Cerebellar Dysfunction

Etiology

Cerebellar dysfunction results from a heterogeneous group of disorders and can occur in isolation or as part of a range of neurological or systemic features. These defects can develop secondary to vascular (eg, stroke and hemorrhage), idiopathic, iatrogenic (eg, drug), traumatic, autoimmune, metabolic, infective, inflammatory, neoplastic, toxic, and rare genetic disorders. 

Many etiologies are associated with dysfunction of specific cerebellum regions. Etiologies that tend to cause bilateral cerebellar dysfunctions include:

• Multiple sclerosis (demyelination) 
• Posterior circulation stroke
• Bilateral cerebellar pontine angle lesions or space-occupying lesions, eg, neurofibromatosis and schwannoma
• Paraneoplastic syndromes
• Multiple system atrophy
• Toxins and drugs (eg, alcohol, phenytoin, lithium, and carbamazepine)
• Metabolic conditions (eg, thyroid disorders, B12 deficiency, Wilson disease, and celiac disease)
• Infectious etiologies including enteroviruses, HIV, neurosyphilis, toxoplasmosis, borreliosis, and Creutzfeldt–Jakob disease
• Inflammatory conditions (eg, Guillain-Barré syndrome)
• Hereditary conditions including ataxia telangiectasia, Friedreich ataxia, Von Hippel-Lindau syndrome, spinocerebellar ataxias

Unilateral cerebellar dysfunction is associated with the following etiologies:

• Unilateral posterior circulation ischemic or hemorrhagic stroke
  • Part of lateral medullary syndrome 
  • Hemiparesis with ataxia following a lacunar stroke
• Multiple sclerosis (demyelination) 
• Space-occupying lesions in the posterior cranial fossa, including abscesses (eg, tuberculosis and staphylococcal infection) and tumor
• Unilateral cerebellar pontine angle lesions or space-occupying lesions (eg, neurofibromatosis and schwannoma)
• Multiple system atrophy

Etiologies that tend to cause spastic paraparesis with cerebellar signs include:

• Multiple sclerosis (demyelination) 
• Friedreich ataxia
• Spinocerebellar ataxia
• Arnold-Chiari malformation [3]
• Syringomyelia, syringobulbia [4]

Epidemiology

The prevalence of cerebellar dysfunction varies according to the underlying etiology. For instance, stroke is more common in patients older than 45, and genetic causes are typically diagnosed during childhood. Studies have not revealed differences in incidence or prevalence between males and females in primary diseases, but in secondary etiologies, the incidence can vary depending on gender. However, men have demonstrated more neurological gait problems compared to women.[5]

History and Physical

Clinical Neurological Evaluation

In addition to a thorough clinical history, a neurological examination is the primary clinical assessment performed to diagnose cerebellar dysfunction. Neurologic clinical testing is utilized to determine if an impairment is present and to indicate which cranial nerve or brain region is affected. The following findings on neurological testing are suggestive of cerebellar impairment:

• Gaze test: Patients are asked to maintain a gaze at a fixed point from various angles. A patient with impairment has gaze-evoked nystagmus and hypometric or hypermetric saccadic eye movements when looking to either side; the fast phase of nystagmus will be in the direction of gaze, and on the generation of saccadic eye movements, the patient may undershoot or overshoot, with resultant small corrective saccades. The inability to maintain a steady gaze indicates a central or peripheral vestibular system lesion.
• Scanning speech: Patients may have a cerebellar staccato speech pattern, which refers to unconnected or detached notes in music.
• Upper limb movement tests: Patients with cerebellar dysfunction may have findings of impaired movement when asked to perform specific actions (eg, finger–nose test), including an intention tremor, a tremor that increases in amplitude as a finger approaches the target, past-pointing, dysmetria, and dysdiadochokinesis in which patients have difficulties with making rapid alternating movements, such as pronation-supination. An early sign of dysdiadochokinesis may be that the patient moves their hand as if turning the pages of a book when asked to flip their hands back and forth quickly. The finger–nose test should be undertaken slowly and carefully, as rapidly carrying out the test tends to miss early cerebellar signs.
• Rebound phenomenon: During this test, the patient is asked to maintain his arms outstretched with closed eyes. Downward pressure is applied to the arms and suddenly released. Patients with cerebellar dysfunction will shoot their arms upward when pressure is released and oscillate before returning to the original position. The cerebellum functions as a calibrator of forces, and dysfunction generates inappropriate muscle forces to fix the limb in a particular position.
• Patellar reflex test: Due to a failure to calibrate muscle forces, patients with cerebellar impairment have an abnormal "dampening" of the elicited movement and will keep swinging their leg >4 times following the patellar tendon percussion; hypotonia of arms and legs may also be noted.
• Gait testing: Patients with cerebellar dysfunction may be noted to have an ataxic gait. However, sensory ataxias should be excluded. A positive Romberg test or pseudoathetosis, an apparent writhing of fingers of outstretched hands when eyes are closed due to proprioceptive impairment, impaired joint position sense, and distal weakness associated with a peripheral sensory or sensorimotor neuropathy are consistent with an impaired sensory pathway rather than cerebellar dysfunction. Truncal ataxia associated with cerebellar impairment is often demonstrable in sitting or standing. A gait examination is also needed to exclude other gait disorders.
• Heel–shin test:  Patients are asked to make a circular movement, running the heel down the contralateral shin and raising it off the shin once it reaches the ankle. Then, the heel is placed on the knee again. Simply gliding one heel up and down the opposite shin will miss early ataxia. The inability to keep their foot on the shin is noted in patients with cerebellar dysfunction.[6][7][2][8]

A simple mnemonic to remember some of the cerebellar signs is DANISH:

• Dysdiadochokinesia or dysmetria
• Ataxia
• Nystagmus
• Intention tremor
• Speech (slurred or scanning)
• Hypotonia

Additional Clinical Assessments

In addition to the neurological examination, clinical history and physical examinations to help determine the underlying etiology should be performed, including: 

• Demyelination: Clinicians should look for evidence of a relative afferent pupillary defect, internuclear ophthalmoplegia, or upper motor neuron signs, especially in a young woman.

• Vascular: Signs and symptoms of infarction or hemorrhage may be observed. 

• Space-occupying lesion: If unilateral or markedly asymmetrical signs are present, clinicians should conduct a cranial nerve examination to exclude cerebral pontine angle tumor. 

• Alcoholic degeneration: A history of alcohol abuse is suggestive of this etiology. Therefore, clinicians should perform an alcohol intake history (eg, CAGE questionnaire) as clinically indicated.

• Drugs: Pharmacologic etiologies (eg, carbamazepine, phenytoin, and barbiturates) may be indicated by medication history or clinical signs, eg, gingival hyperplasia due to phenytoin.

• Metabolic: Cerebellar and sensory ataxias may be secondary to metabolic disorders (eg, B12, copper, or a vitamin E deficiency).[9] 

• Hypothyroidism: Clinical features including weight gain, mood disorder, sleep and bowel habit dysfunction, or an association with other autoimmune diseases may be noted. 

• Nutritional: Celiac disease may be suggested by bowel history.

• Paraneoplastic: Clinical features associated with small cell lung cancer, hepatocellular carcinoma or chronic liver diseases, breast, gynecological, and testicular tumors, and Hodgkin lymphoma may be observed, including clubbing, enlarged lymph nodes, tar staining, liver enlargement, and palpated masses.

• Genetic: Various inherited conditions may be suggested by clinical examination. Spinocerebellar ataxias may have various additional signs, including upper motor neuron and extrapyramidal signs, peripheral neuropathy, and ophthalmoplegia of autosomal dominant inheritance. Friedreich ataxia, which has autosomal recessive inheritance, is associated with peripheral neuropathy, spasticity, optic atrophy (fundoscopy), diabetes mellitus, hypertrophic cardiomyopathy, and deafness. Friedreich ataxia has a typical onset between 8 and 15 years of age, and patients frequently use wheelchairs. Ataxia-telangiectasia is also an autosomal recessive condition; however, clinical signs include skin and eye telangiectasia, dystonia, and chorea. Von Hippel–Lindau syndrome with cerebellar haemangioblastomas associated with renal cell carcinoma, unilateral or bilateral pontocerebellar atrophy and hypoplasia, and multiple system atrophy may also present with predominant cerebellar features.[10]

Evaluation

Additional diagnostic testing is primarily conducted to identify the underlying etiology of cerebellar symptoms.[11][12] Diagnostic studies that may be considered based on clinical indications include:

• Brain and spinal cord magnetic resonance imaging
• Laboratory studies, including complete blood count with erythrocyte sedimentation rate, liver function tests, vitamin B12 level, thyroid stimulating hormone, free T3 and T4, copper level studies, paraneoplastic screen, antitissue transglutaminase antibody, infection and inflammation screening tests, drug levels (eg, carbamazepine, phenytoin, and lithium)
• Lumbar puncture to examine cerebral spinal fluid for oligoclonal bands
• Electromyography and nerve conduction studies 
• Visual evoked potentials
• Genetic testing [13]

Treatment / Management

Treatment of cerebellar dysfunction initially involves diagnosing the underlying causes. A proper diagnosis leads to more accurate treatment plans. Management also includes supportive therapies, which can require an interdisciplinary approach that incorporates physiotherapy, occupational therapy, and medications. Therefore, supportive therapy plans range in complexity based on the severity of symptoms and etiology. For instance, patients with vitamin deficiency can be educated and prescribed proper supplementation to increase their levels with laboratory studies to ensure the achievement of therapeutic levels of vitamins.[9] Furthermore, patients can benefit from rehabilitation, gait training, gait assistive devices, and fall preventive measures. Commonly used exercise interventions, including coordination training, muscle strength, power, and resistance training, can improve gait and balance impairment in older people.

Differential Diagnosis

The suspicion of gait disturbances demands a broad differential encompassing numerous etiologies. When evaluating patients with cerebellar dysfunction, the following differential diagnoses should excluded:

• Ataxias: Vestibular and sensory ataxia [14]
• Neurologic conditions: Parkinson disease, dementia, stroke, subacute combined degeneration, amyotrophic lateral sclerosis
• Metabolic conditions: Diabetes mellitus, encephalopathy, obesity, vitamin B12 deficiency, uremia

Prognosis

The prognosis of cerebellar disturbances depends on the underlying etiology. Metabolic and nutritional etiologies of cerebellar dysfunction have a relatively good prognosis. Some neurologic diseases must be treated symptomatically only and often worsen over time.

Complications

Complications and adverse events associated with cerebellar dysfunction include:

• Falls
• Paralysis
• Dizziness
• Gait disorders and bed-bound state
• Worsening tremor
• Psychosocial stigma
• Raised intracranial pressure
• Developmental milestone delay in children