compulsive disorder and displacement behaviour), orthopaedic (eg, trauma to tail) and neurological (primary epilepsy or secondary to encephalitis or brain tumours, spinal disease such as intervertebral disc disease, neoplasia or infectious myelitis) conditions.2,3
In the most severe form, cats with clinical signs of FHS can severely damage or even mutilate their tails, requiring immediate medical assistance.2,4 Treatment with several medications with different indications, such as antiepileptic drugs (eg, phenobarbital, diazepam), anti-inflammatory drugs (eg, prednisolone), adjuvant analgesics (eg, gabapentin), behaviour-modifying medications (eg, lorazepam, oxazepam, buspirone, amitriptyline, fluoxetine, paroxetine or clomipramine), a synthetic progestin (megestrol acetate), and vitamins and other supplements (acetyl-L-carnitine, coenzymes, riboflavin, vitamin E) has been proposed; however, to date, we are not aware of any scientific study reporting results of these treatments in cats with clinical signs of FHS.1–5
The aims of this retrospective study were to report the results of diagnostic investigation and treatment in cats presenting with clinical signs associated with FHS (ie, skin twitching, vocalisation and/or over-grooming/mutilating of the tail without apparent inciting cause) and formulate an integrated multidisciplinary diagnostic approach to be used for the management of clinical cases and for future prospective studies.
Case series description
The electronic databases of two referral veterinary centres were retrospectively searched for information on signalment, history, clinical presentation, diagnostic work-up and treatment of cats with clinical signs compatible with FHS. 1 Inclusion criteria were a history of attacking or over-grooming the tail causing soft tissue damage associated with either vocalisation and/or lumbar hyperaesthesia, manifested as rippling of the lumbar skin occurring spontaneously or induced by gentle touch. Videos (see Video 1 in the supplementary material) were also evaluated when available.
Seven cats met the criteria and were included in the study; information on signalment and clinical presentation are summarised in Table 1. All seven cats were domestic shorthair; six were male and one was female, with two male cats entire and the other five cats neutered. The median age of presentation was 1 year (range 1–7 years). Two cats were indoor only. Episodes of tail chasing causing superficial soft tissue trauma were reported in all cats as per the inclusion criteria, and in some cats the damage was deeper (ie, mutilation) leading to removal of a conspicuous part of the tail in 4/7 cats (Figure 1 and Video 1 in the supplementary material). These episodes occurred multiple times per day in five cats, multiple times per week in one cat and the frequency was not reported for one cat. Vocalisation during the episodes was reported in five cats and rippling of the dorsal lumbar skin occurring spontaneously or induced by gentle touch was reported in 5/7 cats.
Signalment, clinical signs, treatment and follow-up in seven cats with feline hyperaesthesia syndrome with tail mutilation
Frequency of episodes of self-trauma and vocalisation: +++ = daily; ++ = weekly; + = monthly or occasional
MN = male neutered; DSH = domestic shorthair; AT = attacking or over-grooming the tail, flank, lumbar or perineal area; ST = soft tissue damage; M = mutilation; V = vocalisation; CBC = complete blood count; FeLV = feline leukaemia virus; FIV = feline immunodeficiency virus; ME = male entire; LH = lumbar hyperaesthesia (skin rippling and/or muscle spasms); CSF = cerebrospinal fluid; EMG = electromyogram; NA = not available; FN = female neutered
Self-mutilation of the tail in one of the affected cats (cat 6 in Table 1)
In addition to the clinical signs described above, three cats presented with dermatological signs, including dandruff, alopecia and erythema; two of these cats also had a history of intermittent gastrointestinal signs (vomiting and diarrhoea). One cat had a prior history of unacceptable urination of suspected behavioural aetiology. All cats received a complete physical and neurological examination, which did not reveal any other abnormalities.
Results of haematology and biochemistry were available for all cats and were unremarkable. Serology for Toxoplasma gondii and feline immunodeficiency virus (FIV)/feline leukaemia virus (FeLV) was performed in five and six cats, respectively. Mildly positive IgG titres for T gondii (1:100, normal ⩽1:50) with negative IgM titres were found in two cats, suggesting previous exposure to the agent. FIV and FeLV serology was negative. Five cats had MRI scans of the skull and vertebral column, including caudal vertebrae, and cerebrospinal fluid (CSF) analysis (total cell count, cytology and protein concentration) was performed in three cats. No significant abnormalities were detected in any of the cats with either diagnostic procedure.
Four cats underwent electrodiagnostic tests, including electromyography of the muscles of the pelvic limbs and tail (in all four cats), and motor nerve conduction studies of the sciatic-tibial nerves (two cats). The electrodiagnostic studies were normal with the exception of prolonged insertional activity and mild spontaneous activity detected in the muscles of the tip of the tail in two cats; both cats had mutilated the tip of their tail and therefore these mild abnormalities could have been associated with recent muscle trauma and were considered of unknown clinical significance.
Dermatological tests were performed in two cats with clinical signs suggestive of a dermatological condition. The tests included cytology of skin lesions and coat brushing and intradermal testing for environmental allergens (negative) in one cat and a serological test for detection of IgE antibodies to flea antigens (negative) in another cat. Four cats received regular flea treatment, one indoor-only cat did not receive any flea preventative and the information was not available for two cats.
A definitive final diagnosis was not reached in any of the cats. Hypersensitivity dermatitis was suspected in two cases, but it could not be proven as the diagnostic work-up for this condition was performed elsewhere and detailed information was not available.
A variety of medications were used alone or in combination to treat the clinical signs prior or after referral, including gabapentin (six cats), meloxicam (four cats), antibiotics (four cats), phenobarbital (two cats), prednisolone (two cats) and topiramate (two cats). Ciclosporin, clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each. In two cats with gastrointestinal and dermatological problems an exclusion diet was also attempted, but the dietary trial failed owing to poor owner compliance. Four cats received a combination of two or more medications, whereas three cats showed improvement with monotherapy.
Clinical improvement was achieved in six cases; in five cats remission of the clinical signs was achieved with gabapentin alone (two cats) or a combination of gabapentin/ciclosporin/amitriptyline (one cat), gabapentin/prednisolone/phenobarbital (one cat) or gabapentin/topiramate/meloxicam (one cat). Two of these cats with severe clinical signs (cases 2 and 6) had a recurrence of clinical signs approximately 2 years from remission after all medications had been briefly interrupted (case 2) or the topiramate dose tapered (case 6); another case was lost to follow-up during the slow tapering of prednisolone (see Table 1). One cat had a reduction in frequency of the episodes following treatment with clomipramine alone (see Table 1).
A diagnostic pathway for FHS (shown as a flow diagram in Figure 2) was created based on the information collected with this study and the combined experience of specialists in neurology, dermatology and behavioural medicine.
Flow diagram of proposed diagnostic pathways for feline hyperaesthesia syndrome (FHS). CBC = complete blood count; UA = urinalysis; EMG = electromyogram; CK = creatine kinase; FIV = feline immunodeficiency virus; FeLV = feline leukaemia virus; CSF = cerebrospinal fluid
Discussion
This retrospective study is, to our knowledge, the first to report the results of the diagnostic work-up and treatment of cats with clinical signs of FHS. The main limitations of this study are its retrospective nature and the limited number of cases included. The definition of FHS is still controversial as some authors consider mutilation of the tail part of the clinical presentation of FHS, 5 whereas others consider tail mutilation a different entity associated with neuropathic pain, possibly secondary to prior trauma to the tail and/or caudectomy. 6 To address this controversy, we decided to include in this retrospective case series only cats with clinical signs associated with the classical form of FHS, such lumbar hyperaesthesia, rippling skin, vocalisation and episodes of attacking or over-grooming the tail causing soft tissue damage or mutilation. Self-trauma to the tail was chosen as an inclusion criterion as in our experience this represents the most debilitating clinical sign that may lead to referral and/or recurrence of clinical signs after partial caudectomy. 7
FHS is a debilitating condition, especially in the most severe cases with mutilation of the tail. However, there is a tendency to treat FHS with a series of therapeutic trials prior to referral, including surgical removal of the injured part and/or a variety of medications. This reluctance to refer cases of FHS is not unexpected, considering the fact that the aetiopathology and organ systems involved in the development of this constellation of clinical signs remain unclear 38 years after the first report. 1
Ciribassi suggested that FHS is a behavioural displacement disorder, in which the cat develops high motivation for two or more conflicting behaviours (eg, eating or escaping another cat) that might lead to a species-appropriate but unrelated behaviour such as grooming. If this conflicting situation persists for a prolonged period of time the cat may manifest displacement behaviour, even when the competing motivations are not present, leading to a compulsive behaviour. 3 Based on this premise, signs of FHS should diminish and/or disappear after initiation of behaviour modification and/or treatment with psychoactive medications such as selective serotonin reuptake inhibitors (SSRIs; eg, fluoxetine) or tricyclic antidepressants (eg, clomipramine or amitriptyline), and glutamate-modulating medications (eg, topiramate and gabapentin) (see Figure 2).3,8 Although in some cases this therapeutic approach might be satisfactory, in our study 2/4 cats achieved remission of clinical signs only after anti-inflammatory or immunosuppressive medications were added to psychotropic drugs.
Some authors have suggested that the episodes of wild and uncontrolled jumping and running, tail chasing and vocalisation seen in FHS cats are a manifestation of epileptic activity.9,10 The partial response to treatment with antiepileptic drugs (AEDs) such as phenobarbital, gabapentin or topiramate, and the fact that some owners reported that cats with FHS appeared to be dazed and their pupils dilated during or immediately before the episodes, seem to support the theory of focal epileptic seizures.
An extensive neurological work-up, including neurological examination, haematology, biochemistry, MRI of the central nervous system, evaluation of peripheral nerves and muscles with electrodiagnostic tests, CSF analysis and serology for T gondii, FeLV and FIV, was performed in three cats in our study and a more limited work-up, including blood work and MRI, was performed in two additional cats without evidence of intra- or extracranial causes of seizures. These findings do not rule out the possibility that FHS could be an idiopathic form of epilepsy characterised by focal seizures, but the results of the diagnostic work-up and the incomplete response to treatment with AEDs cast doubt on this hypothesis.
Furthermore, the rippling or rolling of the skin over the lumbar spine occurring spontaneously or in response to gentle touch conforms to the definition of allodynia and/or alloknesis, which are abnormal sensory states wherein normally innocuous stimuli elicit unpleasant sensations or aversive responses (eg, pain or itch).6,11 The response of some cases of FHS to treatment with gabapentin and topiramate may support the presence of neuropathic itch or pain, as these AEDs have been successfully used for the treatment of neuropathic itch and pain in humans and veterinary patients, including cats.6,12,13
Gabapentin is a structural analogue of gamma-aminobutyric acid (GABA) neurotransmitter that was originally designed as an anticonvulsant, but has been found to be more effective in the treatment of neuropathic pain and anxiety in humans and companion animals.14,15 Gabapentin is reported to be a safe medication, the suggested initial dosage for analgesia is 3 mg/kg PO q24h titrated upwards to 5–10 mg/kg PO q8–12h as needed; mild side effects are reported, including sedation and ataxia. 16 Topiramate is a glutamate-modulating anticonvulsant medication with a reportedly complex mechanism of action, including blockage of voltage-dependent Na+ channels and potentiation of GABAA neurotransmission, and inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptor facilitation of Ca2+ influx. 17 In addition to anticonvulsant properties, there are reports of a potential beneficial effect of topiramate in the treatment of obsessive-compulsive disorders and self-mutilation in humans and idiopathic ulcerative dermatitis in a cat.12,17,18
Grant and Rusbridge reported that a 2-year-old domestic shorthair cat diagnosed with idiopathic ulcerative dermatitis and self-trauma to the skin of the neck showed a significant improvement within 2 weeks of initiating treatment with topiramate (Topamax; Janssen-Cilag), 5 mg/kg PO q12h; this after treatment with gabapentin 10 mg/kg PO q12h, pregabalin (Lyrica; Pfizer) 5 mg/kg PO q12h and phenobarbital 12.5 mg PO q12h for 4 weeks each failed to improve the clinical signs. 12 During a 30 month follow-up the clinical signs were controlled by topiramate, with the exception of two recurrences following two attempts to stop this medication. No significant side effects were reported in the cat in this case report; however, sedation and inappetence have been noted in cats treated with topiramate for refractory epilepsy.12,16
A definitive final diagnosis was not reached in any of the cats in our study, although hypersensitivity dermatitis was suspected in two cats. This is consistent with earlier anecdotal reports suggesting that dermatological diseases may be involved in the pathogenesis of FHS.1,2 Owing to the retrospective nature of this study and the fact that the cats were referred after dermatological conditions were ruled out by the primary veterinarian, specific history and detailed information on the dermatological work-up were missing. A full dermatological history and investigation is important as, unlike dogs, clinical signs are not specific for any particular hypersensitivity dermatoses or other causes of itch. 19 Thorough parasite control should be used to eliminate fleas, even in indoor cats. 20
Drugs with known efficacy in feline hypersensitivity disorders include prednisolone or methylprednisolone (1–2 mg/kg PO q24h to remission and taper), ciclosporin (Atopica Cat; Elanco Animal Health [7 mg/kg PO q24h to remission and taper]) and oclacitinib (Apoquel; Zoetis [0.6–1.0 mg/kg PO q12h to remission and then q24h]).13,21 In dogs, oclacitinib acts on Janus kinase (JAK)-1 and JAK-2 receptors involved in cell signalling pathways activated by various cytokines and could potentially cause bone marrow suppression when used at high dosages over a long period of time. 13 There is little information available on the potential immunosuppressive effects of oclacitinib in cats; Ortalda et al treated 12 cats with hypersensitivity dermatitis (>12 months of age and >3 kg body weight) for 28 days and did not observe any adverse effects; however, they selected cats with negative FIV and FeLV status and without exposure to raw meat to reduce the risk of toxoplasmosis. 13 The authors of this small pilot study on the use of oclacitinib in cats advised monitoring blood cells count on a regular basis when using oclacitinib at dosages >1.0 mg/kg PO q12h. 13
Therapeutic trials with corticosteroids, ciclosporin or oclacitinib may help eliminate cats with hypersensitivity dermatitis and/or control itch and inflammation where this is a component of FHS (see Figure 2).
Similarly, we do not have access to information that will allow us to rule out the possibility of a behavioural problem, even in cases in which a prior behavioural problem was suspected (see case 3 in Table 1). Ideally, cases of FHS should be referred to a specialist in behaviour; when this is not possible, a detailed behavioural history should be collected to identify factors predisposing to anxiety, fear, over-attachment to owner (eg, adoption from humane shelter, arrival of new pets in the house and multi-cat household tension; see Figure 2). Then, if a behavioural disorder is suspected, attempts to reduce detrimental physiological stress and optimise the emotional state, and physical and social environment should be made prior to, or in conjunction with, therapeutic trials with tricyclic antidepressants (TCAs), such as clomipramine or amitriptyline (the recommended dosage for both medications is 0.5–1.0 mg/kg PO q24h and should be gradually increased and gradually discontinued), or SSRIs, such as fluoxetine (0.5– 2.0 mg/kg PO q24h dosages should be gradually increased and gradually discontinued).3,16
The main side effects of TCAs in cats are sedation, diarrhoea, anticholinergic effects (eg, dry mouth, mydriasis, urine retention, constipation).3,16 Potentiation of arrhythmias (due to the anticholinergic effects) in predisposed patients, lowering of seizure threshold and elevation of liver enzymes may also occur; some clinicians recommend measuring liver enzymes prior to therapy, 1 month after initial therapy and yearly thereafter.3,16 TCAs should be used with caution in association with other central nervous system depressants such as SSRIs and AEDs. 16 Clomipramine is licensed for the treatment of compulsive and anxiety disorders of dogs and cats in various countries (including the USA and the UK), it is the most selective inhibitor of serotonin uptake of all of the TCAs, with similar indications and application of SSRIs, and is preferred to other TCAs such as amitriptyline for its better anti-compulsive action and palatability. 22
SSRIs, such as fluoxetine, have been advocated for the treatment of urine spraying and compulsive disorders of cats. The onset of action for SSRIs is similar to that of TCAs, with the onset of effect 3–4 weeks from the start of treatment; however, for the treatment of compulsive disorders the effect may not be seen for as long as 8 weeks. 23 The exact time for improvement could not be evaluated in our study and it is possible that the short duration of treatment may have affected the outcome of treatment with fluoxetine in case 4 (see Table 1). SSRIs inhibit the function of the liver cytochrome P450 enzymes; therefore, caution should be used when administered concurrently with other medications that rely on these enzymes for their metabolism, in particular phenobarbital, benzodiazepines and TCAs.3,16 SSRIs should not be used in combination with each other or with other drugs that increase serotonin levels, such as TCAs.3,16 The main side effects of SSRIs in cats are behaviour changes (anxiety, irritability and sleep disturbances), anorexia, diarrhoea and changes in elimination patterns.3,16
Another limitation of this study, in addition to its retrospective nature and limited number of cases, is that none of the cats had a complete assessment and diagnostic work-up performed by specialists in behaviour, dermatology and neurology. Referral to a clinical behaviourist was strongly recommended for four cats and referral to a dermatologist was recommended for the other three cats; in four cases the owners declined a tertiary referral owing to financial limitations and three cats were lost to follow-up. This highlights the need for a systematic and comprehensive approach to the diagnosis of FHS.
Conclusions
In this study we retrospectively collected and analysed information on seven cats with clinical signs of FHS, including self-trauma to the tail. A definitive diagnosis for this complex constellation of clinical signs is still elusive and it is difficult to draw conclusions regarding the ideal therapy. Based on the information derived from this study and a review of the available literature we formulated a diagnostic pathway for FHS and created a flow diagram for easy interpretation (Figure 2). This diagnostic pathway needs to be validated by its application on a larger number of cases, but it is the first step towards a standardised approach to this condition and forms the basis for prospective studies.
Footnotes
Supplementary material
Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
References
Supplementary Material
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