Tuesday, November 19, 2019

Cerebellar agenesis

Yu F, Jiang QJ, Sun XY, Zhang RW. A new case of complete primary cerebellar agenesis: clinical and imaging findings in a living patient. Brain. 2015 Jun;138(Pt 6):e353.

We read with great interest the articles previously published in Brain by Glickstein (1994) and Boyd (2010) describing the clinical evidence and review of cerebellar agenesis. Here we report a new case of a living patient whom we believe to be another patient with cerebellar agenesis. Cerebellar agenesis is an extremely rare condition implying complete absence of the cerebellum. The pathogenesis and molecular basis of this disease remain unknown. There are very few reported cases of complete cerebellar agenesis, making it challenging and controversial to understand the degree of cerebellum development necessary to avoid deficits in motor and non-motor functions. Further, a detailed description of neurological findings in a living adult with cerebellar agenesis is almost non-existent; most cases are reported based on autopsy reports. The patient presents with mild mental impairment and medium motor deficits. CT and MRI scans revealed no remnants of any cerebellar tissues, verifying complete absence of the cerebellum. A comprehensive literature review reveals novel implications for differential diagnosis. We conclude that primary cerebellar agenesis is actually the same diagnosis as Chiari malformation IV.

A 24-year-old female patient was admitted to hospital complaining of dizziness and the inability to walk steadily for more than 20 years, and nausea and vomiting for 1 month. She is married with a daughter, and her pregnancy and delivery were described as uneventful. Her parents had no history of neurological disorders. Her four sisters and one brother are described as neurologically normal. According to her mother, she was 4 years old before she could stand unassisted, and did not begin to walk unassisted until the age of 7, with a persistently unsteady gait. She never ran or jumped. Her speech was not intelligible until 6 years of age and she did not enter school. A neurological examination revealed she could cooperate and fully orientate. A verbal analysis test revealed her word comprehension and expression remained intact and she had no sign of aphasia, but mild to moderate signs of cerebellar dysarthria. The patient has mild voice tremor with slurred pronunciation and her voice quality is slightly harsh. Cerebellar ataxia including Romberg’s sign, and there is evidence of heel-knee-tibia impairment. The patient experienced mild to moderate dysmetria in reaching the nose when administered the finger-to-nose test. Pronation-supination alternating movements were slightly irregular and slowed. While she is able to walk unsteadily without support, her gait is moderately unsteady. The patient has evidence of tandem gait and moderately reduced gait speed. There is no focal paresis but the muscle tone is mildly increased. Evaluation of the sensory system showed no abnormalities, no deformities of the fingers and toes were observed, and her complete blood count and urinalysis were normal.

The patient has low posterior fossa density and no cerebellar tissue following CT analysis [A]. No recognizable cerebellar structures are present, and the posterior fossa was filled by CSF when analysed by cranial MRI [B]. The mesencephalon, pons, and medulla oblongata were present. The mesencephalon had a normal aspect, and the aqueduct of Sylvian seemed patent. The pons was hypoplastic, due to volume reduction of the pontine prominence. The medulla oblongata was attenuated and no hindbrain herniation was detected. A membranous structure present at both lateral sides of the pons formed a large cyst, which occupied most of the normal-sized posterior fossa. Tentorial attachment and straight sinus were normal, as was the pattern of cortical gyri, the corpus callosum, the cerebral peduncle and aqueduct. The shape and relative proportions of the third ventricle and lateral ventricle were preserved with no hydrocephalus. In addition to CT and MRI findings, magnetic resonance angiography also demonstrated vascular characteristics of this patient consistent with complete cerebellar agenesis. The posterior inferior cerebellar artery, anterior inferior cerebellar artery and superior cerebellar artery were absent bilaterally, indicating an avascular posterior fossa. The basal artery, posterior cerebral artery and their branches were normal. Complete lack of the efferent and afferent limbs of the cerebellum was diagnosed by diffusion tension imaging analysis
With these findings, the patient was diagnosed with complete primary cerebellar agenesis...

Primary cerebellum agenesis, a rare condition marked by absence of the cerebellum, was first described by Combettes (1831). Only eight living cases have been reported prior to this study. The clinical presentation of primary cerebellum agenesis varies from degrees of cerebellar dysfunction and developmental delay at an early age. Oftentimes, primary cerebellum agenesis is diagnosed as Chiari malformation type IV, a condition defined by an incomplete or underdeveloped cerebellum. Primary cerebellum agenesis is associated with severe developmental anomies resulting in a high mortality rate; few reports on the subject have been published. The 24-year-old female we report, with mild mental retardation and cerebellar ataxia, was diagnosed with complete primary cerebellar agenesis based on CT and MRI scans. This patient presents with complete cerebellum agenesis with a complete lack of the efferent and afferent limbs of the cerebellum, a relatively normal-sized posterior fossa, a normal brain and spine without syringomyelia or encephalocele. This case is the ninth reported case of this diagnosis...

Most individuals with complete primary cerebellar agenesis are infants or children with severe mental impairment, epilepsy, hydrocephaly and other gross lesions of the CNS. In even more rare instances, adults have been discovered with apparent complete primary cerebellar agenesis, but detailed neurological descriptions of these findings in a living adult are lacking. Complete primary cerebellar agenesis diagnosis usually occurs by autopsy. Cerebellar deficiency arises very early in embryogenesis and the developmental plasticity and functional compensation with the remaining brain tissue is remarkable. In our case, complete absence of the cerebellum results in only mild to moderate motor deficiency, dysarthria and ataxia, although clearly present, were less than would be expected in completely absence of the cerebellum. This surprising phenomenon supports the concept of extracerebellar motor system plasticity, especially cerebellum loss, occurring early in life. In this series of nine living cases, three patients were male, six female. One patient was noted of consanguinity whereas others had no family history of genetic disorders and their siblings were reported as neurologically normal. All patients were related with uneventful pregnancy and delivery and blood count, chemistry and serological test were normal. Only one patient was completely normal in neurological examinations (three mental development normal). The other eight patients all showed cerebellar symptoms from motor, language to mental development...

The vascular changes induced by cerebellum malformations are not well characterized, and few data are available addressing the effect of complete primary cerebellum agenesis on the vascular system. Pascual-Castroviejo (1978) reported his study of arterial changes in different types of cerebellar defects and found that the posterior inferior cerebellar artery was hypoplastic or aplastic in a large number of cases. In cases of extremely severe cerebellar malformation with almost complete agenesis of the vermis and the hemispheres, the circulation is quite poor and the posterior fossa arteries are very thin. In this case, we find that all of the posterior circulation blood vessels, including the bilateral posterior inferior cerebellar artery, anterior inferior cerebellar artery and superior cerebellar artery, are completely defected. The conclusion that the severity of the posterior fossa’s vascular alterations is directly related to the degree of cerebellar hypoplasia, may be reasonable. At least, our case demonstrates this fact...

Congenital conditions that affect the cerebellum are not uncommon, the most common forms being the Dandy-Walker malformation and the Chiari malformation. Therefore, the differential diagnosis of primary cerebellum agenesis includes these two malformations. Dandy-Walker is easily diagnosed on the basis of the classic triad: (i) complete or partial agenesis of the vermis; (ii) cystic dilation of the fourth ventricle; and (iii) enlarged posterior fossa, with upward displacement of the transverse sinuses, tentorium and torcula. Also it may be accompanied by other developmental anomalies such as callosal agenesis, but the brainstem is normal. Chiari malformation, subdivided into four types, is a common malformation of the brain where the cerebellum protrudes into the spinal canal, causing many symptoms, mostly due to obstruction of CSF outflow. Type I, typically difficult to diagnose and not apparent oftentimes until adulthood, refers to elongation of the cerebellar tonsils forcing protrusion through the base of the skull. Type II includes the herniation of the cerebellar vermis, brainstem and fourth ventricle through the foramen magnum, associated with myelomeningocele and multiple brain anomalies. Hydrocephalus and syringomyelia are common, and the posterior fossa is often small. Type III, the most severe form of hindbrain herniation, covers cases with herniation of the cerebellum and brainstem into posterior encephalocele. Type IV is an extremely rare condition with few patients reported in the literature. It is characterized by loss of cerebellar development, hypoplasia, and reduced cerebellum size. It may occur as a rare autosomal recessive disease. Considering the previous descriptions of anatomical changes related to Chiari malformation IV, it is our opinion and conclusion that it actually represents primary cerebellar agenesis.


  1. A three year-old boy who was born with key parts of the brain either missing or severely atrophied has doctors stumped as he continues to progress far beyond what medical science says a person in his condition should be capable of achieving.

    According to AOL News, Chase Britton was born prematurely three years ago, and is legally blind. He was a year old when suspicions of cerebral palsy caused doctors to perform an MRI on his brain. What they found was astonishing.

    Chase appeared to have no cerebellum, the part of the brain that controls motor skills, balance and emotions. He also appeared to be missing his pons, the part of the brain stem that controls basic functions such as sleeping and breathing. The brain scans showed only fluid where the cerebellum and pons should have been.

    “That’s when the doctor called and didn’t know what to say to us,” said Heather Britton in a telephone interview with AOL from her home in New York. “No one had ever seen it before. And then we’d go to the neurologists and they’d say, ‘That’s impossible.’ ‘He has the MRI of a vegetable,’ one of the doctors said to us.”

    But Chase is not a vegetable at all. Despite the doctor’s dismal prognosis, Chase is managing to do many things that he shouldn’t be able to do without a cerebellum – such as sit up on his own and crawl. Now he’s even learning how to walk.

    “He keeps going,” his mom said. “He keeps picking up new things and progressing. We call it, ‘Chase pace.'”

    “There are some very bright, specialized people across the country and in Europe that have put their minds to this dilemma and are continuing to do so, and we haven’t come up with an answer,” Dr. Adre du Plessis, chief of Fetal and Transitional Medicine at Children’s National Medical Center in Washington, D.C., told Fox News affiliate WGRZ.

    “So it is a mystery.”

    Even more baffling is the fact that Heather had several ultrasounds during her pregnancy and the images clearly show that Chase had a cerebellum at one time.

    “That is actually a fundamental part of the dilemma,” du Plessis told WGRZ. “If there was a cerebellum, what happened to it?”

    Doctors have found no signs of a brain bleed, hemorrhage or stroke, and no damage to any other part of his brain, Britton said. Technically, his diagnosis is cerebellar hypoplasia, which normally means a small cerebellum rather than a missing one.

    Some doctors, such as Steven Novella, M.D., assistant professor of Neurology at Yale University School of Medicine and author of the popular NeuroLogica blog, say Chase’s cerebellum is more than likely atrophied to the point of not being easily visible on an MRI scan. He believes there is probably a remnant there, which explains why the child has the capacity that he does. (continued)

  2. (continued)“The pons also cannot be missing,” Dr. Novella writes. “That’s like saying someone’s neck is missing. It is just atrophied – perhaps the ventral pons is missing or atrophied.”

    From what he could see from videos, Chase’s degree of neurological function appears to be in line with these anatomical deficits. “He can move, but he has very poor coordination. He walks with a walker, and does not seem to have the balance to walk without assistance. He is also legally blind.”

    Dr. Novella believes the most amazing part of Chase’s story has more to do with how well he is able to function with his limitations.

    ” . . . (W)e can be uplifted by the courage and strength of Chase’s parents, who seem to be meeting this challenge with optimism and a very productive ‘can do’ attitude,” he writes.

    His parents have indeed created an optimal environment for Chase. They are providing him with specialized education, a team of therapists that have been working with him since he was an infant, and a special “sensory room” at home which is full of lights and sounds and tactile things — like mirrors — to visually stimulate him. They are also planning to begin horseback-riding therapy.

    “We’re throwing as much at him as possible to make sure he’s as stimulated as possible,” she explained.

    “He’s happy. We call him the Little Gremlin. He loves to play tricks on people. He loves to sing. His goal in life is to make people smile. He’s got so much love around him. We’re an extremely happy family. His story is not tragic.”

    Her message to other parents who might be experiencing medical challenges with their children is “don’t give up on your kids” and “don’t believe everything the doctors say” because “they can be wrong.”

    “People could view this as a tragic story. But that depends on how you look at life. You can be angry or you can appreciate what you have been given,” she said.

    “Chase was meant to be with us.”