Continuing Education Activity

The cerebellum maintains our coordination and balance. Cerebellar dysfunction causes difficulty with coordination, imbalance, and gait disorders. Possible etiologies are vascular, idiopathic, traumatic, autoimmune, metabolic, infectious, inflammatory, and neoplastic. Neurological evaluation is necessary for diagnosis and treatment. Cerebellar dysfunction can have a tremendous impact on patients, especially on the quality of life, balance, gait, morbidity, and mortality. This activity reviews the role of the interprofessional team in the evaluation and management of cerebellar dysfunction.

Objectives:

• Describe the pathophysiology of cerebellar dysfunction.
• Review the evaluation of cerebellar dysfunction.
• Outline the management of cerebellar dysfunction.
• Explain to enhance a health professional's understanding of cerebellar dysfunction.

Introduction

The cerebellum, located under the posterior cerebral cortex in the posterior cranial fossa, just posterior to the brainstem, has diverse connections to the brain stem, cerebrum, and spinal cord.[1]

Embryologically it develops from hindbrain or rhombencephalon. The cerebellum subdivides into two hemispheres connected by the vermis, a central midline part.Any midline cerebellar lesions manifest as imbalance, while hemispheric cerebellar lesions result mainly in incoordination.[2]

The cerebellum maintains our motor equilibrium and calibration of movements. It is an essential region of the brain playing a central role in maintaining our gait, stance, and balance, as well as the coordination of goal-directed movements and complex movements. Dysfunction manifests as clumsiness and "drunken" gait. 

The cerebellum contains a considerable number of neurons in a limited volume, possibly due to the folding of the cortex of the cerebellum, and the neurons are mainly present close to periphery.

Cerebellar dysfunction causes balance problems and gait disorders along with difficulties in coordination resulting in ataxia, uncoordinated movements, imbalance, speech problems(dysarthria), visual problems (nystagmus) and vertigo as a part of the vestibulocerebellar system. There are several reasons for these defects. Some are vascular (due to stroke, hemorrhage), idiopathic, iatrogenic, traumatic, autoimmune, metabolic, infectious, inflammatory, neoplastic, and some rare genetic disorders. An etiological evaluation is necessary for the diagnosis of cerebellar dysfunction and the treatment of cerebellar disorders.

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. There are several reasons for these defects. These can be vascular (due to stroke, hemorrhage), idiopathic, iatrogenic (drug), traumatic, autoimmune, metabolic, infective, inflammatory, neoplastic, toxic, and rare genetic disorders. We can divide this according to the involvement of one or both sides.

A. Bilateral cerebellar dysfunctions (most important causes are):

• Multiple sclerosis (demyelination) 
• Posterior circulation stroke
• Bilateral cerebellar pontine (CP) angle lesions or space-occupying lesions, e.g., neurofibromatosis, schwannoma
• Paraneoplastic syndromes
• MSA (multiple system atrophy)
• Toxin & Drugs: alcohol, phenytoin, lithium, carbamazepine.
• Metabolic: thyroid abnormality (hypothyroid), B12 deficiency, Wilson disease, celiac disease 
• Infectious: enteroviruses, HIV, neurosyphilis, toxoplasmosis, borreliosis, Creutzfeldt–Jakob disease
• Inflammatory: GBS (Miller Fischer variant)
• Hereditary: ataxia telangiectasia), Friedreich ataxia, Von Hippel-Lindau syndrome), spinocerebellar ataxias)

B. Unilateral cerebellar dysfunctions (most important causes are):

• Unilateral posterior circulation ischemic/hemorrhagic stroke
  • Part of lateral medullary syndrome (LMS)
  • Hemiparesis with ataxia (following lacunar stroke)
• Multiple sclerosis (demyelination) 
• Space occupying lesions (SOL) in the posterior cranial fossa, e.g., abscess (tuberculosis, staphylococcal infection), tumor
• Unilateral cerebellar pontine (CP) angle lesions or space-occupying lesions, e.g., neurofibromatosis, schwannoma
• Multiple system atrophy

C. Spastic paraparesis with cerebellar signs (the most important causes are):

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

Epidemiology

This factor strongly varies according to etiologies. Stroke is more common after 45 years, and genetic causes are typically diagnosed during childhood. Research has not revealed any differences in incidence or prevalence between males and females in primary diseases, but according to etiology, it can vary. Men have demonstrated more neurological gait problems compared to women.[5]

Pathophysiology

Cerebellar syndrome results from a heterogeneous group of disorders and can occur in systemic features or isolation or as part of a range of neurological presentations. The patient will often undergo a cerebellar examination by instructions referring to coordination, imbalance, or difficulty performing smooth movements and goal-directed tasks. There are several reasons for these defects, as discussed here.[6]

History and Physical

Cerebellar examinations are mandatory to diagnose exact etiologies.An important part of cerebellar examinations:[7][8][2][9]

• Gaze-evoked nystagmus and hypo- or hypermetric saccadic eye movements: on 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 under- or overshoot, with resultant small corrective saccades.
• Cerebellar ‘staccato’ speech (in music, staccato refers to unconnected or detached notes)
• Upper limb signs of
  • intention tremor (tremor that increases in amplitude as a finger approaches the target)
  • past-pointing,
  • dysmetria and
  • dysdiadochokinesis (difficulties with making rapid alternating movements, such as pronation-supination (an early sign may be that the patient moves their hand as if they are turning the pages of a book).
• The finger–nose test should be undertaken slowly and carefully as carrying out the test in a rapid fashion tends to miss early cerebellar signs.
• Rebound phenomenon: the patient is asked to maintain his arms in the outstretched position with eyes closed. Downward pressure is applied to the arms and is released suddenly. In a cerebellar syndrome, the arms will shoot upward when pressure is released and will oscillate before returning to the original position. The cerebellum functions as a calibrator of forces, and dysfunction results in the generation of inappropriate muscle forces to fix the limb in a particular position
• Hypotonia of arms and legs (reduced tone of limbs) 
• Look for evidence of a sensory rather than cerebellar ataxia: positive Romberg’s test or pseudoathetosis (apparent writhing of fingers of outstretched hands when eyes are closed, due to proprioceptive impairment). If sensory ataxia is suspected, look for sensory impairment (especially joint position sense) and distal weakness associated with a peripheral sensory or sensorimotor neuropathy. 
• Ataxic gait (examination of gait is needed to exclude other gait disorders too )
• Heel–shin ataxia (ask the patient to make a circular movement, with the heel raised off the shin once it has reached the ankle, before placing it on the knee again. Simply gliding one heel up and down the opposite shin will miss early ataxia)
• Truncal ataxia (demonstrable in sitting position or while standing)
• Pendular reflexes: the movement elicited by percussion is not dampened, resulting in swinging back and forth of the limb. Once again, this is due to a failure of calibration of muscle forces, resulting in abnormal ‘dampening.’ 

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

• Dysdiadochokinesia/ dysmetria
• Ataxia
• Nystagmus
• Intention tremor
• Speech - slurred or scanning
• Hypotonia

Following Examinations are required to find out and correlate the etiology: 

• Demyelination: look for evidence of an RAPD (relative afferent pupillary defect), internuclear ophthalmoplegia, or upper motor neuron signs, especially in a young woman.
• Vascular: infarction or hemorrhage. 
• Space-occupying lesion (especially if unilateral or markedly asymmetrical signs, do cranial nerve examination to exclude CP angle tumor). 
• Alcoholic degeneration (History of alcohol intake with CAGE questionnaire)
• Drugs: e.g., carbamazepine, phenytoin (gum examination), and barbiturates. 
• Metabolic: B12, copper, or vitamin E deficiency (may also cause sensory ataxia)[10] 
• Hypothyroidism (Weight gain, mood, sleep, bowel habit, an association of other autoimmune diseases) 
• Nutritional: Celiac disease (bowel history and association of other autoimmune diseases) 
• Paraneoplastic: associated with small cell lung, breast, gynecological and testicular tumors, and Hodgkin lymphoma. Following examinations are relevant: clubbing, lymph nodes on palpation, tar staining, Features of HCC (hepatocellular carcinoma) and CLD (chronic liver diseases) 
• Genetic:
  • Spinocerebellar ataxias: may have a variety of additional signs, including UMN and extrapyramidal signs, peripheral neuropathy, and ophthalmoplegia of autosomal dominant inheritance.
  • Friedreich ataxia: ataxia with peripheral neuropathy, spasticity, optic atrophy (fundoscopy), diabetes mellitus, hypertrophic cardiomyopathy, and deafness. Typical onset is between 8 to 15 years of age; autosomal recessive inheritance. Patients are frequently wheelchair-bound.
  • Ataxia-telangiectasia: skin and eye telangiectasia, dystonia and chorea; autosomal recessive inheritance.
  • Von Hippel–Lindau syndrome with cerebellar haemangioblastomas (associated with renal cell carcinoma)
  • Multiple system atrophy with predominant cerebellar features (often referred to as MSA-C)
  • Unilateral or bilateral pontocerebellar atrophy and hypoplasia[11]

Evaluation

Investigations to find out most likely cause:[12][13]

• Imaging: Brain and spinal cord MRI
• Some blood tests:
  • CBC with ESR
  • Liver function tests
  • Vitamin B12 level
  • TSH, fT3, fT4
  • Copper level studies
  • Paraneoplastic screen
  • Anti-tissue transglutaminase antibody,
  • Screen for infection and inflammation,
  • Some drug levels (carbamazepine, phenytoin, lithium)
• Lumbar puncture (to examine CSF for oligoclonal bands)
• Electromyography (EMG) and nerve conduction studies (NCS)
• Visual evoked potentials
• Genetic testing[14]

Treatment / Management

Treatment of cerebellar dysfunction initially involves diagnosing the underlying causes. A proper diagnosis leads to more accurate treatment plans.

These plans can require a multidisciplinary approach incorporating, physiotherapy, occupational therapy, and medications. The treatment plans range in complexity based on the severity of symptoms and etiology.Patients with vitamin deficiency can be educated and prescribed proper supplementation to increase their body’s levels. Following up with routine laboratory work is essential in these patients to ensure the achievement of therapeutic levels of vitamins.[10]Patients can benefit from rehabilitation, gait training, use of gait assistive devices, and fall preventive measures. Commonly used exercise interventions such as coordination training, muscle strength, power, as well as resistance training, can improve routine and maximum gait and balance problems in the elderly.

Differential Diagnosis

The suspicion of gait disturbances demands a broad differential encompassing numerous etiologies. The following potential causes should be ruled out to come up with a final diagnosis.Other form of Ataxias: Vestibular and sensory ataxia[15]

Neurologic: Parkinson, dementia, stroke, subacute combined degeneration, amyotrophic lateral sclerosis

Metabolic: Diabetes mellitus, encephalopathy, obesity, vitamin B12 deficiency, uremia

Prognosis

The prognosis of cerebellar disturbances depends on the 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

The risks of having cerebellar dysfunction should be explained to the patient, so they become aware. These risks include:

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

Consultations

Patient education and counseling, according to the patient's need, and formation of a multidisciplinary team for better management and patient outcomes.

• Neurologist
• Neurosurgeon
• Dietician
• Endocrinologist
• Geneticist
• Psychiatrist
• Physical therapist
• Occupational therapist
• Social worker

Deterrence and Patient Education

Patient education is a vital part of identifying cerebellar dysfunctions; early detection can lead to better outcomes and prevent complications. Corrective surgery, genetic counseling, rehabilitation, gait training, use of supportive devices, and fall prevention measures require implementation.

Enhancing Healthcare Team Outcomes

There are several reasons behind cerebellar dysfunction. An etiological evaluation is necessary for the diagnosis of cerebellar dysfunction and treatment. Cerebellar dysfunction has a tremendous impact on patients, especially on the quality of life, gait and balance problems, morbidity, and mortality. The role of rehabilitative strategies is critical for most underlying etiologies. A collaborative multidisciplinary approach can provide comprehensive patient care, enhance team performance, and ultimately improve patient outcomes.