Cerebellar Dysfunction – Causes, Symptoms, Treatment

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.

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.

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.

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.

Embryologically it develops from the 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.

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 a “drunken” gait.

Associated diseases

Diseases that are specific to the brain, as well as diseases that occur in other parts of the body, can cause neurons to die in the cerebellum. Neurological diseases that feature cerebellar degeneration include:

  • ischemic or hemorrhagic stroke, when there is lack of blood flow or oxygen to the cerebellum
  • cerebellar cortical atrophy, multisystem atrophy, and olivopontocerebellar degeneration, progressive degenerative disorders in which cerebellar degeneration is a key feature
  • Friedreich’s ataxia, and other spinocerebellar ataxias, which are caused by inherited genetic mutations that result in ongoing loss of neurons in the cerebellum, brain stem, and spinal cord
  • transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease) in which abnormal proteins cause inflammation in the brain, including the cerebellum
  • multiple sclerosis, in which damage to the insulating membrane (myelin) that wraps around and protects nerve cells can involve the cerebellum
  • chronic alcohol abuse that leads to temporary or permanent cerebellar damage
  • paraneoplastic disorders, in which a malignancy (cancer) in other parts of the body produces substances that cause immune system cells to attack neurons in the cerebellum

Causes of Cerebellar Dysfunction

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)
  • Syringomyelia, syringobulbia

Ataxia may occur due to abnormalities in the nervous system’s different areas, including the brain, spinal cord, nerves, and nerve roots. The different types of ataxia often have similar or overlapping causes in the same patient.

  • Focal lesions – due to tumors, stroke, multiple sclerosis, or inflammation
  • Metabolic – due to substances such as alcohol, antidepressant drugs, and antiepileptic drugs
  • Poisoning – due to radiation
  • Vitamin B12 deficiency
  • Thyroid disease – hypothyroidism
  • Head injury
  • Coeliac disease (gluten ataxia)
  • Hereditary – Friedreich ataxia, ataxia-telangiectasia, Nieman-Pick disease, fragile X associated ataxia/tremor syndrome
  • Arnold-Chiari malformation
  • Wilson disease
  • Succinic semialdehyde dehydrogenase deficiency

Symptoms of Cerebellar Dysfunction

Clinical Presentations associated with cerebellar dysfunction:

  • Ataxia: Lack of normal coordination of movements.
  • Gait problems: Lesions of the cerebellum typically affect the same side of the body, and patients fall towards the side of the lesion.
  • Intention Tremor: Low-frequency tremor (below 5Hz) with the voluntary movement of the limb. The tremor is exaggerated when the limb approaches the endpoint of its deliberate movement (cerebellar tremor). The tremor is not present at rest (a feature of parkinsonian tremor).
  • Dysdiadochokinesia: The inability to perform fast, alternating movements.
  • Decomposition of Movement (abnormal coordination): Movement cannot occur smoothly and gets divided into its components.
  • Dysmetria: Overshooting or undershooting the target. Patients are unable to reach the target at the first attempt and make corrections.
  • Dysarthria: This is the inability to articulate words properly.

Signs of Cerebellar Vermis and Flocculonodular Lobe Lesions

  • Gait Ataxia: Abnormal coordination of movements while walking. Patients have a wide-based, drunk-like unsteady, stumbling gait, which is also called “staggering gait.” The patient will be unable to walk on toes or heels and in tandem; also known as truncal ataxia.
  • Titubation: Tremor (noodling) of the head or axial body. If severe, the patient can’t sit or stand without help.
  • Nystagmus: Commonly bilateral, these are involuntary, rapid, repetitive eye movements, which can be horizontal or vertical.

Signs of Cerebellar Hemisphere (Cerebrocerebellum) Lesions

  • Limb ataxia: Also referred to as appendicular ataxia. This condition presents with lesions of the intermediate and lateral portions of the cerebellar hemisphere. The degree and locations of ataxia depend on the somatotopic projection of the body parts of the involved cerebellar hemisphere. It can present as dysmetria, dysdiadochokinesis, hypotonia or intention tremor in one or both extremities. Patients can also present with dysarthria.

Diagnosis of Cerebellar Dysfunction

Common cerebellar neurological signs are as follows:

Extraocular movements

  • Nystagmus: The pattern of nystagmus is different in etiologies of central origin, such as a cerebellar lesion, as compared to etiologies of peripheral origin such as vestibulopathy. In etiologies of peripheral origin, the nystagmus is unidirectional irrespective of the direction of gaze and worsens when the patient directs their gaze towards the healthy ear (Alexander’s law).
  • Impaired smooth pursuits: In cerebellar lesions, patients are unable to track objects with smooth eye movements. Instead, catch-up saccades are the presentation.
  • HINTS exam: HINTS exam is a combination of three maneuvers (Head Impulse test, Nystagmus, test of Skew) to help differentiate vertigo of central etiology from vertigo of peripheral etiology. A detailed description of the HINTS exam appears in PubMed in the article published by Kattah JC et al.

    • Head Impulse test: In vestibular disorders that cause vertigo, the head impulse test is often positive.  It is important to rule out lesions of the cervical spine or paraspinal musculature before performing this test. If the examiner is doubtful about the integrity of the neck or the spine, it is best to avoid this test altogether. 
    • The examiner sits across the patient and holds the patient’s head in between both palms. The examiner asks the patient to fix the gaze on the examiner’s nose. The head is rotated slightly laterally about 10-20 degrees to one side. Subsequently, the examiner brings the head back to the primary position in a swift motion while continually observing the patient’s eyes. An individual with an intact vestibular system (and thus an intact vestibular-ocular reflex) can maintain his or her gaze on the examiner’s nose. A corrective horizontal saccade is seen in a patient with unilateral vestibular damage when the head rotates to the primary position from the side with the vestibular lesion. The test is then repeated for the contralateral side.
    • Nystagmus: In comparison to nystagmus of peripheral etiology as described above, the nystagmus of central etiology has the following features:

      • Bi-directional (gaze-evoked): The direction of nystagmus changes with the direction of gaze
      • Central nystagmus may also be vertical, which is uncommon in nystagmus of peripheral etiology.
    • Test of Skew: In lesions involving the brainstem, vertical malalignment of the eyes may present (skew deviation). The alternate cover test can demonstrate this. In this test, the examiner asks the patient to look straight ahead and then alternately covers each eye at a time. If a skew deviation exists, a corrective vertical or oblique saccadic movement is appreciated.
  • If any of the three tests point to a central etiology, the likelihood of a central etiology such as a posterior circulation stroke should merit strong consideration. It is important to note that every test should be taken in the right clinical context and should not be used as the sole criteria to confirm or refute a diagnosis without considering the history, the rest of the neurological exam, and other investigations. 

Scanning speech

  • Cerebellar disorders can cause ataxic speech, also known as scanning speech, where the patient usually breaks words into respective syllables.

Dysmetria 

  • Finger to nose test: This can be tested in the upper limb by having the patient reach out and touch the examiner’s index finger with his or her index finger and then touch his or her nose with the same finger. In a patient with a lesion in the cerebellar hemisphere, the ipsilateral arm will manifest an intention tremor while nearing the target. This tremor occurs due to overshooting or undershooting of the patient’s index finger due to improper coordination of movements.
  • Heel to shin test: For the lower extremities, the examiner asks the patient to move their heel across the shin in a proximal to distal motion. In a hemispheric cerebellar lesion, the patient will not be able to trace the shin in a straight line and will move the heel side to side.

Adiadochokinesia (dysdiadochokinesia) 

  • Patients with cerebellar lesions are unable to execute rapid alternating movements properly. The examiner asks the patient to place the palm on the knee and then perform rapid alternate pronation and supination of the forearm. Affected individuals will have difficulty in executing such alternating movements. The movements will appear jerky and irregular.

Rebound phenomenon 

  • With elbows resting on the legs on the table, the examiner asks the patient to flex the elbows against the examiner’s resistance. The examiner then abruptly stops providing resistance. Unaffected patients can contract the antagonist muscle(triceps) so that there is none to minimal flexion at the elbow. In individuals with cerebellar lesions, there is exaggerated flexion of the ipsilateral elbow due to the failure of timely contraction of the antagonist muscle. This phenomenon often presents exaggeratedly in spastic limbs. Other upper extremity joints can also undergo testing in this fashion with similar results.

Intention tremor :

  • Intention tremor is a kinetic tremor (most prominent when performing a task); the previously mentioned finger to nose test can elicit this sign. The tremor worsens as the patient approaches the examiner’s finger.

Ambulation:

  • Stance and posture: In cerebellar lesions, patients tend to have a broad-based stance. The examiner may notice side to side or back and forth swaying of the body while the patient is standing; this is known as titubation.
  • Gait: The gait in cerebellar lesions is reminiscent of acute alcohol intoxication. The patient tends to stagger or sway side to side and walks with a broad base, known as an ataxic gait.
  • Tandem walk: Individuals with cerebellar lesions are unable to walk in tandem. The test is performed as follows: The examiner asks the patient to walk in a straight line with the heel of the leading foot touching the toes of the lagging foot as if walking on a tightrope. This sign may also be seen in sensory ataxia or vestibulopathy. Thus, it is essential to check for other signs such as the Romberg’s sign to differentiate sensory ataxia or vestibulopathy from cerebellar ataxia.
  • Absence of Romberg’s sign: The examiner asks the patient is asked to stand with eyes open, feet close together, and arms by the side. The patient is then asked to close the eyes. Romberg’s sign is positive if there is disproportionate swaying or patient falling with eyes closed as compared to eyes open. This sign is present in lesions of the sensory afferent pathway or the vestibular system. Excessive swaying, even with eyes open, can be seen in cerebellar lesions.

Hypotonia:

  • Damage to half of the cerebellum can lead to ipsilateral hypotonia.

Cerebellar mutism :

  • If an injury occurs to the central cerebellum, such as from a tumor or surgery, a patient may have mutism for days to indefinitely after the injury.

Cerebellar examinations are mandatory to diagnose exact etiologies.

An important part of cerebellar examinations

  • 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 pseudoarthrosis (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 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)
  • 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

Evaluation

Investigations to find out most likely cause

  • 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

Treatment of Cerebellar Dysfunction

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 levels. Following up with routine laboratory work is essential in these patients to ensure the achievement of therapeutic levels of vitamins.Patients can benefit from rehabilitation, gait training, the 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.

Generally speaking, it is unrealistic to expect that any medication will have a strong effect on most types of cerebellar disturbances because for the most part, these disorders are due to “dead neurons”. Until we have a way to bring the dead back to life (neurons I mean), it seems unlikely that any drug will make much of an impact. This is another way of saying that once the “cows have escaped, it doesn’t do any good to close the barn door”. I call these “barn door” treatments.

4-AP is a cerebellar stimulant, that can be used to treat episodic ataxia type II (yes, many cerebellar disorders, this is just one of them). In our clinic in Chicago, we have had rare success with this medication, probably reflecting the rarity of EA-2. This drug has been written about on many occasions by Dr. Strupp and colleagues (e.g. Strupp et al, 2011).

Riluzole, a treatment for ALS, has been tried in various types of ataxia. Riluzole is intended to slow down the rate of cell death. One would not think that it would bring neurons back to life — this is a “close the barn door after the cows have escaped” type treatment. Nevertheless, Romano and colleagues reported improvement in roughly 68% of treated patients after 8 weeks, compared to 5% of the placebo group(Ristori et al, 2010; . This amazing result needs to be replicated by another group.

Varenicline (Chantx) was studied for SCA-3 (Zesiewicz et al, 2012). Chantix is a partial nicotinic receptor drug approved for smoking cessation. This drug was reported to improve cerebellar function in a study of 20 patients. Again, this is a “barn door” treatment.

TRH has been reported in several small studies as well as some larger ones to improve cerebellar function (e.g. Wang and Chiu, 1991). This treatment is not “main stream”, in spite of its very long history. We do not think it works.

Vestibular rehabilitation treatment may be helpful in that patients can be made aware of their limits and abilities, and given access and knowledge concerning walkers, canes, and related appliances. Axial weight loading has been tried in cerebellar ataxia, but effects are inconsistent (Clapton et al, 2003)

TMS treatment is being experimented with, but results are not yet back. It would be difficult to understand how TMS could make neurons grow back. Another word, another “barn door” treatment.

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

References

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