Cerebellar Disorders

Timothy C. Hain, MD Page last modified: November 21, 2009

This page is meant to provide a general outline of cerebellar disorders. More specific and detailed material is found in links.

The cerebellum with surrounding skull and spinal fluid occupies the bottom 1/3 of this axial MRI image.

What is the cerebellum and what does it do ?

The cerebellum is part of the brain. It lies under the cerebrum, towards the back, behind the brainstem and above the brainstem. 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.

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.

Laboratory diagnosis of Cerebellar Disorders

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.

Brain Imaging
Brain imaging is always obtained in cerebellar disorders. MRI imaging, with the highest filed 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 saggital 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, neverthless 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.

Disorder Stroke or Multiple Sclerosis Paraneoplastic cerebellar degeneration Tumors Toxins such as ethanol, phenytoin, or chemotherapy. Chiari Malformation Olivopontocerebellar atrophy

Brain imaging in cerebellar disorders, subcategorized by timing of sympto Finding Conditions with a sudden onset High-signal in cerebellar hemisphere or brainstem Conditions with gradual progression over months No MRI findings Mass in cerebellum

Atrophy of the cerebellar hemispheres. Chronic alcoholism is Slowly progressive or hereditary conditions Displacement of cerebellar tonsils below foramen magnum Ballooning of the IV ventricle

Atrophy of vermis, hemispheres, brainstem. Large IV ventricl

OPCA with slow saccades

"Molar tooth" deformity due to severe atrophy of the pons "Fine comb" atrophy of cerebellum

OPCA -- recessive Friedreich's Ataxia

Lateral cerebellar atrophy with "Fish mouth" deformity due to cerebellum. Cervical spinal cord atrophy about 50% reduced area Small Medulla

FXTAS

High signal in the middle cerebellar peducles. Most common

Differentiating cerebellar from vestibular disorders

There sometimes are difficulties in using clinical findings to separate out cerebellar from inner ear disturbances. For example, bilateral vesibular 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.

Sources of cerebellar injuries

Toxins (ethanol, chemotherapy, anticonvulsants). Autoantibodies (paraneoplastic cerebellar degeneration , autoimmune disorders) Structural lesions (strokes, MS, tumors, etc) Inherited cerebellar degenerations

Toxins
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

Autoantibodies:
The cerebellum may be injured by autibodies or other immune system disturbances such as in the paraneoplastic cerebellar degenerations and in celiac disease (Gluten enteropathy). There is considerable evidence for the existence of gluten related neurological syndromes ( Hadjivassiliou, Grunewald et al. 2002; Hadjivassiliou, Grunewald et al. 2003). Hadjivassiliou suggests that gluten intolerance related ataxia is the single most common cause of a sporadic ataxia, accounting for about 41% of cases. Anti gliaden-antibody testing can be used to detect these cases.Others differ strongly. They observe that 10% of the otherwise normal population has anti-gliaden antibodies, which would suggest a very high rate of false-positives would be expected. (Willis and Unsworth, 2002). It seems to us that the more conservative opinion is more likely to be correct, but nevertheless a gluten-free diet should reasonably be tried in persons who have no other cause for 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): 68591. 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

Structural lesions of the cerebellum (under construction). Strokes

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.

Multiple Sclerosis affecting the cerebellum

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).

Tumors of the cerebellum

Axial and Saggital 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 on the site DVD: 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.

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.

Saggital 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:

vermal resection

Congenital cerebellar anomalies

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 ArnoldChiari 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 communicationg 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).

Inherited cerebellar degenerations:

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.

Miscellaneous causes:
superficial siderosis Recurrent bleeding on the surface of the brain may cause "superficial siderosis", which is typlified by bilateral sensorineural deafness and cerebellar ataxia with dysarthria and nystagmus (Fishman, 1993). Superficial siderosis can rarely occur as a complication of brachial plexus avulsion (Fearnley et al, 1995). 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.

Fearnley J, Stevens J, Rudge P. Superficial siderosis of the central nervous system. Brain 1995:118:1051-1066 Fishman RA. Superficial siderosis. Ann Neurol 1993:34:635-636 Watanabe, M., et al., [A case of superficial siderosis of the central nervous system with bilateral vestibular dysfunction]. No To Shinkei, 1997. 49(10): p. 931-5.

Miller-Fisher

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.

TREATMENT
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. 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)