Idiopathic generalised tremor syndrome in two cats

Abstract

Two male neutered domestic shorthair cats were evaluated for generalised tremors. On neurological examination both cats showed whole-body tremors, worsening with stress. A mainly cerebellar disorder was suspected. Blood examination, cerebrospinal fluid analysis and electrophysiological examination of both cats and magnetic resonance imaging of the brain in one cat were normal. Idiopathic generalised tremor syndrome (IGTS) was suspected owing to the exclusion of underlying causes and the clinical similarities with the syndrome in dogs. Treatment as recommended for dogs was initiated and resulted in improvement. This report describes the first cases of IGTS in cats.

Case Report

Idiopathic generalised tremor syndrome (IGTS) is a cerebellar disease in dogs, that was often described as little white shaker syndrome because it occurred initially in small white dogs.^1,2 The underlying aetiology remains unknown, but an autoimmune inflammation of the cerebellum associated with an imbalance in neurotransmitters is suspected. ³ To our knowledge, this is the first report of suspected feline IGTS.

A 10-month-old male neutered domestic shorthair cat was presented with generalised tremors and ataxia. These signs first occurred 2 weeks before presentation, progressed over 4 days and then remained stable. Because the tremors worsened with target-directed movement, the cat was unable to eat without help. The cat lived strictly indoors, did not have access to toxic substances and had a predominantly white coat. Vaccinations against feline panleukopenia virus, feline viral rhinotracheitis and calicivirus were performed regularly, with the last vaccination 7 months prior to onset of the tremor. The cat was on a commercial feline diet and did not receive any medication in the 4 weeks before onset of the tremor.

Physical examination was unremarkable. On neurological examination continuous severe whole-body intention tremors, which worsened with excitement and ataxia, on all limbs was detected. Menace responses were absent bilaterally with preserved vision. A mainly cerebellar localisation was suspected. Important differential diagnoses included degenerative, inflammatory, toxic and neoplastic diseases.

Complete blood count (CBC) and serum biochemistry, including electrolytes, revealed a mild leukocytosis (11.8 × 10⁹/l; reference interval 7.5–9 × 10⁹/l). An antigen enzyme-linked immunosorbent assay (ELISA) for feline leukaemia virus (FeLV), and serology for Toxoplasma gondii and feline immunodeficiency virus (FIV) were negative.

A 0.2-Tesla magnetic resonance imaging (MRI) study of the brain was performed, including sagittal and transverse T1-weighted and T2-weighted images, dorsal T2-weighted images, and sagittal and transverse post-gadolinium-contrast T1-weighted images, as well as transverse fluid-attenuated inversion recovery images; no abnormalities were detected.

Cisternal cerebrospinal fluid (CSF) was collected and contained a normal cell count and protein level. Polymerase chain reaction (PCR) on the CSF for Borna virus, coronavirus and T gondii were negative.

Owing to the clinical similarity with canine shaker disease and the exclusion of underlying causes, IGTS was suspected. To exclude neuromuscular disorders, which can potentially also cause tremors, electrophysiological examination, including electromyography, motor nerve conduction velocity and repetitive nerve stimulation, was performed and revealed no abnormalities.

Diagnostic therapy for IGTS with prednisolone and diazepam was initiated. Owing to the severity of signs, the cat was hospitalised. Diazepam was given intravenously (1 mg/kg q8h) and prednisolone was administered subcutaneously (2 mg/kg q24h). The cat improved, showing only mild intention tremors and ataxia, and was able to eat 2 days after initiation of treatment. The cat was discharged and oral medication (Table 1) was continued.

Table 1.

Treatment protocol

Treatment week	Prednisolone	Diazepam
1–2	2 mg/kg PO q24h	1 mg/kg PO q8h
3–4	1 mg/kg PO q24h	1 mg/kg PO q12h
5–6	0.5 mg/kg q24h	1 mg/kg PO q24h
7–8	0.5 mg/kg q48h	–

Four weeks later, physical and neurological examination did not reveal any abnormalities. CBC and serum biochemistry were within normal limits.

Three weeks later, while tapering the medication, the cat relapsed, showing mild generalised tremors. Prednisolone was increased from 0.5 mg/kg every other day to 1 mg/kg once daily. All signs resolved within days, except for mild intention tremors of the head. Prednisolone was tapered every 4 weeks and the owner declined to stop the medication. Therefore, the cat remains on prednisolone (0.5 mg/kg) every other day without side effects.

On examination 3 months after diagnosis the cat showed very mild intention tremors and no other abnormalities. According to the owners, the tremors disappeared 6 months after initiation of treatment and remained absent until the last follow-up telephone contact 14 months after diagnosis.

A 17-month-old male neutered domestic shorthair cat was presented with a 4-week history of generalised tremors and an uncoordinated gait. The signs progressed initially over 1 week and then remained stable. Because the tremors worsened with target-directed movement, the cat had difficulty eating. The cat lived strictly indoors, did not have access to toxic substances and had a completely white coat.

Vaccinations against feline panleukopenia virus, feline viral rhinotracheitis and calicivirus were performed regularly with the last vaccination 3 months prior to onset of signs. The cat was on a commercial feline diet and had not received any medication in the 4 weeks prior to development of clinical signs.

Physical examination was unremarkable. On neurological examination the cat showed continuous, severe, whole-body tremors, which worsened with excitement, and a mild ataxia on all four limbs.

A mainly cerebellar localisation was suspected with the same differential diagnoses as listed for case 1.

CBC and serum biochemistry, including electrolytes, were within normal limits. MRI of the brain was declined by the owner. Cisternal CSF (cell count and protein level) revealed no abnormalities. Electrophysiological examination was performed and revealed no abnormalities.

Despite the lack of brain imaging, the cat was highly suspected of having IGTS owing to the clinical similarity with its canine counterpart. A diagnostic treatment was initiated (Table 1). According to the owners, the cat improved after 2 days and was normal 1 week later. The medication was stopped after 8 weeks and the cat remains without clinical signs until the last telephone contact with the owners 14 months after diagnosis.

Shaker disease is a well-known syndrome in dogs, that has also been described as little white shaker syndrome ⁴ and idiopathic cerebellitis. ⁵ As the disease has now been described in dogs with different coat colours, shaker disease or shaker dog syndrome seems more appropriate.^6–8 Because the underlying pathology is not known in cats and might differ from the cause in dogs, the term IGTS is used to describe these feline cases. The role of coat colour remains doubtful in dogs and, interestingly, a lot of white coat was present in both cats. Whether this is just a coincidence or reflects an association of the disease with coat colour in cats remains to be elucidated.

In dogs, the disease often starts at a young age (<5 years), as was the case in our cats.^8–10 Clinical signs seen in these cats seem very similar to signs of shaker disease in dogs with whole-body tremors, often worsening with excitement. The whole-body tremor is not only a cerebellar sign, but can also represent a generalised central nervous system disorder. In dogs, other signs of cerebellar dysfunction, such as lack of menace responses, nystagmus, ataxia and head tilt, have been described. ¹ In one study of seven dogs, tremors occurred in all dogs, but only five had absent menace responses or nystagmus. Ataxia occurred in four dogs and head tilt in three. The progression of signs ranged between 2 days and 6 weeks. ¹ In another study with 90 dogs, 93% of the dogs showed generalised tremors and 7% localised tremors. Gait abnormalities, such as ataxia or hypermetria, occurred in 73% of the dogs in this study, but only 28% had a reduced menace response. ⁸ In both cats in this study tremors and ataxia were seen, but only one cat showed absent menace responses. The progression of signs was similar to the canine cases.

The exact aetiology in dogs remains unclear. Based on histopathological abnormalities in some cases, an acquired autoimmune inflammation of the cerebellum has been suspected. ² As both cats are still alive, histopathology is lacking. Although an inflammatory aetiology is suspected, only 3/7 dogs in one report had elevated white blood cell counts, and only 5/7 dogs had elevated protein in their CSF. ¹ Both cats presented here had normal CSF findings.

Infectious agents that cause tremors in cats include T gondii, feline coronavirus, Cryptococcus neoformans, Borna virus, FeLV and FIV. Toxoplasma gondii, feline coronavirus and Borna virus were excluded in cat 1 using PCR on a CSF sample, and FeLV and FIV were excluded using ELISA on a blood sample. On the MRI of the brain of cat 1 no abnormalities were detected, which excludes a cryptococcal- or coronavirus-associated lesion and secondary neoplastic lesion due to FeLV.

The most important tremorgenic toxins in cats are permethrin, organosphosphates and carbamates, although a large variety of toxins can cause tremors in cats. ¹¹ Considering the clinical history, intoxications were considered unlikely in both cats, therefore cholinesterase activity was not measured.

In dogs, the diagnosis is based on typical signs, exclusion of other causes and treatment response. Also, in both cats, the diagnosis was based on the similarity to canine shaker disease and the exclusion of other causes. Unfortunately, in the second cat, MRI of the brain and infectious screening was not performed, but with the excellent treatment response, other underlying diseases seem very unlikely.

As an autoimmune aetiology is suspected, treatment in dogs consists of immunosuppressive dosages of corticosteroids, sometimes in combination with diazepam, to relieve the severity of the tremors. Most dogs improve within days after initiation of treatment and the treatment can often be discontinued after 1–3 months. However, some dogs require lifelong treatment to prevent relapses. The same treatment was given to both cats leading to a similar rapid improvement. One cat had a relapse and remains on a low-dose corticosteroid treatment. Oral diazepam has been associated with an idiosyncratic hepatic toxicity in cats. Therefore, the liver function of the cats was monitored and no abnormalities were seen. Owing to this potential risk it can be discussed whether diazepam should only be added in severe feline cases.

The prognosis of shaker disease in dogs is good, and seems to be good in these suspected feline cases. When, in the future, more cases of feline shaker disease are detected, more information about the prognosis will be available. Also, it would be interesting to confirm the diagnosis histopathologically in cases where the owners decline treatment.

Conclusions

To our knowledge this report describes the first cases of suspected feline IGTS. It should be considered as a differential diagnosis in cats with whole-body tremors with or without other cerebellar signs. As this syndrome is an idiopathic disease, all other possible causes of generalised tremors should be excluded before a diagnostic treatment is initiated.