Ataxia & Cerebellar Disorders

Localizing Ataxia

Ataxia is poorly coordinated movement without weakness. It arises from the cerebellum, from lost proprioceptive input (sensory ataxia) or from vestibular dysfunction, and the bedside exam separates them.

Vermis (midline) lesions. The vermis governs axial muscles and posture, so midline damage causes truncal ataxia: a wide-based, staggering gait, inability to stand with feet together or walk heel-to-toe, and truncal titubation, while finger-nose testing may be nearly normal. Chronic alcohol use degenerates the anterior superior vermis, affecting gait and legs but sparing the arms. In a child, progressive truncal ataxia with morning headache and vomiting suggests a midline posterior fossa tumor such as medulloblastoma.

Hemispheric lesions. The lateral hemispheres coordinate the limbs on the same side, producing dysmetria on finger-nose and heel-shin testing, an intention tremor that worsens near the target, dysdiadochokinesia, impaired check with rebound, hypotonia, and veering toward the lesion. The ipsilateral pattern reflects a double crossing: dentate output crosses in the superior cerebellar peduncle to the contralateral thalamus and motor cortex, and the corticospinal tract crosses back in the medulla. Either site may add gaze-evoked nystagmus and scanning dysarthria.

Sensory ataxia. Proprioceptive loss from dorsal column disease (B12 or copper deficiency, tabes dorsalis) or large-fiber neuropathy and ganglionopathy is compensated by vision: the patient is steadier with eyes open and falls when they close (positive Romberg sign), with impaired vibration and position sense, a stomping gait, pseudoathetosis of outstretched fingers and often reduced reflexes.

Acute Ataxia

Cerebellar hemorrhage and infarction. Hypertensive hemorrhage or vertebral/PICA infarction presents with sudden vertigo, vomiting, occipital headache, inability to stand or walk, ipsilateral limb ataxia, nystagmus and dysarthria. Inability to walk unaided is a central red flag in the dizzy patient; people with peripheral vestibular disease can usually walk, if unsteadily. Noncontrast CT shows hemorrhage and hydrocephalus; infarcts need diffusion-weighted MRI because early CT often misses them in the posterior fossa.

The posterior fossa has little room. Hematoma or infarct edema (peaking around days 2–4) compresses the fourth ventricle and brainstem, causing obstructive hydrocephalus, drowsiness, gaze palsy, herniation and death within hours. Hemorrhage larger than 3 cm (about 15 mL), neurologic decline, brainstem compression or hydrocephalus demands emergency suboccipital decompression with evacuation; a ventricular drain alone is not adequate.

Drugs and toxins. Alcohol, benzodiazepines, barbiturates, phenytoin, carbamazepine, lithium, metronidazole and high-dose cytarabine all cause cerebellar dysfunction. Phenytoin toxicity tracks with level — nystagmus above 20 μg/mL, ataxia above 30, lethargy and confusion above 40 — and long-term use causes cerebellar atrophy. Lithium levels climb with dehydration, thiazides, NSAIDs and ACE inhibitors. Metronidazole causes reversible, symmetric dentate nucleus lesions. Check a level, hold the drug and support the patient.

Miller Fisher syndrome. A Guillain-Barré variant following an infection (often Campylobacter jejuni) by days to weeks, with external ophthalmoplegia, ataxia and areflexia, sometimes ptosis or facial weakness. Most patients have anti-GQ1b antibodies, which target gangliosides concentrated in the oculomotor nerves, and CSF shows albuminocytologic dissociation. Recovery over weeks to months is the rule; IVIG or plasma exchange is used when limb or respiratory weakness overlaps with GBS.

Children. Acute post-infectious cerebellar ataxia is the commonest cause of acute ataxia at ages 2–5: abrupt truncal and gait ataxia (the child refuses to walk), nystagmus and dysarthria 1–3 weeks after varicella or another viral illness, in an alert, afebrile child without meningismus. It resolves over weeks, but it is a diagnosis of exclusion.

Hereditary Ataxias

Friedreich ataxia. The most common inherited ataxia is autosomal recessive, usually from homozygous GAA expansions in intron 1 of FXN on chromosome 9 that silence frataxin, a mitochondrial protein needed for iron-sulfur cluster assembly. Mitochondrial iron overload and oxidative stress injure the dorsal root ganglia, dorsal columns, spinocerebellar and corticospinal tracts, myocardium and pancreatic β-cells. Onset is usually at 10–15 years with progressive gait and limb ataxia, dysarthria, loss of vibration and position sense, and areflexia with extensor plantar responses. Pes cavus and kyphoscoliosis are common, and diabetes and hearing and visual loss follow. Hypertrophic cardiomyopathy is the leading cause of death through heart failure and arrhythmia, so patients need ECG, echocardiography and glucose screening. Omaveloxolone, an Nrf2 activator, is the first approved disease-specific drug (age 16 and older).

Absent ankle reflexes with upgoing toes narrow the differential to Friedreich ataxia and B12 deficiency (subacute combined degeneration).

Spinocerebellar ataxias (SCAs). Autosomal dominant disorders, most from CAG (polyglutamine) expansions — SCA1, 2, 3 (Machado-Joseph disease, most common worldwide), 6 and 7 — causing adult-onset progressive ataxia, dysarthria and nystagmus with type-specific extras such as slow saccades (SCA2) and retinal degeneration (SCA7). Repeats lengthen across generations, producing anticipation. Diagnosis is genetic and care is supportive.

Ataxia-telangiectasia (A-T). Autosomal recessive loss of ATM, a kinase that signals DNA double-strand breaks. Truncal ataxia starts as the toddler learns to walk, followed by oculomotor apraxia and, by early school age, conjunctival telangiectasias. IgA, IgG-subclass and T-cell deficiency cause sinopulmonary infections, lymphoma and leukemia are common, and extreme radiosensitivity means avoiding unnecessary X-ray imaging. Serum AFP is elevated in nearly all patients and is the best screening test.

Acquired Chronic Ataxia

Treatable causes first. Chronic ataxia warrants MRI and a search for reversible causes: hypothyroidism (TSH), vitamin E deficiency, B12 and copper deficiency (sensory ataxia), celiac disease, and a careful alcohol and medication history.

Vitamin E deficiency. Fat malabsorption — cystic fibrosis, chronic cholestasis, abetalipoproteinemia — depletes vitamin E and produces a spinocerebellar syndrome of ataxia, areflexia, proprioceptive loss, ophthalmoplegia and retinopathy that mimics Friedreich ataxia. Ataxia with isolated vitamin E deficiency (TTPA gene) looks identical but responds to high-dose supplementation.

Paraneoplastic and degenerative causes. Subacute, severe pancerebellar ataxia in an adult raises concern for a paraneoplastic syndrome — anti-Yo with ovarian or breast cancer, anti-Hu with small cell lung cancer — and prompts antibody testing and a cancer search. The cerebellar form of multiple system atrophy pairs progressive ataxia with early autonomic failure. Whatever the cause, balance and gait therapy and fall prevention help every patient.