December 18

No cerebellum? No problem!

What happens when you are born missing 80% of your neurons? Well, pretty much nothing, as it turns out, at least when it comes to those missing a cerebellum. Comprising 70 billion of the brain’s 85 billion neurons (Herculano-Houzel 2009), this hindbrain structure is “the primary center of motor coordination in the central nervous system” (except voluntary movement, which is mostly the domain of motor cortex), as well as aspects of cognition, timing, and balance (Chizhikov and Millen 2003). However, an examination of the smattering of cases in which people are born without cerebella demonstrates how surprisingly little the cerebellum is needed, given its size.

A recent case in China highlights this rather dramatically: here, a 24 year old woman checked into a hospital complaining of dizziness and nausea, and was promptly diagnosed with cerebellar agenesis, the fancy term for having a hole where your cerebellum should be (see figure, Yu et al 2014). Amazingly, she did not seem to exhibit any cognitive deficits, though she could not run or jump and she had not learned to walk until age 7. Up until that point, she had lived a more or less normal life, married with kids, despite missing approximately 70 billion of the brain’s 85 billion neurons, and would never have even realized that she had cerebrospinal fluid instead of a cerebellum had she not had a month-long bout of nausea.

no cerebellum!?

Multiple images of the brain of the Chinese patient recently found to be missing her cerebellum (from Yu et al 2014)

Further digging turns up more cases (of which there are perhaps two dozen or so reported) reveal a wide range of severities, though most seemed to have mild retardation and low IQ, with mild to severe movement and speech problems (Yu et al 2014). One of the nine total recorded living cases seemed to exhibit no symptoms whatsoever, and the medical records of another case, after cerebellar agenesis was discovered through a chance autopsy, again showed no defects with the poor cerebellum-less person managing to have a family and a steady job (Boyd 2010).  In another case, a 38 year-old man seemed mostly normal, with mild retardation and reasonably unimpeded movement and speech until an autopsy revealed cerebellar agenesis. The authors of a case study on the matter noted that he was clumsy, and his speech “occasionally was incomprehensible” (much like the author of this very piece), which seems par for the course in the handful of recorded cases. Like the others, he didn’t die due to complications from a missing cerebellum, instead electrocuting himself, which the authors dryly attribute to his having “enjoyed exploring and opening electrical appliances” (Leestma and Torres 2000). Another case attempts to link this cerebellar agenesis to suicidal tendency and depression, reviewing a suicidal subject whose autopsy revealed the utter lack of a cerebellum but, interestingly, no other deficits (see footnote for more information, Arcudi et al 2000).

To me, these cases where people show little to no effect of utterly lacking a cerebellum are quite astounding. Tellingly, one of the journal articles describing an undiagnosed-until-death adult case is titled “Unappreciated case of agenesis in the adult”, with “unappreciated” in this case being medical speak for ‘we were this guy’s doctors for years and had no idea that he was missing a large piece of his brain’. Overall, this has made me wonder how many people are missing chunks of their brain: in all of the less severe cases, only a chance autopsy or brain scan for unrelated matters showed a gaping hole where a cerebellum should be. In these cases, the brain is somehow able to make up for the absence of 80% of its neurons. Importantly, just because these people can seem unaffected without a cerebellum, doesn’t mean the cerebellum doesn’t do anything. Instead, it speaks to the amazing ability of the brain to adapt and change, its plasticity. As far as we know, these few relatively unaffected people developed without a cerebellum, allowing the brain to compensate for the lack of cerebellum, forming connections where they would otherwise not exist. Cross modal plasticity, where loss of a sense is compensated for by the strengthening of other senses [e.g. parts of visual cortex remap to become involved in sound location in a blind person, leading to heightened hearing ability (Collignon et al. 2009)], has been extensively characterized on a neuronal level. Of course, this is sort of the reverse situation, as all sensory input remains intact, but an important processing area is absent. Regardless, the ability to almost totally compensate for that much loss of neurons is remarkable and, on a mechanistic level, is rather baffling to science.

 

 footnote: While an isolated case (of the 10 I’ve reviewed), this may tie into the idea that the cerebellum is responsible for higher cognition and emotion at some level, a controversial point borne out by research showing differential cerebellar activity in happiness and disgust, among other evidence (Schienle and Scharmüller 2013)

 

Sources:

Arcudi G, Di Corato A, D’Agostino G, Marella GL. Cerebellar agenesis in a suicide. Am J Forensic Med Pathol. 2000 Mar;21(1):83-5.

Boyd CA. Cerebellar agenesis revisited. Brain. 2010 Mar;133(Pt 3):941-4. doi: 10.1093/brain/awp265.

Chizhikov V, Millen KJ. Development and malformations of the cerebellum in mice. Mol Genet Metab. 2003 Sep-Oct;80(1-2):54-65.

Collignon O, Davare M, Olivier E, De Volder AG. Reorganisation of the right occipito-parietal stream for auditory spatial processing in early blind humans. A transcranial magnetic stimulation study. Brain Topogr. 2009 May;21(3-4):232-40. doi: 10.1007/s10548-009-0075-8.

Herculano-Houzel S. The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci. 2009 Nov 9;3:31. doi: 10.3389/neuro.09.031.2009.

Leestma JE, Torres JV. Unappreciated agenesis of cerebellum in an adult: case report of a 38-year-old man. Am J Forensic Med Pathol. 2000 Jun;21(2):155-61.

Schienle A, Scharmüller W. Cerebellar activity and connectivity during the experience of disgust and happiness. Neuroscience. 2013 Aug 29;246:375-81. doi: 10.1016/j.neuroscience.2013.04.048. Epub 2013 Apr 30.

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. 2014 Aug 22. pii: awu239.

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