Imbalance and ataxia

Ataxia is incoordination of movement, gait or balance that is not explained by weakness. Imbalance is the symptom of unsteadiness. The cerebellum and its connections, proprioceptive input from the dorsal columns and peripheral nerves, and the vestibular system all contribute. The main clinical point is the tempo of onset: acute ataxia can be a posterior circulation stroke or posterior fossa haemorrhage, and CT head can miss early cerebellar infarction.

Anatomy. The cerebellar vermis controls trunk and gait; the hemispheres control ipsilateral limb coordination; the flocculonodular lobe controls eye movement and vestibular function. Sensory ataxia arises from loss of proprioception in the peripheral nerves, dorsal root ganglia or dorsal columns.

Classification by site. Cerebellar (vermian, hemispheric or pancerebellar), sensory, vestibular, frontal (gait apraxia), and mixed.

Classification by tempo. Acute (minutes to days), subacute (weeks to months), chronic progressive (months to years, including hereditary), and episodic.

Key distinctions. Cerebellar ataxia has a wide based gait, truncal sway, and limb incoordination that is not improved by vision. Sensory ataxia has a positive Romberg test, stamping gait, and loss of position and vibration sense; it worsens with eyes closed.

History. Tempo of onset, associated vertigo, headache, vomiting, neck pain, diplopia, dysarthria, dysphagia, limb clumsiness, sensory symptoms, bladder symptoms, falls, cognitive change and fluctuation. Ask about recent viral illness or vaccination, alcohol intake (quantity and duration), diet, bariatric surgery or malabsorption, weight loss, and cancer history. Ask about family history of ataxia, early onset disease, consanguinity, and pes cavus.

Drug and toxin history. Phenytoin, carbamazepine, lithium, benzodiazepines, amiodarone, cytarabine, platinum agents, metronidazole (prolonged use), isoniazid, solvents, heavy metals (lead, mercury, thallium).

Examination. Gait (wide based, staggering), tandem gait, truncal sway in sitting, finger to nose, heel to shin, dysdiadochokinesia, rebound, intention tremor, scanning dysarthria, gaze evoked nystagmus, saccadic intrusions, ocular movements (ophthalmoplegia), power, tone and reflexes (absent in neuropathy, brisk in myelopathy), sensation (vibration and proprioception), Romberg test, cognition, and skin and eye signs (telangiectasia, Kayser Fleischer rings).

In acute presentations with vertigo and nystagmus, use the HINTS examination only in continuous vestibular syndrome with spontaneous nystagmus, and only by examiners trained in it.

Red flags

• Acute onset, or sudden worsening
• Headache, vomiting, neck pain or reduced consciousness
• Inability to sit unsupported
• Ophthalmoplegia with confusion (Wernicke encephalopathy)
• New diplopia, dysphagia or facial numbness
• Papilloedema or fever
• Bladder dysfunction, sensory level, or limb weakness
• Weight loss, cancer history, or smoking history

Special groups. Children: acute cerebellitis (post-infectious), toxic ingestion, posterior fossa tumour, opsoclonus myoclonus with neuroblastoma. Pregnancy: Wernicke encephalopathy with hyperemesis. Region specific: tropical ataxic neuropathy associated with a cassava dominant diet, HIV and neurosyphilis.

Acute

• Cerebellar infarction (can present with isolated gait ataxia), cerebellar haemorrhage, vertebral artery dissection, basilar artery thrombosis
• Posterior fossa tumour or abscess, with acute hydrocephalus
• Acute cerebellitis
• Alcohol intoxication, drug toxicity (anticonvulsants, lithium, benzodiazepines)
• Wernicke encephalopathy
• Miller Fisher syndrome and Guillain Barré syndrome, Bickerstaff brainstem encephalitis
• Multiple sclerosis relapse
• Hypoglycaemia, hyperthermia
• Vestibular neuritis and vestibular migraine

Subacute

• Alcohol related cerebellar degeneration
• Paraneoplastic cerebellar degeneration (anti-Yo, anti-Hu, anti-Ri), anti-GAD ataxia
• Gluten ataxia (coeliac disease)
• Vitamin B12, vitamin E, thiamine and copper deficiency
• Hypothyroidism
• Creutzfeldt Jakob disease
• Neurosyphilis (tabes dorsalis), HIV, progressive multifocal leukoencephalopathy
• Chronic drug toxicity
• Normal pressure hydrocephalus (gait predominant)

Chronic progressive

• Autosomal dominant spinocerebellar ataxias
• Friedreich ataxia and other recessive ataxias, ataxia telangiectasia
• Wilson disease
• Fragile X associated tremor ataxia syndrome
• Mitochondrial disease
• Multiple system atrophy, cerebellar type
• Late onset idiopathic cerebellar ataxia
• Sensory neuronopathy and neuropathy (diabetic, paraproteinaemic, chronic inflammatory demyelinating polyneuropathy, Sjogren syndrome)
• Cervical myelopathy
• Cerebellar structural lesions: Chiari malformation, haemangioblastoma, vascular malformation

Episodic

• Episodic ataxia types 1 and 2
• Vestibular migraine, transient ischaemic attack

Reasoning. Establish tempo, localise to cerebellar, sensory, vestibular or frontal, and then match to cause. Treat acute ataxia as a stroke or posterior fossa emergency until imaging shows otherwise.

First line. Capillary glucose, ECG, vital signs, and bloods: full blood count, urea, electrolytes, liver function, calcium, magnesium, glucose, thyroid function, vitamin B12, folate, ESR and CRP. Urine toxicology and drug levels (phenytoin, carbamazepine, lithium) as relevant.

Imaging. MRI brain with diffusion weighted imaging and MR or CT angiography of the head and neck for acute ataxia. CT head is quick and identifies haemorrhage and hydrocephalus, but its sensitivity for early posterior fossa infarction is low, so a normal CT does not exclude stroke. MRI brain with contrast for subacute and chronic ataxia (atrophy pattern, tumour, demyelination). MRI spine for sensory level, bladder involvement or myelopathy.

Targeted tests

• Thiamine status is a clinical diagnosis in the presence of risk factors; do not wait for levels.
• Vitamin E, copper and caeruloplasmin (with slit lamp examination and 24 hour urinary copper if Wilson disease is suspected under age 50).
• Coeliac serology (tissue transglutaminase IgA with total IgA), HIV, syphilis serology, antinuclear and anti-Ro and anti-La antibodies, anti-GAD, and a paraneoplastic antibody panel.
• Cerebrospinal fluid (after imaging): cells, protein, oligoclonal bands, infection and autoimmune studies.
• CT chest, abdomen and pelvis, and FDG PET if paraneoplastic disease is suspected.
• Nerve conduction studies for sensory neuropathy.
• Genetic testing for hereditary ataxia, after family history and counselling.

Limitations. Paraneoplastic antibodies can be absent despite paraneoplastic disease. Genetic panels leave a large share of hereditary ataxias unexplained. MRI may be normal in early disease.

Acute stroke (including cerebellar infarction)

• Alteplase 0.9 mg/kg IV (maximum 90 mg), 10 percent as a bolus over 1 minute and the remainder over 60 minutes, within 4.5 hours of onset after haemorrhage is excluded and exclusion criteria are checked. Alternatively tenecteplase 0.25 mg/kg IV as a single bolus (maximum 25 mg). Blood pressure under 185/110 mmHg before and under 180/105 mmHg for 24 hours after thrombolysis.
• Aspirin 300 mg orally daily, started 24 hours after thrombolysis, or immediately if thrombolysis is not given and haemorrhage is excluded.
• Cerebellar infarct or haemorrhage with brainstem compression or hydrocephalus: immediate neurosurgical referral for decompression or external ventricular drainage.

Wernicke encephalopathy (give before glucose or carbohydrate)

• Thiamine 500 mg IV infused over 30 minutes every 8 hours for 2 to 3 days, then 250 mg IV daily for 5 days (evidence on optimal dosing is limited), then 100 mg orally three times daily. Correct magnesium (hypomagnesaemia impairs thiamine action). Monitor for anaphylaxis (rare).

Vitamin B12 deficiency with neurological signs. Hydroxocobalamin 1 mg IM on alternate days until no further improvement (up to 3 weeks), then 1 mg IM every 2 months. Never give folic acid alone first.

Guillain Barré and Miller Fisher syndromes. Intravenous immunoglobulin 0.4 g/kg daily for 5 days. Monitor vital capacity and bulbar function; renal function and thrombosis risk with immunoglobulin.

Multiple sclerosis relapse. Methylprednisolone 1 g IV daily for 3 to 5 days, with gastric protection and glucose monitoring.

Other causes. Stop or reduce toxic drugs, with serum level monitoring. Gluten free diet for coeliac disease. Levothyroxine for hypothyroidism. Copper replacement for copper deficiency. Cancer directed treatment for paraneoplastic syndromes. Genetic counselling and symptomatic physiotherapy for hereditary ataxias.

Supportive care. Physiotherapy for gait and balance, occupational therapy, walking aids, falls prevention, speech and swallowing assessment, and alcohol cessation.

Monitoring. Neurological observations in acute cases; repeat scoring of ataxia severity at follow up; vitamin and electrolyte levels after replacement.

Referral and escalation. Immediate stroke or neurosurgical referral for acute onset. Neurology for subacute and chronic progressive ataxia. Oncology and specialist neurology for paraneoplastic disease. Urgent specialist referral when Wernicke encephalopathy is suspected.

Admission criteria. All acute or rapidly progressive ataxia, suspected Wernicke encephalopathy, hydrocephalus, inability to walk safely, or need for urgent investigation. Chronic stable ataxia can be managed as an outpatient.

Discharge and safety netting. Return urgently for headache, vomiting, drowsiness, new weakness or sensory loss, double vision, swallowing difficulty or falls. Advise on driving restrictions and home safety.