Often abbreviated simply as SCA, Spinocerebellar ataxia is defined as a degenerative genetic disease which can take on multiple forms . Therefore, other names for this condition include Spinocerebellar degeneration or Spinocerebellar atrophy. As the name may already hint, this disorder affects the central nervous system and as of yet, there is no known cure. It can therefore often be fatal over time. Treatments have likewise proven themselves to be ineffective and this ailment is able to occur at any age; regardless of previous conditions or an existing comorbidity with other ailments. While age is not considered to be an active variable, scientists believe that there is a genetic component in regards to both its onset and prognosis. This is compounded by the fact that many carriers were unaware that they had a genetic predisposition until their offspring begin to show symptoms . According to recent studies, approximately 150,000 individuals within the United State shave been diagnosed with Spinocerebellar ataxia .
Spinocerebellar Ataxia In Relation to Other Degenerative Neurological Disorders
Before delving into the specifics in terms of Spinocerebellar ataxia, it is important to point out some clinical and diagnostic differences between this condition and similar disorders. One of the defining factors (mentioned in more detail later) is that SCA mainly exhibits physical symptoms as opposed to mental incapacitation . The sufferer will rarely exhibit conditions such as memory impairment, mental processing problems or speech issues (those derived from the portions of the brain that controls linguistics such as Broca’s area). This is in direct relation to Parkinsonian patients and those who are diagnosed with Alzheimer’s disease. In either of these cases, there is a notable degradation of mental capacity that will often degrade over time.
This tends to be one of the most frustrating aspects in relation to Spinocerebellar ataxia. The brain and its associated thought processes remain fully intact. In most cases, the patient is fully aware of his or her condition. As SCA progresses, this can cause a great deal of emotional stress and consternation. We should still note here that many of the psychological treatments are similar to those associated with other diseases of the brain and spinal column. The aim is generally to alleviate emotional issues and to provide the patient with an ability to look at his or her situation from a different perspective.
Spinocerebellar ataxia is not known to be cured by any current medications . While drugs are able to provide relief in terms of its symptoms, they will offer little relief in terms of inhibiting the progression or the onset of the disease. It should be noted here that are are still certain drugs which have been shown to boast mild relief from a short-term perspective. As should be expected, the majority of these medications will work on the chemical level as opposed to addressing the underlying genetic components of Spinocerebellar ataxia. There can also be times when medications provide little relief from one’s symptoms (particularly if the disease has progressed to an advanced stage).
Furthermore, Spinocerebellar ataxia is much less understood when compared to other conditions. We will strive to examine this situation in more detail later in the article. This is quite significant, for research and treatment options are progressing. While it is known that SCA is a genetic disorder, the causes and (possibly) environmental factors are yet to be completely understood. The interactions between different genes and autosomes is only just being clarified on a clinical level. Ongoing trials may very well provide the information necessary to crack this rather daunting code. This signifies that a breakthrough may be just around the corner or that one could be decades away.
Confounding Factors and Classification
One of the issues regarding the rather difficult nature of possible treatments revolves around the fact that currently, more than 60 different variants of SCA are known to exist. Amongst these is a condition known as Freidreich’s ataxia (further below). All of thee genetic variants have only been identified in post-mortem procedures; there is currently no known blood or genetic examinations that can determine which type a living individual has. It is also likely that additional subtypes of SCA remain hidden and scientists surmise that an additional number will be discovered in the future. The most common diagnoses are the result of an MRI examination of degenerated neurological tissue, a spinal tap, an analysis of any manifestation of physical symptoms or an in-depth family genetic history (and possibly mitigating factors involving predisposition). It is hoped that as science progresses into the future, technicians will be able to develop proactive diagnostic techniques which can be employed for early detection and possible options for treatment methods that do not yet exist.
Another factor which has served to muddle the understanding of SCA is that it is frequently misdiagnosed. In other words, it can be mistaken for other conditions. This is a particular concern if there is a comorbidity between SCA and other illnesses (such as Broca’s aphasia or Alzheimer’s disease). Thus, we can assume that the initial figure mentioned in regards to the purported 150,000 cases in the United States may very well be under-reported.
Finally, Spinocerebellar ataxia has not been studied on a long-term basis as other diseases have. There is little longitudinal data in terms of incidence rates, survivability and demographics. It is therefore erroneous to believe that the current information available reflects that which will be provided in the near future. As the years progress, it will be quite interesting to observe what data is obtained and how this information can be applied within the clinician-patient scenario.
Spinocerebellar ataxia is found within a category of conditions that is known as polyglutamine diseases . In turn, these can be classified under the larger segment of trinucleotide repeat disorders. In general terms, these diseases are thought to be a result of DNA triplets which have undergone abnormal or unstable rates of expansion. It is interesting to note that within one subcategory of these ailments can be found both Huntington’s disease (otherwise known simply as HD) and the aforementioned Spinocerebellar ataxia can be found within one subcategory of this ailment. It may be surmised that there is an interconnected relationship between both although as of yet, no definitive results have been established.
Another feature that all polyglutamine diseases share in common is that they are known to exhibit genetic anticipation. In other words, SCA and others within this group are said to have more of a proclivity to occur with future generations. As these disorders are the direct result of the duplication of one codon, it only stands to reason that such a generational proclivity exists. The end result of such inheritance can be an earlier onset of SCA as well as more severe symptoms and a decreased life expectancy.
However, this may actually be a slight blessing in disguise. Should more exacting identification procedures come to light, it could be possible (over time) to eliminate Spinocerebellar ataxia from one generation to the next. This would make the offspring of future generations completely safe from developing the illness.
We should note here that polyglutamine diseases (PolyQ diseases) and the respective subtype of SCA can be broken down into numerous categories including:
Additionally, there are certain types of Spinocerebellar ataxia which are considered to be non-polyglutamine in their nature (not requiring the amino acid glutamine to be present). These are:
- Freidreich’s ataxia
- Myonic dystrophy (commonly known as DM)
In all of these cases, the numerical nomenclature has little to to with any genetic or amino acid considerations. The numbers following SCA correspond to the order in which the specific subtype was found by scientists (hence SCA1, SCA2, SCA3 and so forth). SCA1 was first isolated and identified in 1993 and as of the present, no less than 29 different mutagenic causes have been identified by professionals.
As observed previously, the treatment of SCA has been hindered by the fact that age does not necessarily seem to be a predominant factor. The differing subtypes exhibit equally disparate onset times; some as low as 1.5 years of age. It should therefore be no surprise that the associated symptoms can very widely. These will be discussed in a later section.
This type of ataxia is grouped within the larger category of ataxias, but it is important to mention that there are some notable differences . As opposed to SCA, there is little effect upon the cognitive functions of the patient. This is in direct contrast to many other forms of SCA and thus, this condition has been termed a bit differently. It will generally progress until a wheelchair or another type of assisted mobility device is required.
One reason for this disparity results from the fact that the degeneration takes place in the spinal cord as opposed to within the brain tissue itself. Therefore, there is more motor impairment than there are cognitive issues. It also affects sensory neurons located in the cerebellum in comparison to the “thinking” areas of the brain. Much like other ataxias, the myelin sheath becomes thinner over time. This impairs and dilutes the signals between the synapses and the uptake of essential neurotransmitters is dramatically reduced. The end result is an eventual degradation of motor control and similar functions .
Some of the symptoms which are unique to Freideriech’s ataxia include:
- Muscular weakness which worsens over time.
- Impairment of coordination (specifically in terms of balance and left-right simultaneous tasks)
- Speech problems.
- A loss of hearing.
- Atrial fibrillations and other cardiac disorders.
- (In 20 per cent) the onset of diabetes with no other apparent causes .
The reason that Freidreich’s ataxia has been mentioned here is to highlight the differences between this condition and the symptoms associated with Spinocerebellar ataxia.
As a result of the pathology being comparatively easier to monitor (only in this case), there are certain treatment options such as rehabilitative therapy alongside drugs including Idebenone (an antioxidant) and RG2833 (a histone deacetylase inhibitor).
Symptoms of Spinocerebellar Ataxia
This is a rather complicated area to address considering the amount of subtypes of the disease which are currently known. However, some of the generalised observations include (but may not necessarily be limited to):
- A progressive inability to walk and maintain one’s balance.
- Speech issues (as above).
- Poor cognitive function (in some later stages).
- Tremors in the extremities such as the hands and the feet.
- Eye movement problems.
- An eventual degeneration of the cerebellum.
Many patients will still retain their full mental capacity while experiencing these conditions. This makes SCA particularly difficult to cope with from an emotional and a psychological point of view. Now that we have taken a look at the generalised symptoms, it is a good idea to examine some of the other prodromes which are present depending upon the type of SCA that one may have (even if this is determined after a post-mortem examination).
Some of the symptoms of this subtype include the involuntary movement of the eyes (known as hypermetric saccades) and upper motor neuron conditions. These can include limbic movements, difficulty maintaining one’s head position, trouble swallowing, jaw spasms, balance and arm position. This condition can last between 10 and 35 years although the most common length is 15 years. An abnormality in chromosome 6p has been shown to influence the development of SCA1 .
In this case, the involuntary movements of the eyes (saccades) are noticeably slower when compared to those associated with SCA1. Another condition known as areflexia may be present in conjunction This is associated with a pronounced lack of response to neurological stimuli (found through testing along with the use of an EEG). Those between 30 and 40 years may develop this variant. The average duration is 10 years while it can last for up to 30 years. Chromosome 12q is related to SCA2 .
Symptoms of SCA3 include a condition known as a nystagmus. This is defined as an oscillatory movement of the eyes that is normally caused by the gaze from another individual. This is involuntary and can be quite rapid in its nature; leading to balance issues and difficulty in regards to interpersonal interaction). Similar upper motor neuron conditions (such as mentioned above) may exist alongside these eye movements. SCA3 occurs during the fourth decade of one’s life and can last for up to 20 years. This subtype is also known as Machado-Joseph disease . The 14q chromosome is involved with the onset of SCA3.
The primary indicator of this condition can be seen in a diminished response (or an absence) of neurological reflexes. SCA4 has been known to affect individuals as young as 19 and as old as 72. The ailment can last for decades. Chromosome 16q has been shown to be responsible for SCA4.
One of the unique aspects of this condition is that it is manifested purely in the cerebellum. Therefore, the extremities are mainly affected although it is not yet understood if other symptoms may be present (such as diminished upper motor neuron response). SCA5 can occur between the third and fourth decade of life. There is a general life expectancy of less than 25 years. Chromosome 11 is responsible for SCA5.
SCA6 is notable in that it can occur in individuals that are 65 years old or later. Vertigo is one of the main symptoms although pronounced nystagmus may also be present. Although SCA6 is known to affect those later in life, some individuals as young as 19 years have developed the condition. It will normally last for a maximum of 25 years. A malfunctioning gene related to calcium channels is a cause of SCA6.
Slow eye movements combined with macular degeneration (loss of eyesight over time) are indicative of this subtype. As previously, upper motor neuron problems could also exist. This subtype normally begins to show itself during the third or fourth decade of one’s life. While the duration is normally 20 years, an early onset is generally correlated with a better overall prognosis.
SCA8 is not limited to a specific age range; it can occur during any time of one’s life. Motor issues such as a lack of coordination and instability are known to be present in this case. Nystagmus will often be present as well. SCA8 has been shown to be present in age groups ranging from 18 to 65 years.
This is one of the only subtypes that is associated with seizures. Thus, there is a hint that different regions of the brain (and therefore specific myelin sheaths) may be affected). There have been few studies in regards to this condition. The patient age was 36 years and the duration of the illness was 9 years. The chromosome 22q alongside an abnormality with a pentanucleotide repeat are thought to influence this subtype.
As with SCA8, SCA11 can occur at any time. However, this is one of the more mild forms of spinocerebellar ataxia. The patient normally maintains the bulk of his or her mobility and ambulatory care is rarely required. SCA11 can be manifested in anyone between 15 and 70 years old. The 15q DNA strand may be the cause of SCA11.
Head and hand tremors are normally present along with the generalised loss of motor functions. These movements may be mistaken for a Parkinsonian pathology on occasion. SCA12 occurs at an average age of 33 years while it has been diagnosed in children as young as 8 years and adults as old as 55 years . Problems with a strand known as 5q within the DNA chain are thought to cause this condition.
SCA13 can occur as early as childhood. This primarily depends upon the type of mutation present. With such an early onset, the normal functioning of the growing brain is severely impaired. This may result in mental retardation. However, there may very well be other degenerative conditions which will shorten one’s overall lifespan. An issue with the 19q DNA strand causes this subtype.
A sudden (and unprovoked) twitching of the eye muscles that is known as myoclonus defines this category. There are no rhythms or patterns in this case. This condition is also present in other neurological disorders. Thus, misdiagnoses are common. SCA 14 is known to be expressed between 12 and 42 years; the mean age being 28 years old. It can last for up to 3 decades. Like SCA13, abnormalities in the 19q DNA strand are thought to cause this condition .
Tremors in the head and the hand are common with one who is suspected to have SCA16. Cognitive functions remain present while balance and gait are rarely impacted. SCA (on average) can develop from 39 years old and onwards. It may last between 1 and 40 years. SCA16 is the result of a DNA strand known as 8q.
These 16 different subtypes represent only those conditions of ataxia which are understood and have been shown to exist in clinical cases. After reading through the symptoms associated with each one, it is easy to see why understanding which ataxia subtype is present from a clinical point of view can be challenging. Furthermore, it is important to come to a correct diagnosis in terms of SCA and its similarity to Freidereich’s ataxia.
Now that we have examined the most prevalent symptoms associated with Spinocerebellar ataxia, there are a few important points to note here. There are specific geographic origins associated with certain subtypes. For example, SCA2 has been found to originate in Cuba. SCA3 has been traced to Portugal (the Azores in particular). SCA10 originated in Mexico. These three examples only highlight the fact that such a disorder is so difficult to track and that genetics indeed play an important function .
Perhaps more importantly, the term “duration” here refers to the progression of the specific subtype before death. As we can see, different variants will obviously have equally different prognoses. One of the most prominent considerations is that unlike other neurologically degenerative disorders, SCA is not yet fully understood. Furthermore, the pool of subjects is decidedly limited due to both diagnostic and pathological issues. These ranges could therefore not be completely accurate. For example, one who has been shown to have developed SCA10 may very well live much longer than the predicted duration of a mere 9 years. As the studies are ongoing, it is hoped that a higher degree of accuracy (and a more representative mortality rate) will be possible.
There are also other mitigating issues such as the ability to tie certain genes to a specific subtype. Indeed, there may very well be other causal factors that have not yet be determined and additional genes could be present. There is the additional possibility that environmental or hormonal factors could play an important role. Thus, these summations represent what can only be called a somewhat limited knowledge base as of yet. The impacts of phenotypes as well as the inheritance of the disease allele are also not fully understood.
Underlying (and Surmised) Causes
As we have previously seen, it is known from a general standpoint that condition can be traced back to a genetic and chromosomal origin. Interestingly enough, Spinocerebellar ataxia is able to be inherited from both dominant and recessive autosomes. A third factor is what is known as x-linkage. This possibility should be looked at in further detail.
X-Linkage and the Role of Autosomes
The basic principle behind x-linkage is the fact that much more genetic information (and potentially mutations) are present on the female X chromosome . This is in direct contrast to the less-common and male-oriented Y chromosome. To put it simply, the female is represented by XX chromosome while the male is defined by an XY chromosome.
An intriguing fact in regards to x-linked conditions is that they often prefer to exhibit their traits in one gender over another. In the case of SCA, this is not the case. SCA displays itself equally in both men and women. This arises from the fact that the mutations are present in what are known as autosomes (chromosomes without a gender-specific quality). As we know, genes come in pairs. Dominant genes which contain Spinocerebellar ataxia will take precedence over recessive genes. Therefore, children with one parent who contains an x-linked dominant ataxia gene have a 50 per cent chance of developing the condition over the course of their lives.
Recessive Genetic Patterns
Note that this case is quite different when compared with parents with a dominant ataxia-oriented autosome. While males and females are likewise affected equally, it will take what is known as a “double dose” for the condition to be passed on to any offspring. To put it another way, it is necessary for both parents to carry this mutation in order to affect their child. The statistics can be broken down as follows:
- There is a 5 per cent chance of a child developing SCA if both parents are known to have a recessive SCA autosome
- There is a 50 per cent chance of inheriting one autosome from either parent (this results in the offspring becoming a carrier for future generations).
- There is a 25 per cent chance that no mutated autosomes are inherited whatsoever and thus, the condition can be eradicated from future generations (assuming that any future partners are free from the SCA autosome)
The problem here is that one who inherits a single ataxia gene will show no symptoms (the primary quality of a recessive trait). This gene can therefore be passed on for generations until it is exhibited by sheer statistics alone. This has made it quite difficult for scientists to track the exact origin of this ataxia as well as to diagnose the chances of inheritance. In many cases, such a longitudinal family history was simply not present.
It is not yet known if environmental factors play an active role in the development of Spinocerebellar ataxia. However, previous studies have conclusively shown that mental and physical stress can lead to an excess production of free radicals . These can affect neurological degeneration (particularly with those who may already be predisposed to develop SCA).
Otherwise known as oxidative stress (OS), these free radicals are prone to attack what would have otherwise been considered healthy nerve cells. An imbalanced metabolism can result in the premature development of aforementioned illnesses such as Parkinson’s disease and Alzheimer’s disease. It therefore stands to reason that these very same reactive substances could play a role in the activation of Spinocerebellar ataxia. Antioxidant therapy may be an option and as logic dictates, those who may be found to have a recessive SCA gene may very well be advised to eat foods rich in these substances in order to delay (or prevent) the illness from exhibiting physical symptoms. However, this viewpoint is extrapolated greatly in terms of its usefulness as well as its ultimate effectiveness. As we have seen previously, SCA is considered to be a gene-triggered condition. It is therefore unwise to draw any conclusions in regards to what (if any) roles antioxidants may play within its pathogenesis and treatment.
There have been no conclusive studies to clearly illlustrate that drugs (illicit) or alcohol play a role in SCA. Still, it can be extrapolated that these substances may worsen the symptoms. This is particularly the case with alcohol, for its consumption will temporarily change the chemistry within the brain. In turn, mild effects may become more severe when combined with dehydration, hangovers and other alcohol-induced conditions.
There has also been a slight amount of confusion in regards to the influence (or lack thereof) of aluminium in regards to Spinocerebellar ataxia. It needs to be pointed out here that as of yet, there has been no causal link between this metal and the activation of the disease. Many tend to “lump” such a synergy in together with other degenerative disorders such as Alzheimer’s disease. While this is not to say that the metal is completely unrelated, avoiding products or packages that contain aluminium has not shown to make an difference in terms of incidence rates.
We should finally note that stress has been known to activate many dormant conditions that may have otherwise gone unnoticed. So, it makes a good deal of sense to surmise that Spinocerebellar ataxia and its chances of occurring could be exacerbated by an increase of hormones associated with heightened levels of physiological stress (such as cortisol).
Diagnosis of SCA
As mentioned earlier, the primary means of diagnosis will revolve around one of two methods:
- A post-mortem examination.
- Ascertaining the specific symptoms and ruling out other degenerative diseases.
However, these are only partially effective and as there are no current options in terms of reversal, the efficacy of diagnosis is debatable. One interesting advancement is in the ability to prenatally diagnose some forms of Spinocerebellar ataxia (SCA3 or Machado-Joseph disease). This form is predominant in Taiwan and there are now preliminary tests which are able to determine risk factors involved with giving birth to a child that may exhibit the symptoms of SCA3. Although this test is only currently capable of making observations in regards to the SCA3 subtype, it is hoped that future innovations may enable doctors to detect other variants that may be present. Thus, the mother can be provided the choice of a pregnancy termination as well as other care options. This is able to lessen the emotional burden on parents while equipping caregivers with the tools required to alleviate any potential symptoms.
Management and Treatment Options
As we have seen earlier, there is currently no known cure for Spinocerebellar ataxia. This is a degenerative and progressive disease with a mortality rate that increases with time. However, we need to point out that not every subtype will result in death. Doctors are trying to design treatment options which tend to alleviate the associated symptoms as opposed to targeting the genetic issue itself. Their methods will depend upon the subtype as well as the ailments that the patient suffers from. Some of the main symptoms include :
- Sleep disorders.
- Involuntary tremors (the most common symptom of ataxia).
- Emotional issues such as depression, agoraphobia and GAD (generalised anxiety disorder).
We will look at the emotional impacts of Spinocerebellar ataxia in greater detail later in this subsection.
Ataxia and Pharmacological Options
There are several medications that are designed to treat Spinocerebellar ataxia and as highlighted previously, these are meant to mitigate its symptoms as opposed to ablate the genetic condition of ataxia itself. It is thought that with further research, there may be hope in terms of gene therapy or through an increased understanding of the ailment on a molecular level. Still, some of the main drug-related approaches relate to the specific symptom that is exhibited. Examples can be seen below.
Tremors may be minimised (but rarely eliminated) through the use of beta blockers such as Propranolol . Note that this chemical is also useful in the treatment of concurrent symptoms such as PTSD, anxiety and heart issues. Another option is an anti-epilepsy drug (assuming that the ataxia results in seizures) known as Topamax (topiramate). This can also be helpful in alleviating the symptoms of migraines.
As should be surmised, sleep disorders can be another secondary effect of SCA due to the decreased levels of comfort and notable levels of emotional stress. In this case, some physicians may choose to employ Benzodiazepines . Some of the most common include Klonopin (clonazepam), Valium (diazepam), Xanax (alprazolam) and Ativan (lorazepam). It is important to note here that Benzodiazepines can be contraindicated should other conditions be present that are being treated with medications (such as MAO inhibitors).
In the rare cases when the eyes themselves become affected (not including the spasmodic movements mentioned earlier), a class of medicines known as anti-angiogenic drugs could be employed . These are commonly employed to treat age-related macular degeneration although there may be some promise in terms of Spinocerebellar ataxia.
An interesting study highlights that certain specific drugs can produce viable (albeit short-term) results in some patients (the SCA2 subtype of ataxia). In one experiment carried out in 2004, five patients were given a dose of Zolpide (10 mg). Four out of the five showed an improvement within one hour of its ingestion. In one of the patients the incidences of tremors, ataxia and gait problems improved substantially . This drug has also been shown to ameliorate other conditions such as catatonia, aphasia and mutism. Brain injury cases have also been positively affected by the prescription of this drug. It is thought that an interaction with GABA (gamma-aminobutyric acid) plays an important role.
As before, it is important to recall that Zoldipem is only intended to treat the symptoms of Spinocerebellar ataxia. Furthermore, this medicine is classed as a nonbenzodiazapine. There is a slight risk of addiction over time and Zoldipem may negatively interact with other medications that are present. This was a short-term study. Due to its non-longitudinal basis, definitive effects in regards to other subtypes of SCA are not yet known.
The Stem Cell Possibility
One interesting observation that has emerged involves the use of stem cells as an attempt to directly counteract the physical nature of Spinocerebellar ataxia. As portions of the brain and the spine are normally affected, some scientists have surmised that treatment with these unspecified cells may produce results that are more permanent and beneficial when compared to palliative methods .
It is first important to appreciate how stem cells function. These cells are essentially what may be called “blank slates” in terms of their role within the body. Through processes that are not yet fully understood, they will differentiate into cells which are intended to work within certain areas of the body. Examples can include connective tissue, bone, muscle and neurons. The reason that stem cells show so much promise is that they are readily accepted by the recipient and they can adapt into other forms. These new cells will thereafter serve as a “replacement” to damaged or defective tissue. In terms of SCA treatment, it is hoped that such stem cells can be inserted and provide the neurological transmissions that would otherwise be lacking. Thus, symptoms can be improved and some surmise that the condition itself may be reversed. It is still wise to note that stem cell research is in its early faces. Many technical and legal hurdles need to be overcome.
Recent research conducted at St Michael’s Hospital in Shanghai, China may represent a breakthrough in how future medical practitioners approach Spinocerebellar ataxia. One study proposes injecting stem cells directly into the spinal cord via lumbar puncture. Initial observations have hinted that incidences of tremors are reduced and and some of the ocular problems are alleviated. Regardless of the promise that stem cells may have, it needs to be mentioned that this type of research is still in its infancy. Furthermore, it is unclear as to whether or not stem cell transplantation will extend the longevity of ataxia patients or merely improve their quality of life.
Emotional and Psychological Support for Spinocerebellar Ataxia Sufferers
One of the main issues of most forms of Spinocerebellar ataxia is the fact that (generally) all cognitive functions remain intact. This can be particularly distressing for the patient, as he or she is likely aware of their condition. Such a situation can often result in instances of severe depression and other emotional issues. Thus, doctors will frequently attempt to treat the sufferer as well as his her her mental needs by referring them to a trained specialist. In fact, this emotional toll can be likened to those who suffer from Parkinson’s disease and similar degenerative conditions . The primary difference is that as the age of onset in regards to SCA varies, younger patients may have a particularly difficult time accepting their situation.
Clinical therapy therefore plays an extremely important role in terms of providing a positive outlook for ataxia patients. This is also critical to maintain the mobility of the sufferer. As has been seen in many other conditions, the emotional state of an individual can have a very real impact upon his or her prognosis over time. There may be instances when medications such as tricyclic antidepressants or MAO inhibitors could be prescribed. This will depend upon the condition of the individual as well as the presence of any other medication that may be currently prescribed.
Another useful outlet can be see in the number of SCA support groups available online. This enables sufferers to connect with like-minded individuals and follow up on much of the latest research. Such forums can be powerful tools in terms of decreasing the feelings of isolation while simultaneously providing individuals with the chance to appreciate others who are in similar positions. Chat rooms and social media pages related to Spinocerebellar ataxia are likewise available.
Maintaining one’s level of physical independence is important for a number of reasons. First, such mobility will help to increase feelings of health and avoid other emotional issues. Secondly, those who lack mobility are much more likely to suffer from other conditions such as poor circulation, heart issues, decreased muscle tone, diabetes and infections. The primary components of any rehabilitative programme will centre around gait training (walking practice) and postural balance (how to stand up straight and maintain this position). As should be expected, the success of these approaches will vary . This will depend upon the SCA subtype present, the progress of the condition, the age and the sheer emotional will of the patient. It has still been shown that those who suffer from SCA2 showed significant improvement in terms of balance after six months of dedicated physical therapy.
Another issue in terms of rehabilitation involves around muscular atrophy in patients who are older or who have been immobile for an extended period of time. In this case, muscle wasting is another concern. Therapists will therefore attempt to restore significant amounts of mobility through exercises involving range of motion as well as basic strength training techniques . Full-body movements such as lightweight squats, assisted lunges and swimming may help to improve coordination and balance over time.
Adaptive devices could be required and as before, this will depend upon the progress of the condition, the SCA subtype and the specific needs of the patient. Some common accessories can include (but may not be limited to) walkers, canes and wheelchairs. Other select devices can help those who may suffer from tremors and have difficulty cleansing or feeding themselves.
One randomised trial illustrated that those who underwent rehabilitative therapy showed significant improvement in terms of daily activities, balance, gait and even ataxia in general. Still, these gains were normally only maintained if the individual continued his or her treatment. Should they cease therapy, many of the benefits will be lost (although it should be noted that after 24 weeks, some evidence of improvement remained). Speech and language specialists may also be used for those who suffer from mandibular or tongue-related issues as a result of ataxia.
Palliative Care and Hospice
As with many degenerative neurological disorders, there will inevitably be times when Spinocerebellar ataxia reaches a stage where the intention of treatment revolves more around making the patient as comfortable as possible as opposed to finding other clinical options. As should be expected, this care will intend to alleviate any potential pain alongside the physical and emotional stresses associated with SCA.
There are several stipulations which indicate that palliative care may be necessary. Please keep in mind that these were developed through the American Society of Clinical Oncology and thus, the criteria may very well be slightly different in terms of SCA . The four tenets are:
- The patient is not able to adequately care for their basic needs.
- The has been no viable benefit from previous treatments.
- The individual is not able to participate in any further clinical trials.
- A medical professional believes that additional treatment options would serve little purpose.
An individual does not necessarily have to exhibit all of these conditions in order to be considered for palliative care. It should also be mentioned that such stipulations can differ from country to country (and region to region). Furthermore, this approach is quite different to hospice care.
Anyone who has reached a stage of SCA that has progressed to the point that no curative measures are possible will be considered for a hospice programme. This normally the final stage of care, for there is no hope for a recovery nor are any additional options available. As would be imagined, hospice involves making the patient as comfortable as possible. This approach can only be administered if two different physicians agree that the sufferer has less than six months to live under normal conditions. This does not necessarily signify that the individual may not live for much longer. It merely denotes that under current circumstances, there is little hope for any type of recovery. As there have been no documented cases (as of yet) of a patient recovering from Spinocerebellar ataxia, hospice may be the last option for those who develop a terminal subtype.
Tissue Donation Programmes
One of the most promising fields involves the donation of specific tissues to help further understand the pathology and impact of Spinocerebellar ataxia . This is a rather limited opportunity and currently, it is available only within the United States. This project is hosted by the National Ataxia Foundation. In most cases, the cellular materials that are required are from the brain and the spinal column. Thus, most SCA donations occur post-mortem. There is also a significant amount of planning involved to make certain that the harvested tissues have not suffered a significant amount of degradation. To put it simply, any cells must be extracted soon after one’s death. There are also procedures involved which can ensure that this process takes place soon after death. It is currently open to all age ranges and genders. It is hoped that researchers will be able to utilise these tissues to be able to further understand the impact of SCA from a cellular basis. Further information can be found at email@example.com.
As Spinocerebellar ataxia has gained a considerable amount of attention in recent times, here are a number of ongoing clinical trials available. Please keep in mind that the trials listed were valid when this article was written. There may be more or less depending upon availability. It is therefore wise to perform a generalised Internet search with terms such as “Spinocerebellar ataxia clinical trials” to encounter any new options. There are a handful of resources which may prove to be quite useful. Some of the websites include:
Registering for studies will normally require a physical examination as well as an active diagnosis of the condition. If possible, a specific subtype of SCA may open up further ataxia research opportunities.
As should be expected, there is a plethora of research that promises hope for those who suffer from Spinocerebellar ataxia. For the sake of brevity, we will only mention the studies which have been initiated during the past two years. Further information can be obtained by referring to the associated references seen at the conclusion of this article.
Wilfried Rossel, Ph.D.
The specific subtype of Spinocerebellar ataxia known as SCA36 has mainly been found in Japan and Spain. Many patients of this ataxia variant exhibit symptoms that are concurrent with LGA (Lou Gehrig’s Disease). These include gait ataxia, eye movement issues and other motor symptoms.
The aim of this project is to create what are known as “induced pluripotent stem cells” . It is hoped that these cells will thereafter develop into specified cells which can replace those that are functioning poorly (such as may be present within the brain and spinal cord). Dr. Rossel aims to develop SCA36 cultures within a dish and observe their behaviour. He can then observe the mechanism of the ataxia as well as test potential therapeutic treatment options utilising the aforementioned stem cells.
James L. Manley Ph.D.
Dr. Manley is mainly concerned with alleviating the symptoms of SCA2 (otherwise classified as Oculomotor Apraxia 2). He is particularly interested with the early onset of this condition and the severity of its symptoms from a longitudinal perspective. One of the genes that is known to mutate with SCA2 is known as SETX (senataxin). The function of SETX within the brain is still not completely understood. He aims to better appreciate the relationship between SETX and the onset of SCA2. Dr. Manley has also found that SETX plays a cellular role known as autophagy. In simpler terms, autophagy is associated with clearing defective or unnecessary cellular components. He aims to understand how SETX works within average cells and what role it plays within the activation of SCA2 in otherwise healthy individuals . He believes that a more circumspect appreciation of this function will help to uncover further ataxia treatments which are much more targeted and effective.
Andreia Teixeira-Castro Ph.D.
This doctor is involved with the treatment of SCA3. This was previously referred to as Machado-Joseph disease (MJD). This condition is primarily the result of mutations within a specific protein known as ataxin-3. Symptoms include difficulty swallowing and uncontrollable eye movements. As with all other ataxia symdromes, there is no existing cure or treatment. Dr. Teixeira-Castro intends to understand why the protein ataxin-3 (which is present throughout the body) specifically causes the degeneration and death of brain cells.
Her team intends to utilise a model of the disease within a specific type of worm. She hopes to be able to study the effects of this toxin on the brain cells of the host . Perhaps more importantly, the ultimate intention is to find specific neurons that are resistant to the impact of ataxin-3. It is hoped that by comparing the taxonomy of different neurons (those impacted versus those that remain free of SCA3) researchers can develop more targeted ataxia therapies.
Jeremy D.Schmahmann Ph..D
His study is titled “The Nature and Impact of Sleep Dysfunction in Cerebellar Ataxias”. His ultimate goal is to better understand the impact that any ataxi causes upon normal sleep cycles. He also points out that as the normal circadian rhythms (sleep cycles) are so important to maintain homeostasis, improving the quality of sleep may very well have a positive impact upon the lives of those who are suffering from Spinocerebellar ataxia.
He will particularly observe sleep disturbances that have the greatest impacts upon the health of the patient such as breathing issues, tremors and sleep apnea (the cessation of breathing during a normal resting phase). He hopes to interpret how these conditions affect cognition and mood (specifically referring to clinical depression). From this research, it is hoped that better ways to treat sleep disorders as well as generalised ataxia will be developed over time .
Janghoo Lim Ph.D.
Dr. Lim has begun examining the pathology behind SCA1 (the first type of Spinocerebellar ataxia discovered). By taking a “top-down” approach, he surmises that the mechanisms behind other derivatives can be better understood . He has specifically found an abnormality within a chemical that is known as Wnt-Î²-catenin . Technicalities aside, he believes that the SCA1 mutant chromosome can activate this chemical and this signal can be passed on to other cells. As a result, a cascading effect may cause the bulk degeneration of other proteins which are meant to shield the myolin sheaths between neurons. Thus, ataxia is the final result.
He intends to study the effects that a modification of this chemical has upon mice and combine these observations with other biological and molecular tests. It is thought that a more robust understanding of the pathogenesis of SCA1 can help to develop turnkey treatment solutions which are targeted around the specific subtype of SCA.
Susan Perlman Ph.D.
As opposed to the other researchers that we have seen so far. Dr. Perlman is involved with the collation and interpretation of empirical data . This intended to assist an organisation known as the Ataxia Clinical Research Consortium. Clinical care and research and emphasised within her desires.
She has also imported existing coded data into the National Ataxia Database (United States). This is quite important with the study of SCA1, SCA2, SCA3 and SCA6. She is allowing this resource to be open to researchers. They can store data here as well as interpret other observations that have already been made. The sharing of such important information may very well lead to the development of more effective ataxia treatments and ultimately, potential cures.
Richard Wojcikiewicz Ph.D.
Dr. Wojcikiewicz specialises in a condition that is known as Autosomal Dominant Sensory Ataxia (ASDA). This is thought to be caused by a mutation in the protein called RNF170. Such a condition falls under the overall ataxia profile (gait problems, sensory issues, loss of sensation in the extremities).
The molecular biology of this type of ataxia is still unknown as are the underlying mechanisms behind the associated genetic mutations. Dr. Wojcikiewicz plans to utilise his laboratory to understand the properties of this phenomenon . In turn, he intends to develop more targeted strategies that can address the plight of Spinocerebellar ataxia as a whole.
Christiane S. Hampe Ph.D.
Dr. Hampe is concerned with the pathogenesis of Spinocerebellar ataxia from a generalised standpoint . Her paper entitled Glutamate Decarboxylase in Cerebellar Ataxia intends to examine the enzyme of the same name. For the sake of this synopsis we will refer to glutamate decarboxylase simply as GAD. She intends to assess the role of GAD in terms of common ataxias. In particular, she hopes to establish the causal relationship between GAD and the neurotransmitter GABA (gamma-Aminobutyric acid). Utilising mice that already exhibit ataxia symptoms, Dr. Hampe will inject GAD into their systems to see whether or not a change in the current condition is observed. She also hopes to be able to culture a form of GAD which will not pass along its mutagenic traits but still functions normally in terms of enzymatic pathways. Behavioural tests will be performed to evaluate the efficacy of this treatment method. Should this method prove to alleviate ataxia-related symptoms, she hopes that it can be extrapolated to aid in the treatment of humans with this SCA.
William G Fairbrother, Ph.D
Dr. Fairbrother is interested in determine which genetic roots play a causal role in the development and prognosis of the entire category of SCA illnesses . One of the most interesting results that his lab discovered was that in more than 30 per cent of all cases, a protein may be destined for a mutation before the generation process of this protein has even begun. This is in direct contrast to other scientists who have mainly focused on ataxia mutations after they have already occurred.
His unique Spinocerebellar ataxia research intends to predict the causal factors in relation to SCA as opposed to finding treatment options. He has also developed a unique software package that is used in conjunction with these findings. This programming helps within genetic sequencing specifically in relation to ataxia.
Henry H. Houlden, Ph.D.
Dr. Houlden and his team are studying Spinocerebellar ataxia type 3 (SCA3). He observes that while the genetic defect which causes this form of ataxia is already known, it is still unclear when the illness will begin or how extensive it will be in terms of duration and severity . Thus, he concludes that there must be other factors involved which are not yet known. The aim of his study is to observe the numerous chemical reactions occurring in the brains of patients with Spinocerebellar ataxia. These will then be compared with the same reactions within the brains of normal patients.
He intends to compare the disparate results and see if there are any notable differences within the two categories. Not only does Dr. Houlden surmise that this could help those with the specific SCA3 ataxia, but there may very well be other forms of Spinocerebellar ataxia that may benefit from such a body of research.
Elide Mantuano, Doctor of Biology
Dr. Mantuano is interested in a series of ataxias known as Episodal ataxias . These are characterised by clinical symptoms such as migraines and vertigo while it is known that they are caused by genetic components. In particular, he is searching for the individual EA phenotype. In short, he aims to identify any new genes and their role within this form of ataxia.
The end results of this study could be the ability to increase the efficacy of molecularly diagnosing patients with this rare form of ataxia. In addition, the overall molecular mechanisms of this disease could be understood better. As with many of the other experiments, this can lead to better diagnoses and treatments options over time.
Gary Rance, Ph.D
Dr. Rance is concerned with the increasing role that the cerebellum appears to play in the host of Spinocerebellar ataxias . This area has recently been found to have an important impact upon the timing and coordination of both cognitive thought and language. This is important when we consider that specific subtypes of ataxias (SCA type 1) as well as Freidereich’s ataxia are known to sometimes impact cognitive abilities (particularly in later stages).
His study hopes to find a correlation between SCA1 and hearing impairment. It also will use imaging technology to uncover whether or not there are cerebellar structural changes to a control group and those with active SCA. He surmises that such abnormalities may be associated with hearing changes as well as a lack of fine motor control. The end result is hoped to be an increased understanding of how to perform more targeted levels of intervention. Finally, there may very well be a more in-depth appreciation of the entire classification of SCA as a whole.
Jason Christie, Ph.D.
This young researcher has been focusing upon Episodic ataxia Type-1 (EA1). He is basing his research around the observation that potassium channels within the cerebellum are adversely affected with the onset of SCA . As a result, he hopes to establish a definitive causal link between these channels and the severity of Episodic ataxia. There is also a possibility that a further comprehension of this relationship will open up new doors in terms of treating SCA entirely.
Alexander Urban, Ph.D.
Dr. Alexander is interested in the development and pathology of autosomal dominiant cerebellar ataxia (ADCA) in its relation to deafness and narcolepsy . He points out that the genetic component of this illness is already known. It is a result of a mutation in the DMNT1 gene. This is actually an important gene that plays a number of critical roles within the body. His aim is to understand exactly how this component is affected by the mutation and how its function within individual nerve cells differs from genes that have not been affected by any mutation.
He proposes quite a unique approach in order to study this phenomenon. First, Dr. Alexander will harvest and create stem cells from the skin of patients. These cells will then be caused to develop into neurons. He will then be able to study the actions of the mutated DMNT1 gene within these cells.
It should be mentioned that DMNT1 is known to impact the very structure of DNA. Dr. Alexander further proposes that he will be able to study how such DNA changes may have an effect upon other genes. Finally, he hopes to determine whether or not the DNA strands become unstable as a direct result of the mutation.
Jian Li, Ph.D.
Dr. Li is involved with the study of multiple types of Spinocerebellar ataxia . Dr. Jian points out that certain stress responses within cells may serve to suppress ataxia-related conditions. Some examples can be a sudden onset of heat, metabolic stress and oxidative stress. He hopes to better understand how these reactions are initiated by the neurons as well as how they communicate within one another to achieve a systemic level of protection. It is hoped that by the potential exploitation, the effects of SCA can be lowered (as they may suppress ataxia proteins which are seen as the partial cause of SCA).
Do-Hyung Kim Ph.D.
Dr. Kim is interested in the immunological pathways that may cause SCA1 to activate within certain individuals . One particular type of cell is known as a immunoproteasome. These are normally activated when stress or infection occurs, but he believes that their anti-inflammatory response may have an impact in other physiological roles that are not yet completely understood (and lead to ataxia). He also surmises that this cell could possibly negate the effect of aberrant proteins within the body. This would normally cause immunoproteasome to inhibit mechanisms that cause SCA1 to develop.
He proposes that this action may be negated if there is a large presence of mutated proteins (such as those which are involved with the proliferation of SCA1). To put it a bit simpler, Dr. Kim proposes that the process of immunosurveillance could have an impact upon neurological function and in turn, it may play an active role in the development of SCA1 (as well as many of the derivatives of Spinocerebellar ataxia).
Future Research and Possibilities
There is no doubt that Spinocerebellar ataxia is a daunting illness. This is indeed the case with many genetic disorders; particularly those with numerous subtypes and those which cannot be easily diagnosed with current technologies.
It is thought that future methods will help to increase the effectiveness of SCA treatments and even be able to reverse the condition on a genetic basis. This is naturally quite a challenging proposition, as genetic research and molecular biology are still at their infant stages when compared to traditional fields such as pharmacology and physical therapy.
Promise may also be found in the potential to detect parents who carry a recessive or dominant ataxia autosome. Should this condition be identified, risk factors could be more easily known and therefore, procedures such as sperm donation may be able to eradicate Spinocerebellar ataxia from the genetic “pool” over time. There would be an understandable amount of opposition from those who wish to have their own children and as seen earlier, some could take the risk in terms of the 25 per cent chance that an infant will be born with SCA.
As mentioned previously, advancements in stem cell research could indeed bring about an entirely new category of ataxia treatment options. It will be interesting to see what the future may hold in terms of this alternative.
This has been an in-depth description of Spinocerebellar ataxia. Although it is surmised that SCA has likely existed throughout human existence, it was not until recently that its various mechanisms have become more understood. Many believe that further SCA subtypes will emerge as diagnostic procedures continue to advance. Enhanced brain scanning including fMRI (functional magnetic resonance imaging) and PET (positron emission tomography) promise additional hope. As these procedures are able to show the processes of the brain and nervous system in a real-time scenario, there is always the possibility that the mechanisms of SCA will be further clarified. Thus, more targeted ataxia treatment options could become available.
In terms of pharmacological options to combat SCA, the primary confounding factor is that Spinocerebellar ataxia is rooted within genetics. Although gene therapy could eventually provide treatment options, current medicines are only able to alleviate the primary symptoms as opposed to cure the condition entirely. As we have pointed out earlier in this article, another issue is that Spinocerebellar ataxia may be treated with other medicines. As with any pharmacological intervention, there is always a danger that two different chemicals will adversely react with one another. Therefore, doctors can be hesitant to prescribe numerous drugs.
Therefore, most modern options tend to revolve around the proactive therapies that we have mentioned above. These include attempting to limit the impact of SCA on one’s life and providing therapeutic care for those who are no longer able to independently function. Like many other diseases which were once thought to be incurable, there remains a wide window in terms of ataxia research and development. Should science continue to advance at such a breakneck pace, there could very well prove to be a breakthrough cure for all variants in the not-so-distant future.
Those who are interested in learning more should make it a point to consult with the numerous authoritative website available across the Internet. Anyone who suspects that they may have the disease is strongly advised to seek the opinion of a health care professional. The scientific community will continue to work hard towards a further understanding of Spinocerebellar ataxia and hopefully, an eventual cure.
- Rossi, M; Perez-Lloret, S; Doldan, L; Cerquetti, D; Balej, J; Millar Vernetti, P; Hawkes, H; Cammarota, A; Merello, M (2014). “Autosomal dominant cerebellar ataxias: A systematic review of clinical features”. European Journal of Neurology 21 : 607–15.
- Pandolfo M (2009). “Friedreich ataxia: The clinical picture”. Journal of Neurology, 256: (1 Suppl), 3-8
- Thoren, Claes (June 1962). “Diabetes Mellitus in Friedreich’s Ataxia”. Acta Paediatrica 51: 239–247
- sca1 at NIH/UW GeneTests
- sca2 at NIH/UW GeneTests