Timothy C. Hain, MD Page last modified: April 22, 2019
This page is meant to provide a general outline of cerebellar disorders. More specific and detailed material is found in links.
See: ataxia telangiectasia•CANVAS•chiari•episodic-ataxia•fragileX•friedreichs•pcd•sca•VHL
|The cerebellum with surrounding skull and spinal fluid occupies the bottom 1/3 of this axial MRI image. This is an axial view, through the middle of the cerebellum above, also showing some of the temporal lobe.||Artists rendition of human brain, showing location of cerebellum. (from Science Trends)|
The cerebellum is part of the brain. It lies under the cerebral cortex, towards the back, behind the brainstem and above the spinal cord. The cerebellum is largely involved in "coordination". Persons whose cerebellum doesn't work well are generally clumsy and unsteady. They may look like they are drunk even when they are not.
The cerebellum contains a lot of neurons. According to Hurculano-Houzel (2010), it contains about 80% of the neurons in the brain. So small in size, large in number. It must be doing something pretty important. The large neuron count probably is due to the more elaborate folding of the cerebellar cortex, as the neurons are mainly close to the periphery.
Cerebellar disorders are rare. They are often called "ataxias". According to Musselman et al (2014), the prevalence of childhood ataxia is 26/100,000 children. Ataxia is rare compared to cerebral palsy (211/100,00) and autism (620/100,000).
Many cerebellar disorders are genetic in origin. In general, prevalance of genetic disorders and especially autosomal recessive disorders is much higher in populations where there is more consanguinity. Examples of this include Quebec, Canada and the Al-Kharga district in Egypt. There are also many acquired cerebellar disorders. For example, drinking too much alcohol for a long time causes a cerebellar disorder.
Diagnosis of Cerebellar disorders
The main clinical features of cerebellar disorders include incoordination, imbalance, and troubles with stabilizing eye movements. There are two distinguishable cerebellar syndromes -- midline and hemispheric.
Midline cerebellar syndromes are characterized by imbalance. Persons are unsteady, they are unable to stand in Romberg with eyes open or closed, and are unable to well perform tandem gait. Severe midline disturbance causes "trunkal ataxia" a syndrome where a person is unable to sit on their bed without steadying themselves. Some persons have "titubation" or a bobbing motion of the head or trunk. Midline cerebellar disturbances also often affect eye movements. There may be nystagmus, ocular dysmetria and poor pursuit.
Hemispheric cerebellar syndromes are characterized by incoordination of the limbs. There may be decomposition of movement, dysmetria, and rebound. Dysdiadochokinesis is the irregular performance of rapid alternating movements. Intention tremors may be present on an attempt to touch an object. A kinetic tremor may be present in motion. The finger-to-nose and heel-to-knee tests are classic tests of hemispheric cerebellar dysfunction. While reflexes may be depressed initially with hemispheric cerebellar syndromes, this cannot be counted on. Speech may be dysarthric, scanning, or have irregular emphasis on syllables.
The diagnosis of a cerebellar disorder is usually made by a neurologist, and is usually straightforward, due to the high specificity of the signs described above.
ENG or rotatory chair testing may show specific signs of a cerebellar disorder. In general, one must be very careful in using these studies as the audiologists who commonly interpret ENG tests, generally are unfamiliar with central disorders, and often simply say that the patient has a "central vestibular disorder", rather than indicate that they don't find anything wrong with their patient's ears. More about cerebellar signs in the saccadic portions of the ENG/rotatory chair test is found here.
Genetic testing in sporadic ataxia (i.e. with no family history) is very low yield. According to Giordano et al (2017), it yields a diagnosis in only 6%. Given the high cost and low benefit of genetic testing, we think most will choose not to do this. When it is possible to edit genes, this equation will change.
Brain imaging is always obtained in cerebellar disorders. MRI imaging, with the highest field strength that is available, should be undertaken. We do not recommend "open MRI" testing in MRI's, or "low field". At the present writing - -2008 -- we recommend 3T MRI testing, preferably with T1, T2, diffusion, and Flair. T1 sagittal images must be obtained to diagnose the Chiari malformation.
In general, MRI scanning often shows shrinkage of part or all of the cerebellum and/or shrinkage of the brainstem. While great progress has been made recently in the identification of genetic causes of cerebellar atrophy, nevertheless the most common situation is for genetic testing (if available) to be negative. This means that genetic testing is frequently unhelpful, and the role of cerebellar genetic testing should not be overemphasized. Some general references about radiological diagnosis are Huang, Tuason et al. 1993; Wullner, Klockgether et al. 1993.
Because genetic testing is usually negative in progressive cerebellar disorders, the "diagnosis" of cerebellar disorders basically means separation of patients into overlapping groups -- genetically identified degenerations, progressive hereditary conditions without an identified gene, and undiagnosed causes of cerebellar symptoms. Generally the "undiagnosed" group is the largest one.
Broadly speaking, there are many disorders that cause shrinkage of the cerebellum -- such as hereditary degenerations or toxins. There are very few disorders that cause shrinkage of the brainstem - -these are mainly hereditary degenerations. Severe cerebellar symptoms with a normal MRI scan suggest a paraneoplastic cerebellar problem.
Conditions with a sudden onset
|Stroke or Multiple Sclerosis||High-signal on MRI in cerebellar hemisphere or brainstem|
Conditions with gradual progression over months
|Paraneoplastic cerebellar degeneration||No MRI findings|
|Tumors||Mass in cerebellum|
|Toxins such as ethanol, phenytoin, or chemotherapy.||Atrophy of the cerebellar hemispheres. Chronic alcoholism is associated mainly with vermal atrophy.|
Slowly progressive or hereditary conditions
|Chiari Malformation||Displacement of cerebellar tonsils below foramen magnum|
|Olivopontocerebellar atrophy (also see SCA)||Atrophy of vermis, hemispheres, brainstem. Large IV ventricle|
|OPCA with slow saccades||
Ballooning of the IV ventricle
"Molar tooth" deformity due to severe atrophy of the pons
"Fine comb" atrophy of cerebellum
|OPCA -- recessive||Lateral cerebellar atrophy with "Fish mouth" deformity due to loss of tertiary and secondary folia of cerebellum.|
Cervical spinal cord atrophy about 50% reduced area
|FXTAS||High signal in the middle cerebellar peducles. Most common hereditary cerebellar syndrome.|
There sometimes are difficulties in using clinical findings to separate out cerebellar from inner ear disturbances. For example, bilateral vestibular loss can be sometimes confused with cerebellar disorders. Otologic testing -- ENG or VEMP -- usually makes this distinction quite easy however. Also, cerebellar patients are usually more unsteady than patients with inner ear conditions.
There are a large number of processes that injure the cerebellum. Ethanol and many anticonvulsant medications (such as phenytoin and carbamazepine) are cerebellar toxins. Ethanol characteristically causes atrophy of the cerebellar vermis. This is true even for exposure in utero (Autti-Ramo et al, 2002).
Certain types of cancer chemotherapy, such as cytosine arabinoside (Zawacki et al, 2000), are cerebellar toxins. Lithium, given for manic-depressive disorder, is a cerebellar toxin.
- Zawacki et al. Cerebellar toxicity of cytosine arabinoside: clinical and neuropsychological signs. Neurology 55, 1234, 2000
- Diego et al. Vestibular and hearing manifestations of phenytoin toxicity: a retrospective review. ENT journal, 80, 404-409, 2001
The cerebellum may be injured by antibodies or other immune system disturbances such as in the paraneoplastic cerebellar degenerations and in celiac disease (Gluten enteropathy). See this page for a review about gluten associated ataxia.
These paraneoplastic syndromes are accompanied by abnormal blood tests for antibodies directed against neurons. The most common tumors are of the lung and breast. Only about 1% of all persons thought to have a paraneoplastic syndrome turn out to have antibodies (Pittock et al; 2004). Often a person who has one particular antibody also has others, suggesting that individual antibodies are not associated with individual conditions.
The cerebellar MRI in persons with paraneoplastic syndromes is generally completely normal.
- Greenlee JE. Cytotoxic T Cells in Paraneoplastic Cerebellar Degeneration. Ann Neurol 2000: 47:4-5
- Hadjivassiliou and others. The humoral response in the pathogenesis of gluten ataxia. Neurology 2002:58:1221-26
- Hadjivassiliou, M., R. Grunewald, et al. (2003). "Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics." Brain 126(Pt 3): 685-91.
- Pittock SJ and others. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004:56:715-719
- Willis AJ, Unsworth DJ. The neurology of gluten sensitivity: separating the wheat from the chaff. Curr Opin Neurol 2002:15:519-523
|There are three main arteries that supply the cerebellum -- the SCA (superior cerebellar artery), the AICA (Anterior inferior cerebellar artery), and PICA (posterior inferior cerebellar artery)|
There are many potential processes that can injure the cerebellum. Strokes are probably the most common. Because the cerebellum is supplied by three major arteries on each side (SCA or superior cerebellar artery, AICA or anterior inferior cerebellar artery, and PICA or posterior inferior cerebellar artery), there are many potential stroke syndromes to consider. The most common syndrome is that if the PICA, also called "Wallenberg's syndrome", or "lateral medullary syndrome". The second most common is the AICA syndrome, and the least frequent is SCA.
Vascular malformations such as cerebellar hemangioblastoma are also fairly common.
Strokes that bleed into the cerebellum, usually hypertensive, can be life threatening and may require surgical decompression. An example of abnormal eye movements from a pontine cavernoma is found here.
|This patient with MS has a plaque in her right middle cerebellar peduncle (which is on the left side of this axial MRI). Note that the 8th nerve, cochlea and labyrinth can be seen on the right side of the picture. This patient was dizzy and also had poor pursuit.|
Multiple sclerosis is another fairly common source of cerebellar disorder. MS often involves the cerebellar connections in the brainstem, and particularly the middle cerebellar peduncle (see above).
|Axial and Sagittal views of cerebellum with metastatic tumor from breast involving the vermis. The tumor is the white irregular area in the center of each picture. This patient had profound saccadic dysmetria.|
Supplemental material : Video of saccadic dysmetria (same patient as above).
There are a large number of tumors that can either metastasize to the cerebellum (such as lung or breast cancer), or arise in the cerebellum itself (such as cerebellar astrocytoma or medulloblastoma). The medulloblastoma arises in the cerebellar nodulus, and because of this critical location, often presents with dizziness in addition to hydrocephalus.
|Sagittal view of patient who had a medulloblastoma surgically removed. The large hole in the middle of the cerebellum is where the tumor used to be. This patient was very unsteady and had strong positional nystagmus due to removal of her cerebellar nodulus.|
Patients who have had medulloblastomas surgically removed usually continue to have measurable abnormalities in central vestibular processing -- see figure above (Hain et al, 1988).
|Cerebellar hemangioblastoma with hydrocephalus.|
|Axial cerebellar hemangioblastoma.||Sagittal cerebellar hemangioblastoma|
The patient whose MRI is shown above presented with dizziness, unsteadiness and headaches. His examination showed a modest positional nystagmus, as well as papilloedema. There was no saccadic dysmetria. After the papilloedema was noticed, he had an MRI done and was admitted immediately for neurosurgery. The tumor was not locally invasive, but rather was separable from the cerebellum, and the patient had very little residual.
This case illustrates why it is is occasionally critical that patients with dizziness of unknown cause see a neurologist.
Other illustrative cases:
|Patient with congenital absence of one cerebellar hemisphere. Very few if any physical findings attributable to the missing half cerebellum.||Patient with an Arnold Chiari Malformation. This patient had dizziness, downbeating nystagmus and poor pursuit.|
Congenital malformations may involve the cerebellum also. The most common is the Arnold-Chiari malformation (shown above), which is a condition where the cerebellar tonsils are displaced downward with respect to the skull. Basilar impression and platybasia are closely related malformations.
Probably second most common are various types of agenesis syndromes. In the Dandy-Walker syndrome (not to be confused with "Dandy's" syndrome, indicating bilateral vestibular loss), there is partial or complete agenesis of the cerebellar vermis, cystic formation of the posterior fossa communicating with the fourth ventricle, and hydrocephalus. About 80% of the diagnoses of Dandy-Walker are made by the age of 1 year of age. Dandy Walker is often accompanied by other malformations, the most common of which is agenesis of the corpus callosum.
Of the numerous syndromes in which there is vermal agenesis, according to Bordarier and Aicardi (1990), only Goldenhar's syndrome is associated with deafness (pre-auricular tags, mandibular dysostosis, deafness, corneal fibrolipoma).
While cerebellar "arachnoid cysts" are typically thought to be benign, our experience is that they are often associated with floccular type gaze holding abnormalities (see image below and this link on gaze-evoked nystagmus).
|MRI of midline lesion thought to be arachnoid cyst, associated with gaze-evoked nystagmus (courtesy of Dr. Dario Yacovino).|
There are a large number of rare but well described inherited cerebellar disorders. These generally go under the names of Freidreich's ataxia, spinocerebellar atrophy, and olivo-ponto cerebellar atrophy. See this link for more information.
Recurrent bleeding on the surface of the brain may cause "superficial siderosis", which is typified by bilateral sensorineural deafness and cerebellar ataxia with dysarthria and nystagmus (Fishman, 1993). Superficial siderosis can also cause bilateral vestibular loss (Watanabe, 1997), which can cause ataxia resembling that of a cerebellar disorder. Superficial siderosis is diagnosed through MRI.
This is a rare disorder related to Guillain Barre, characterized by a combination of ataxia, weakness or paralysis of the eye movements, and peripheral neuropathy. Most patients present with diplopia and eventually develop complete paralysis of their eyes. Antibodies to the ganglioside GQ1b are associated with Miller Fisher syndrome. This condition should be considered when there is a combination of diplopia, ataxia, and loss of deep tendon reflexes. The ataxia is probably due to loss of sensory input to the cerebellum. Mean time of recovery is at 10 weeks.
Patients with cerebellar disturbances are generally highly unlikely to benefit from medication or therapy. Nevertheless, these patients are usually so impaired, that it seems ill advised not to try out all possible modalities. When specific treatments are available, such as in the Arnold Chiari malformation, they are used when the risk of treatment appears less than leaving the condition alone.
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 words, another "barn door" treatment.