Introduction
Methods
Level of evidence [7] | |
I | Evidence obtained from a systematic review of all relevant randomised controlled trials. |
II | Evidence obtained from at least one randomised controlled trial. |
III-a | Evidence obtained from one or more controlled trials, pseudo-randomised by alternate allocation, birth date or other planned method. |
III-b | Evidence obtained from prospective or retrospective cohort studies with concurrent controls, case-control studies, or interrupted time-series with a control group. |
III-c | Evidence obtained from cohort studies with historical controls, two or more single-arm studies, or interrupted time-series without a parallel control group. |
IV | Evidence comprises opinions based on clinical experience, descriptive studies or reports by clinical bodies or committees. |
Grading of recommendations [8] | |
A | Body of evidence can be trusted to guide practice; includes one or more level I studies, or several at level II directly applicable to the target population, and demonstrating overall consistency of results. |
B | Body of evidence can be trusted to guide practice in most situations; includes one or two studies rated as level II or several level III studies, directly applicable to the target population, and demonstrating overall consistency of results. |
C | Body of evidence provides some support for recommendation(s) but care should be taken in its application; includes studies rated as III-c, or level I or II with a moderate risk of bias, some inconsistency and applicable to target population with caveats. Population studied is not the target population, however, it would make sense clinically to apply this evidence to target population. |
D | Body of evidence is weak and recommendation must be applied with caution; includes level IV, or level I to IV studies with high risk of bias, inconsistent evidence and that are not applicable to target population. |
GPP | Good practice point: Recommended best practice based on clinical experience and expert opinion. |
Results
Diagnosis
Primary care | U&Es Creatinine FBC ESR/CRP | Liver enzymes γ-GT TFT Vitamin B12 | Folate Glucose CXR |
Secondary care (first line) | αFP Blood film Caeruloplasmin/copper Coeliac screen Creatine kinase Genetic tests for FRDA, SCA 1, 2, 3, 6, 7 (12, 17) and FXTAS | Lactate Lipid-adjusted vitamin E and lipoproteins Lumbar puncture (cells, protein, glucose, cytology, oligoclonal bands, lactate, ferritin) MRI brain and cervical spine | Anti-Hu/Yo and other paraneoplastic antibodies Anti-GAD Anti-VGCC CT (chest, abdomen, pelvis) 14–3-3 and other proteins in CSF (prion diseases) |
Secondary care (second line) | Cholestanol Plasma oxysterols Bile acids Coenzyme Q10(ubiquinone) Electroencephalography Very long chain fatty acids | Muscle biopsy Ophthalmology/OCT Peripheral nerve conduction studies Phytanic acid | Remaining genetic tests (NGS) Total body PET scan White cell enzymes |
Recommendations | Grade |
---|---|
The clinical context (speed of evolution, episodic/fluctuating versus progressive etc.) should determine the investigation of individual cases. | GPP |
Ataxia in adults can arise due to serious neurological disease and urgent referral for secondary care (to a neurologist) should be made without delay following primary care investigation. | GPP |
Children presenting with ataxic symptoms should be referred urgently for paediatric assessment (usually by local specialists, who may liaise with paediatric neurologists, clinical geneticists, etc). | GPP |
Rapid progression (over weeks or months) can denote a paraneoplastic cause, prion disease or multiple system atrophy, thus urgent investigations are required. | GPP |
When a diagnosis of progressive ataxia is made referral to a Specialist Ataxia Centre is encouraged. | GPP |
Neurologists should liaise with their clinical genetics counterparts given the potential implication for family members of patients who undergo genetic testing. | GPP |
Informed consent should be sought from all those undergoing genetic testing. | GPP |
It is essential to offer genetic counselling to patients and discuss the implications of a genetic test prior to testing. | GPP |
Genetic counselling should include the implications of having a genetic test for the individual and their family and any reproductive choices they may make. | GPP |
Asymptomatic ‘at risk’ subjects should be offered genetic counselling. | GPP |
Genetic testing of asymptomatic ‘at-risk’ minors is not generally recommended, but should be considered on a case-by-case basis. | GPP |
Any genetic test results from research studies need to be validated by an accredited laboratory before a formal result is given to the patient. | GPP |
Medical interventions
4.1 Spasticity | |
Recommendation | Grade |
Careful assessment by a neurologist, with advice from a physiotherapist, is required to decide on the type of treatment of spasticity. | GPP |
Consider physiotherapy first to treat spasticity, and if that does not provide complete benefit use pharmacological treatment. Surgery should be considered in cases where physiotherapy and pharmacological treatments have not worked. | GPP |
For pharmacological treatment of generalised spasticity consider using the following oral medications (usually in this order due to the profile of side effects and better tolerability): baclofen, tizanidine, gabapentin, clonazepam, dantrolene sodium or diazepam. | GPP |
To treat focal spasticity refer to a specialised clinic for treatment with intramuscular botulinum toxin injections, followed by physiotherapy. | GPP |
4.2 Tremor | |
Recommendation | Grade |
Patients with ataxia who have tremors should be offered pharmacological treatment using Propranolol, Primidone, Propranolol and Primidone in combination, Topiramate, Clonazepam and Gabapentin (in this order). | GPP |
In patients where tremor is extremely debilitating and not responsive to medication a referral to a centre specialising in functional neurosurgery should be considered. | |
4.3 Dystonia | |
Recommendation | Grade |
Focal dystonia should be treated with botulinum toxin injections. | GPP |
Generalised dystonia should be treated with oral medications, followed by surgery if this is not effective. | GPP |
Patients with dystonic tremor should be offered physiotherapy and oral medications followed by surgery if the former are ineffective. | GPP |
4.4 Scoliosis | |
Recommendation | Grade |
Regular surveillance of the development of scoliosis in FRDA patients (especially children) is recommended as it is important for it to be treated. | GPP |
If scoliosis is detected, referral to a physiotherapist and spinal surgeon is recommended. | GPP |
For mild scoliosis the patient should be kept under close observation and the spinal surgeon should consider treatment with bracing. | |
For severe scoliosis consider surgery to straighten the spine. | |
Regular follow-up by a spinal surgeon is recommended after an operation on the spine. | |
4.5 Pain | |
Recommendation | Grade |
Treat pain with physiotherapy and/or pharmacological treatments. | GPP |
Consider use of the following drugs to treat neuropathic pain: Amitriptyline, Nortriptyline, Carbamazipine, Pregabalin, Gabapentin and Duloxetine. | GPP |
Consider referral to a pain management clinic if pain is severe or limiting daily activities. | GPP |
4.6 Cardiac involvement in FRDA | |
Recommendation | Grade |
When FRDA is diagnosed a referral to a cardiologist is recommended for the early diagnosis of cardiac problems and the management of cardiac complications, where required. | GPP |
Regular screening by a cardiologist is recommended in FRDA patients; once every two years before any cardiac disease is documented, and at least annually after manifesting features of asymptomatic cardiac disease. | GPP |
Transthoracic Echocardiography and ECG should be used for the diagnosis and monitoring of the myocardial changes. | GPP |
Holter monitoring should be undertaken to detect silent cardiac arrhythmias or the association of symptoms (such as palpitations, shortness of breath) with the underlying rhythm. | GPP |
A cardiologist should consider pharmacological treatment (including the use of anticoagulants), and in some cases the implantation of pacing devices, in collaboration with the neurologist. | GPP |
4.7 Bladder problems - lower urinary tract dysfunction | |
Recommendation | Grade |
In primary care, test for urinary tract infection and measure post-void residual (to exclude common causes of urgency and frequency). If these are normal, check for other common causes such as prostate enlargement. | GPP |
Practical advice should be given about cutting down caffeine, fizzy drinks and alcohol, as well as information about timed voiding and bladder retraining whenever appropriate. The fluid intake should be individualized; a fluid intake of between 1 to 2 L a day is recommended (taking into consideration possible concurrent cardiac issues). | GPP |
Advice on pelvic floor exercises should be given as it may be helpful especially when symptoms are mild. | GPP |
Most individuals with overactive bladder symptoms will require antimuscarinic medications (such as tolterodine, oxybutynin, propiverine and solifenacin). | GPP |
In patients with cardiac complications and/or cognitive problems caution is advised when using antimuscarinic medications. | GPP |
In patients with cognitive problems, more selectively-acting antimuscarinic medications, such as trospium chloride or darifenacin should be considered. | GPP |
In some instances, referral to an urologist is recommended eg: in cases of haematuria or suspicion of concomitant urological condition. | GPP |
4.8 Gastroenterological problems | |
Recommendation | Grade |
Suggest changes in lifestyle (eg: diet, fluid and mobility assistance) for patients with constipation, followed by the use of laxatives or suppositories. | GPP |
Consider referral for specialist assessment if patients have urgency and faecal incontinence. | GPP |
4.9 Sexual dysfunction | |
Recommendation | Grade |
Consider discussing sexual function with male patients due to the potential for erectile dysfunction. | GPP |
Treat erectile dysfunction where appropriate with phosphodiesterase-5 inhibitors. Treatment decisions should balance the needs of the person and the potential side effect of medications e.g., hypotension. | GPP |
If patients have cardiac pathologies caution should be exercised when considering medication, and consultation with a cardiologist is recommended. | GPP |
4.10 Swallowing and dysphagia | |
Recommendation | Grade |
If patients show symptoms of dysphagia a referral to a speech and language therapist should be made (see Additional file 1: Table S2). | GPP |
If there is unintentional weight loss due to dysphagia consider the use of nutritional supplements and refer to a dietician. | GPP |
If calorie intake cannot be maintained despite supplements, discuss the possibility of a percutaneous gastronomy (PEG) to provide secure feeding. | GPP |
4.11 Sialorrhoea (excessive salivation) | |
Recommendation | Grade |
Sialorrhoea is normally associated with dysphagia, thus a referral to a speech and language therapist is recommended for assessment of swallow. | GPP |
Treat sialorrhoea and thick secretions according to Bavikatte et al. 2012 [9] (and the full guidelines). | GPP |
4.12 Audiology and hearing | |
Recommendation | Grade |
If a patient is experiencing hearing problems refer to Audiology services for a battery of hearing tests. | GPP |
A hearing aid trial should be considered although it is often not suitable for this patient population. | GPP |
A trial with an FM hearing device is recommended in cases of ataxia with Auditory Neuropathy Spectrum Disorder (ANSD). | |
Refer to hearing therapist or speech and language therapist for guidance on communication tactics. | GPP |
For those who do not achieve any benefit from hearing aids, consider a referral to a cochlear implant centre. | D [26] |
In specific cases (e.g. ANSD) a referral to a neuro-otologist should be considered. | GPP |
4.13 Eye symptoms | |
Recommendation | Grade |
A referral to a neuro-ophthalmologist is recommended if ataxia patients have any eye symptoms. | GPP |
If disabling nystagmus or oscillopsia is present treatment is recommended, often with either gabapentin or baclofen. | |
Refer to an optometrist or neuro-ophthalmologist for restoration of single vision with prisms in cases of diplopia. | GPP |
Patients with visual impairment should be offered low vision aids and the possibility of having their visual disability registered. | GPP |
4.14 Cognition | |
Recommendation | Grade |
When cognitive impairment is suspected (even if mild) referral to a Neuropsychology department is recommended. | GPP |
Cognitive rehabilitation is recommended for those patients with cognitive impairment. | C [30] |
Characterising the course of the cognitive impairment is advisable in order to inform the likely prognosis. | GPP |
GPP | |
4.15 Depression and other psychiatric symptoms | |
Recommendation | Grade |
In many cases depression can be treated in primary care using medications, counselling or cognitive behavioural therapy. | GPP |
In more severe or complex cases of depression and other psychiatric symptoms a referral to a psychiatrist/neuropsychiatrist in secondary care is recommended. | GPP |
For adults consult NICE Guidelines for the treatment of depression in patients with a chronic physical disorder [10]. | GPP |
4.16 Inherited episodic ataxias | |
Recommendation | Grade |
Advise episodic ataxia patients on identification and avoidance of common triggers that may cause attacks such as stress, caffeine and alcohol consumption, and excessive physical exertion. | GPP |
Acetozolamide is recommended as the first line drug in episodic ataxia types 1 and 2, although not all patients respond. | GPP |
Patients taking acetazolamide should be advised to keep hydrated to prevent the development of renal calculi and should undergo annual ultrasound screening of the urinary tract. | D |
Patients with a known hypersensitivity to sulponamides should be counselled at the start of treatment and need to be kept under surveillance. | GPP |
Consider use of 4-aminopyridine on a named patient basis as second line drug in episodic ataxia type 2 if acetazolamide is not beneficial. | C [31] |
In episodic ataxia type 1 consider use of carbamazepine, phenytoin or lamotrigine as second line treatment. | GPP |
Treatable ataxias
5.1 Gluten ataxia | |
Recommendation | Grade |
It is recommended that patients with idiopathic cerebellar ataxia are tested for gluten sensitivity. | GPP |
Consider testing for antibodies against TG6 (when possible) as a more sensitive test for gluten ataxia. | |
Ataxia patients with or without enteropathy who have serological evidence of gluten sensitivity should be advised to start a gluten-free diet without delay. | C [34] |
Patients who are starting a gluten-free diet should be advised about strict adherence and given dietetic advice. | GPP |
Close monitoring is recommended with six-monthly testing to ensure for elimination of antigliadin antibodies. | GPP |
5.2 Ataxia with vitamin E deficiency | |
Recommendation | Grade |
Patients diagnosed with ataxia with vitamin E deficiency or abetalipoproteinemia should be treated with vitamin E supplements. | |
5.3 Ataxia with vitamin B12 deficiency | |
Recommendation | Grade |
Patients diagnosed with ataxia and Vitamin B12 deficiency should be treated with Vitamin B12. | GPP |
5.4 Ataxia with CoQ10 (ubiquinone) deficiency | |
Recommendation | Grade |
Patients diagnosed with ataxia with CoQ10 deficiency should be treated with CoQ10 supplements. | |
Consider treatment of patients diagnosed with AOA1 with CoQ10 supplementation. | |
5.5 Cerebrotendinous xanthomatosis | |
Recommendation | Grade |
Prompt diagnosis of cerebrotendinous xanthomatosis is advised in order to initiate treatment. | GPP |
If cerebrotendinous xanthomatosis is diagnosed treatment with chenodeoxycholic acid is recommended. | |
5.6 Niemann-Pick type C (NPC) | |
Recommendation | Grade |
If NPC is suspected based on clinical investigations, perform diagnostic tests described above. Early diagnosis is important as it is a treatable condition. | GPP |
If NPC is diagnosed refer promptly to a Specialist Centre for treatment and management. | GPP |
Treatment with Miglustat is recommended in both adult and paediatric cases and is available in Specialist Centres. |
6.1 Glucose transporter 1 deficiency | |
Recommendation | Grade |
If Glut-1 DS is diagnosed treat with a ketogenic diet. | |
6.2 Hypobetalipoproteinaemia | |
Recommendations | Grade |
Consider management of the moderate form of hypobetalipoproteinemia by reducing the proportion of fat in the patient’s diet and vitamin E supplementation. | GPP |
6.3 Hartnup disease | |
Recommendation | Grade |
Consider treating Hartnup disease with nicotinamide or tryptophan-rich diet, and advise patients on a high protein diet, sunlight protection and avoidance of photosensitizing drugs. | GPP |
6.4 Biotinidase deficiency | |
Recommendation | Grade |
Treat patients diagnosed with biotinidase deficiency with biotin. | GPP |
6.5 Pyruvate deficiency | |
Recommendation | Grade |
Consider treatment with thiamine, carnitine or lipoic acid and advising on a ketogenic diet. | GPP |
6.6 Structural disorders | |
Recommendation | Grade |
If ataxia is due to structural causes a referral for neurosurgical treatment may be recommended. | GPP |