What is Cerebellar Agenesis?

By Syed S. A.Reviewed by Sophia Coveney

Causes and symptoms
Epidemiology
Case report
Diagnosis and treatment
References
Further reading

Cerebellar agenesis is a condition in which the normal formation of the hindbrain is disrupted. Patients with this disorder have very few pieces of cerebellar tissue - frequently the remains of lower cerebellar peduncles, anterior vermal lobules, and flocculi.

Both genetically mediated and disruptive causes can cause cerebellar agenesis (CA). Cerebellar agenesis can manifest itself in various ways, with symptoms ranging from mild to severe.

Cerebellar agenesis affects not only physical abilities but also cognitive abilities, linguistic impairments, and affective issues.

Causes and symptoms

Cerebellar agenesis is caused by a variety of factors (heterogeneous). Cerebellar damage caused by bleeding, lack of or decreased blood flow (ischemia), or other conditions are acquired (prenatal/perinatal) causes.

Cerebellar agenesis (CA) can be caused by both genetically mediated and disruptive causes. CA can be caused by a genetically mediated pathomechanism (e.g., mutations in the pancreatic transcription factor 1 gene, PTF1) or a disruption (e.g., intrauterine/neonatal damage with the disappearance of the developing cerebellum).

Sener used the phrase "vanishing cerebellum" to describe cerebellar disruptive lesions in children with Chiari II malformation. Prenatal hindbrain herniation through the foramen magnum can induce parenchymal injury, resulting in the resolution of a portion of the cerebellum (usually asymmetric). The cerebellum vanishes totally in disruptive CA due to direct or indirect damage.

Cerebellar agenesis can manifest itself in various ways, depending on the person. According to the medical literature, some people with cerebellar agenesis have only modest symptoms. It has been suggested that motor performance may be nearly normal in some cases, possibly due to partial compensation from other brain areas.

Individuals with cerebellar agenesis whose mental capacities were undamaged and who did not exhibit any symptoms of cerebellar agenesis have also been reported (asymptomatic cases). Cerebellar agenesis most likely represents a spectrum of diseases ranging from severe disability to milder manifestations of the disorder.

Earliness, localization, and degree of cerebellar agenesis appear to be linked to the severity and range of motor, cognitive, and psychiatric deficits. Patients with congenital anomalies have more severe and less specific impairments than those who develop cerebellar lesions later in life.

Patients with phylogenetically more ancient structures involved (complete or partial cerebellar vermis agenesis) have a more severe clinical picture. This includes severe, pervasive impairments in social and communication skills (autism or autism-like behavior), behavior modulation (self-injury and aggressiveness), and a marked delay in language acquisition, especially in language comprehension.

When lesions are limited to phylogenetically more recent structures, such as the cerebellar hemispheres, the clinical picture is marked by minor cognitive impairment or borderline IQ, adequate social functioning, context adjustment abilities, and a better prognosis.

Epidemiology

Cerebellar agenesis is extremely uncommon, with only a few documented cases. CA appears to afflict both men and women in about equal percentages.

The disorder's exact frequency and prevalence in the general population are unknown. The occurrence of congenital solitary cerebellar agenesis is extremely unusual.

Case report

In 2020, Dennison et al. described a case of cerebellar agenesis recently encountered and diagnosed in Orlando, Florida, United States. At 37 weeks and two days, a 25-year-old mother gave birth to a 5 lb 11 oz, somewhat preterm child via C-section.

Polyhydramniosis and a positive chlamydia test during early pregnancy affected the pregnancy, which later tested negative after therapy. The fetus was breech at birth, necessitating a cesarean section.

The amniotic fluid was stained with meconium, and the umbilical cord was found to be short. The infant was microcephalic, hypertonic, and spastic at birth and was in significant respiratory distress with irregular breathing.

At one and five minutes after birth, the APGAR scores were 5/10 and 7/10, respectively. The infant's breathing problems persisted, necessitating an emergency transfer to the newborn intensive care unit (NICU), where they were put on continuous positive airway pressure (CPAP).

The infant was hypertonic and had excessive deep tendon reflexes, according to a medical assessment performed in the NICU. All primitive reflexes were missing, including Moro, rooting, and sucking. A systolic cardiac murmur of grade I to II was also present in the baby. Bilaterally, coarse breath sounds were heard.

The infant had twitching and spastic motions during their time in the NICU. The infant had echocardiography on day one of life, which revealed a massive, bidirectional patent ductus arteriosus.

A patent foramen ovale with left-to-right shunting was also present. Because of the aberrant neurological test, a brain computed tomography was performed, which revealed that the cerebellum was almost completely absent, with only traces of the cerebellar hemispheres and vermis remaining.

There was also partial corpus callosum agenesis and extensive cerebral and brain stem atrophy. Brain magnetic resonance imaging (MRI) verified these results, prompting additional neurological testing.

During waking and sleep, continuous electroencephalography indicated significantly aberrant background activity with burst suppression and extended clusters of infantile spasms, consistent with early infantile epileptic encephalopathy (also known as Ohtahara syndrome).

Topiramate was prescribed for the infant's epileptic activity, considerably reducing symptoms. The infant had a tracheostomy and a gastrostomy tube before being discharged. The infant's spasms persisted despite a visit to the neurology department, although they showed modest improvement following a course of high-dose steroids.

To date, follow-up electroencephalography has revealed that epileptiform discharges have persisted. The infant's spastic quadriplegia remained severe, necessitating a ventilator and g-tube.

The infant experienced sudden cardiac arrest at six months of age and was brought to a hospital after multiple rounds of cardiopulmonary resuscitation and recovery of spontaneous circulation. The infant was eventually declared brain dead, and life support was turned off.

Diagnosis and treatment

Diagnosis is largely based on the neuroimaging findings of MRI. Regarding diagnosis, prognosis, and genetic counseling, it is also critical to distinguish cerebellar disturbances from cerebellar abnormalities.

The treatment for cerebellar agenesis focuses on the specific symptoms that each person experiences. Collaboration with a group of professionals might be necessary for treatment. Pediatricians, neurologists, speech pathologists, and other healthcare specialists may be required to organize an affected child's treatment methodically and completely.

Early intervention is critical for children with cerebellar anomalies to achieve their full potential. Physical therapy, occupational therapy, and speech therapy are some of the services that may be effective.

Special remedial schooling may be beneficial to some youngsters. Individuals with major motor deficiencies or speech issues may benefit from adaptive equipment.

References

• Dennison JV, & Tailor DR (2020). Cerebellar Agenesis: A Case to Remember. Journal of Pediatric Neurology, 18(01), 045–048. doi:10.1055/s-0039-1679892. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0039-1679892
• Poretti A, Risen S, Meoded A, et al. (2013). Cerebellar agenesis: an extreme form of cerebellar disruption in preterm neonates. Journal of Pediatric Neuroradiology, 2(2), 163-167. doi:10.3233/PNR-13060. https://content.iospress.com/articles/journal-of-pediatric-neuroradiology/pnr060
• Romaniello R, & Borgatti R. (2013). Cerebellar Agenesis. In: Manto M., Schmahmann J.D., Rossi F., Gruol D.L., Koibuchi N. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Dordrecht. doi:10.1007/978-94-007-1333-8_84. https://link.springer.com/referenceworkentry/10.1007/978-94-007-1333-8_84
• Cerebellar Agenesis - NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). (2018). Retrieved 24 January 2022, from https://rarediseases.org/rare-diseases/cerebellar-agenesis/.