2011 Group Project 8

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Revision as of 00:00, 11 September 2011 by Z3332250 (talk | contribs) (→‎Treatment)
Note - This page is an undergraduate science embryology student group project 2011.
2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

Friedreich’s Ataxia

--Mark Hill 13:40, 8 September 2011 (EST) A well-structured project in terms of sub-headings. Student drag image included on project page. The problem, like all other projects, is a lack of section illustrations and figures. It currently just looks like a lot of writing, with each section slightly differently formatted.

  • Timeline - would look better vertical rather than horizontal.
  • Epidemiology - numbering should be either bullets or not at all. 1-3 and the separately Morbidity & Mortality?
  • Clinical Presentation - too many sub-sub headings, rationalise structure.
  • Postnatal Diagnosis - table formatting should be fixed.
  • Treatment - the text is poorly written/structured, go through this and organise to make sense.
  • Current Research - no text, a simple PubMed search would show you what is going on now.
  • Glossary - does not include all terms and acronyms used in the project.


Nikolaus Friedreich Portrait

Friedreich’s Ataxia (FRDA) is an extremely debilitating progressive neurodegenerative disease. FRDA, an autosomal recessive disorder, is the most common of the inherited ataxias and affects an estimated 1 in 50000 people. [1] [2] Patients suffering from FRDA have a normal presentation at birth and for a period of time thereafter. When the patient reaches the age of onset, which is approximately around the time of puberty the clinical phenotypes become noticable, such as ataxic gait. [3] Progressive weakness is also noticeable due to loss of skeletal muscle, which can cause pateints to become wheelchair bound with in 10-15 years of onset of the disease. [2] The disruption of the frataxin gene is often caused by a trinucleotide repetition of GAA, which is located on chromosome 9q13. [1] The result of this gene is a mitochondrial protein, frataxin, which is known to play a role in iron homeostasis. [4] This causes major disabilities in the tissues containing the fraxtain deficient mitochondria, such as skeletal and cardiac muscle, as well as, the central and peripheral nervous systems. [5] The results of FRDA involve an increase chance of developing diabetes mellitus and premature death due to congestive cardiac failure and cardiac arrhythmia. [4] [6] [7]


Nikolaus (Nicholas) Friedreich (1825-1882) was born into a family of physicians and studied medicine at the University of Würzburg, Germany. Pathology and neurology were his main interests in medicine and in 1858 he became the director of medicine at the Heidelberg medical clinic. [2] [8] During his years at Heidelberg he became intrigued with the clinical presentation of some of his patients who he described as having “degenerative atrophy of the posterior columns of the spinal cord that could affect several children of unaffected parents”. [2] In 1863, Friedreich wrote his first journal article on his findings about six of his patients who belonged to two separate families. These patients presented with similar clinical signs and with his continued research Friedreich collated the symptoms of ataxic gait, sensory loss, dysarthria, skeletal muscle weakness, foot irregularities, scoliosis and cardiac abnormalities linking there cause to a common factor. [4] [8] Friedreich proceeded to write several articles on the disease, which now bares his name Friedreich’s Ataxia.


1863 - Friedreich describes the clinical presentation of patients and publishes his findings. [8]

1882 -Brousse et al (1882) suggests that many diseases have been mistaken for FRDA, such as Charcot-Marie-Tooth disease or syphilis, which calls for further investigation and classification techniques. [4]

1907 -A study by Mott gave the first detailed description of the dentate nucleus and the role it plays in FRDA pathology. [3]

1988 -The chromosomal locus for Friedreich’s ataxia was mapped to chromosome 9q13. [6] [8]

1996 -Frataxin the mutated gene responsible for FRDA was discovered, which allowed for molecular testing and full clinical classification of the disease. [2] [6]


Distribution - FRDA is the most common form of inherited ataxic disease, affecting an estimated 1 in 50,000 people. [4] [1] [2]

Populations - It has been noted that Caucasian populations have a higher prevalence of FRDA with approximate carrier frequencies varying between 1:50 to 1:100. [3] Furthermore, Asian and African populations have a much lower prevalence of FDRA. [3] [4]

Gender - There has been no gender differentiation at this point in time, therefore, males and females have the same chance of inheriting FRDA. [3]

Age - Onset of FRDA is relatively early in life with symptoms normally appearing between 5-15 years of age, typically, patients are diagnosed before the age of 20. [9] [10] There are cases of late onset FRDA in which symptoms begin to show around 28 ± 13 years of age, remarkably these patients are less affect by cardiac dysfunction but are most likely to fall ill to neurological disability. [11] Furthermore, there has been known cases of very late onset FRDA but these cases are fairly uncommon and occur beyond the age of 40. [12]

Morbidity & Mortality FRDA is a progressive disease causing 95% patients to become wheelchair-bound by approximately 45 years of age. [10] Commonly, patients tend to lose the capability to walk nearing the age of 25. [10] Death of FRDA patients is principally triggered by cardiac dysfunction. In a study performed by Tsou et al, (2011) [9] 59% of patients died due to cardiac dysfunction, such as congestive heart failure and arrhythmia. 27.9% of patients died due to non-cardiac dysfunction, including pneumonia, sepsis and renal failure and the remaining patients died of unknown causes. [9] Death of FRDA patients remains quite young with the age of passing around 37.7 years of age ±14.4 years with patients suffering from cardiac dysfunction dying at an earlier age. [10] [9]


Genetic Component

GAA expansion or point mutation in first intron of frataxin gene

most individuals homozygous for repeat expansion, some heterozygous for repeat expansion & piont mutation


GAA repeat is unstable - leads to anticipating pattern of inheritance of GAA repeat

Genetic Expression


A model of pathogenesis in Friedreich's Ataxia

As FRDA is a ‘neurodegenerative disorder’ patients with FRDA are normal at birth until the ‘age of onset’ where symptoms present[13] due to (what is believed to be) iron build up in mitochondria. Studies on mouse models show that if the frataxin gene is totally knocked out, the embryo does not survive indicating that the frataxin gene is important for early development[14]. In humans, the GAA repeat on the frataxin gene causes a transcription defect on the gene impairing it's ability to produce frataxin (a mitochondrial protein).


In the past, the pathogenesis of cardiomyopathy in FRDA patients was relatively unknown[15], however it is now believed that the buildup of iron in mitochondria within cardiac muscle is part of the pathogenesis in cardiomyopathy of FRDA patients[16]. The iron build up results in what is described as ‘Fenton Chemistry’ where the excessive amounts of iron that are recruited into the mitochondria will produce a large quantity of HO˙. The production of HO˙ is of concern as it is a hydroxyl radical which is toxic to cells and it reacts to a variety of intracellular components including DNA[4]. The length of the GAA repeat expansion on the frataxin gene also has an impact on the pathogenesis of cardiomyopathy as it was discovered that ventricular hypertrophy is related to the length of the GAA repeat [17]. Patients with no signs of cardiomyopathy and late onset of symptoms has also been reported having shorter GAA repeats [18] [19].


FRDA produces a complex neuropathological phenotype within the central nervous system (CNS), as well as, the peripheral nervous system (PNS) and it is the neuropathology that differentiates this disease from other forms of hereditary ataxia. FRDA patients present with distinctive lesions of dorsal root ganglia (DRG), dorsal spinal roots, dorsal nuclei of Clarke, spinocerebellar and corticospinal tracts, cerebellum, dentate nuclei, and sensory nerves. [20] FRDA patients have consistent lesions in the DRG, which trigger secondary degeneration of the fibers in the spinocerebellar tracts and atrophy of the neurons in the dorsal nuclei of Clarke. Less consistent among FRDA patients are lesions occurring in the dentate nucleus, in addition to optic atrophy, and degeneration of the corticospinal tract.

The Dorsal Root Ganglia (DRG)

Cross Section of the Spinal Cord

The hallmark of FRDA involves atrophy of DRG and thinning of dorsal roots themselves within the PNS, refer to the figure of the Cross Section of the Spinal Cord. [21] The lesions of the large primary neurons in the DRG are an early clinical finding in the disease with neuropathological examinations of FRDA patients showing a decreased size of DRG along with grey staining of the thinned dorsal roots . [22] [2] Iron dysfunction, caused by mutation of the frataxin gene, highly affects the DRG causing a common characteristic of the disease, which includes demyelination and unsuitable regeneration of myelin of the dorsal root. [21] [23] The study by Mott et al, (1907) [2] highlighted the importance of the DRG, in which Friedreich himself did not seem to think played any role in this disease. It has been suggested that DRG pathology involves an age determined buildup of the GAA triplet repeat sequence “…thus, somatic instability of the expanded GAA triplet-repeat sequence may contribute directly to disease pathogenesis and progression.” [24] Furthermore, the experiment conducted by Lu et al, (2009) [23] measured the significance of frataxin depletion in Schwann cell and oligodendrocyte cell lines. Schwann cells are the supporting cells of the PNS and oligodendrocytes serve the same function in the CNS. Results showed that mainly Schwann cell succumbed to cell death and reduced proliferation. This highlights that the Schwann cells, which enwrap DRG are affected greatly by frataxin deficiency. [23] When abnormalities arise in Schwann cells, due to injury or genetics, they can cause demyelination, inappropriate proliferating and phagocytosis of debris. [25] The understanding of the pathological change within the peripheral nervous system is poorly understood, however, the damaged DRG seems be the basis of FRDA. [22] As the damage and/or loss of the neurons of DRG are seen to be the primary manifestations of FRDA many secondary affects stem from this area, such as;

  • The depletion of the centrally projecting axons of the DRG into the dorsal root. [2]
  • The loss of axons in the dorsal root explains the depletion of the dorsal column fibers and “…afferent connections to the dorsal nuclei of Clarke and the gray matter of the dorsal horns.” [2]

The Dorsal Nuclei of Clarke

The dorsal nuclei of Clarke are mainly found in the thoracic region of the spinal cord. These nuclei function to relay proprioceptive information from the lower extremities to the spinocerebellar tract. The information this nucleus receives arises from muscle spindles and Golgi tendon organs. Within the spinal cord the nuclei can be located in the intermediate grey matter, refer to the figure of the Cross Section of the Spinal Cord. It is within the grey matter that the dorsal nuclei of Clarke form synapses with the dorsal spinocerebellar tract, which will continue transmitting the sensory information in a rostral direction until it reaches the spinocerebellum. When FRDA abnormalities occur in this area it will assist in proprioceptive sensory loss, of mainly the lower extremities. This would contribute to clumsiness and unexplained falls before FRDA patients are wheel chair bound. [3]

The Spinocerebellar Tract

The Babinski Reflex

This spinal pathways is involved in passing sensory information from the spinal cord to the brain and/or cerebellum. The function of this tract is to carry proprioceptive information to the cerebellum, which allows the integration of sensory information with movement. The spinocerebellum is the only area of the cerebellum that receives peripheral sensory input. Specifically, this tract aids in ongoing control of voluntary movement, motor control, locomotion, posture and ongoing execution via its connection to the spinocerebellum. Notably, the lesions tend to occur in the dorsal spinocerebellar tract and are said to be secondary to DRG lesions. [2] Post mortem examination of patients suffering from FRDA are indicative of a small, atrophied spinal cord with degeneration in the dorsal columns, spinocerebellar and corticospinal tracts. [26] Pathogenesis of the spinocerebellar tract includes axonal degeneration, which is characterized by demyelination of the myelin sheath encapsulating the axon, which normally allows for rapid propagation of electrical impulses. Followed by degeneration of the underlying axon, which will in turn disrupt the function of the spinocerebellum itself causing symptoms, such as:

  • “…loss of spinocerebellar input to the cerebellar hemispheres due to transneuronal atrophy of the dorsal nuclei of Clarke.” [27]
  • Hypotonia- the loss of muscle tone, which is variable between the upper and lower extremities, with muscle tone being usually normal in the arms but the tone of the legs, can differ. [3]
  • Loss of position and vibration sense, which leads into dysmetria [2]
  • Ataxic gait
  • Intention tremor nearing target
  • Hyperreflexia in the lower extremities is common among patients, in which there is unrestricted flow of excitation to the motoneurons causing spastic movements
  • Decreased or abolished tendon reflexes along with sensory deprivation in corresponding dermatome, [2]
  • Diminished ability to perceive touch, light, temperature and pain, which is more prominent in the lower extremities
  • Babinski reflex (extensor plantar responses) and muscle weakness.

The Cerebellum

Lateral View of the Brain

The cerebellum (Latin for “little brain”) is a small structure that creates the hindbrain and is enclosed by the occipital bone, refer to the figure of the Lateral View of the Brain. The cerebellum contains more than 50% of the brains neurons but only takes up 10% of the human brains total volume. This densely packed structure is involved in:

  • Adjusting the outputs of the descending motor pathways, as it receives massive input from the motor cortex in the brain, as well as sensory receptors.
  • Regulatory functions in movement and posture, which allows the cerebellum to compare and evaluate motor/sensory discrepancies, which provide corrective responses.
  • Producing projections into the descending motor pathways.

The three functional nuclei of the cerebellum, namely the dentate, interposed and fastigial all play a central role in relaying information between the cortex and other brain structures, refer to the figure of the Transverse Section of the Cerebellum. [26] In FRDA the degeneration of cerebellum appears late in the course of the disease becoming apparent upon neurological examination when Purkinje fibre depletion can be seen and atrophy of the dentate nuclei is observable. [22]

The Dentate Nucleus

Transverse Section of the Cerebellum- Highlighting the three nuclei

Out of the three nuclei of the cerebellum the dentate nucleus undergoes considerable atrophy and has been said to be the most likely cause of the symptoms dysmetria, dysarthria, dysphagia. [27] The dentate nucleus has axonal “…projections into the motor, premotor, oculomotor, prefrontal and posterior parietal cortex,” [26] thus with degeneration at the dentate nucleus can cause secondary abnormalities at the aforementioned areas. Frataxin deficiency causes iron accumulation with in the mitochondria, which in turn cases oxidative damage. This may be responsible for the neuronal loss but further research is needed in this area before any definitive answers can be given. The cerebellum connects to the brainstem via the superior, middle and inferior peduncles. Upon post mortem dissection many FRDA patient’s display degeneration of the superior peduncles; this is where the efferent fibres of the dentate nucleus can be located. Interestingly, only large neuronal cells of this nucleus undergo atrophy, which highlights the selective nature of FRDA and the small neurons remain unaffected, however, further research needs to be complete before the reason for the selectivity is understood. [27]

The Corticospinal Tract

This descending pathway conveys information from the motor areas of the brain to the spinal cord. This spinal tracts is of great importance as it can direct or indirectly control the movement of muscles. The corticospinal tract is made up of two pathways:

  1. Lateral- which projects axon onto motoneurons and/or interneurons of distal muscles.
  2. Ventral- which projects axon onto motoneurons and/or interneurons of axial muscles.

It has been noted that in particular the distal portions of the corticospinal pathway fibers are severely affected, suggesting a dying-back degeneration. [22] Dying-back degeneration implies that degeneration occurs at the most proximal end of the axon and destructively works its way up toward the neuron. Within the cerebral cortex the corticospinal tract originates from pyramidal or Betz cells in which degeneration is apparent but to a reduced extent. [22] Results of lesion of the corticospinal tract can produce:

  • Muscle weakness, mainly of the lower extremities and is most prominent in extensors and abductors of the hip [28]
  • Positive Babinski reflex indicate involvement of the corticospinal tracts.

Clinical Presentation

Schematic drawing of scoliosis
Pes Cavus Foot Deformity


Friedreich's Ataxia (FRDA) often manifests before puberty to early adulthood. Progressive gait and limb ataxia, absent lower limb reflexes, extensor plantar responses (Babinski's sign), dysarthria, reduction in or loss of vibration sense and proprioception [29], [30] have over the years with some variations between authors, been considered primary symptoms vital for diagnosis of FRDA. Physical complaints such as chest pains [31] [32] indicative of cardiomyopathy scoliosis and foot deformity (pes cavus, hammer toe) are common and are required as secondary symptoms before FRDA is suspected[29].

See Diagnosis for more information on past diagnostic guidelines and current suggested diagnostic practice.


Complications of FRDA can have cardiac and pancreatic involvement as a secondary result of mitochondrial iron accumulation. Cardiac involvement is high (>90%)[33], and it is hypothesised that FRDA exacerbates existing cardiac risk factors and increases the chance of developing cardiomyopathy (eg: ventricular hypertrophy and tachycardia)[34]. Even in Friedreich's original description of his patients, 5 out of 6 patients had cardiac involvement[34]. Familial links in cardiomyopathy and familial groups affected with FRDA has been found to exist(P <0.01). Though it does not show as great a relationship of development to familial FRDA groups as diabetes [35].

Diabetes as a complication of FRDA is fairly straight forward with a clear reason as to why it occurs. In mouse models of FRDA, when the frataxin gene is disrupted the overall volume of beta-cells is reduced due to cell apoptosis, loss of beta-cell proliferation and increased Reactive Oxygen Speices (ROS)in islets[36]. It was found that the incidence of diabetes increases with sibling-ship relationships (P< 0.001)[35].


Previous papers have set guidelines for the diagnosis of FRDA and was first established by Geffory et al. (1976)[37] to include ataxia of limb and gait, absent reflexes in lower limbs, dysarthria, extensor plantar responses, muscle weakness and sensory loss on the back[35]. It was then revised by Harding (1981)[35] to exclude muscle weakness and sensory loss on the back, include the onset of FRDA before the end of puberty, ataxia of gait, dysarthria, loss of peripheral sense, and absent reflexes in the leg[35]. As these diagnostic criteria were set before genetic screening was available, the diagnostic criteria was often split into two categories of 'primary' and 'secondary' symptoms of which, primary symptoms were required for a diagnosis of FRDA and secondary symptoms acted as supporting evidence but diagnosis could not be made due to the possibility of other diseases which presented with those symptoms[29]. In a more recent review of FRDA diagnostic criteria, it is proposed that new three categories (not using the dated categories) of 'possible', 'probable' and 'definite' indicating the likelihood of FRDA should be used instead. Additionally, it was suggested to include lower limb areflexia and dysarthria, babinski's sign, or repolarisation abnormalities on the electrocardiogram (ie: abnormal T-wave) or repolarisation abnormalities in patients with retained lower limb reflexes to be able to make a possible diagnosis of FRDA[38]. Currently, patients who are suspected of having FRDA based on signs and symptoms (all adapted from previous FRDA diagnosis guidelines) are sent for genetic testing and are only diagnosed with FRDA after genetic testing confirms the diagnosis of FRDA.

Diagnostic Tools

The table below shows common diagnostic tools employed in the diagnosis of FRDA:

Diagnostic tool What it does How it diagnoses FRDA Image (if available)
Electromyogram (EMG) Measures the electrical activity of muscle cells by inserting needles into muscle fibers that is to be tested and asking the patient to tense the muscle[39]. EMG can detect denervation[39] such as present in motor neuron diseases or muscle denervation as present in FRDA. Electromyograph test (video): [1]
Electrocardiogram (ECG) Provides graphic presentation of the electrical activity or beat pattern of the heart If T wave inversion is present, it may be an indication myocardial hypertrophy[40] which is a hallmark of cardiac involvment in FRDA. T wave inversions are also common findings in patients with FRDA[32].
File:Schematic ECG.jpg
Schematic drawing of ECG waves
Normal ECG(video):[2]
Echocardiogram (ECHO) Records the position and motion of the heart muscle Identifies abnormalities in heart muscle such as hypertrophy of ventricles(useful for determining cardiac involvement)[41]. Normal Echocardiogram (video): [3]
Blood tests Checks for elevated glucose levels (in the event of diabetes developing) and vitamin E levels as individuals with FRDA often have low Vitamin E serum levels [42] Blood tests work to identify any possible complication of FRDA (ie: diabetes) and identifies patients who require vitamin E supplements to increase the body's antioxidant capabilities[42].
Blood test results for glucose and iron
Magnetic resonance imaging (MRI) Provide brain and spinal cord images that are useful for ruling out other neurological conditions and confirming dorsal root degeneration. Changes in the dorsal root or related neural structures involved in motor coordination can be monitored and identified with MRI. MRI has also been used to diagnose FRDA before the availability of genetic testing where the thinning of the cervical cord was an indication of neurodegeneration[13]. In a recent pilot study, the globus pallidus (involved in motor coordination) was found to improve with iron-chelation treatment using MRI technology[43]. Another paper found that MRI may be a useful tool in diagnosing FRDA and allows researchers to track neural atrophy[44]. MRI of heart (video): [4]
Computed tomography scans (CT scan) CT scans work similarly to the MRI in that it is used as an imaging tool to identify neurodegeneration. While CT scans can be used in a similar fashion to MRIs, it has been noted that CT scans only identified mild cerebellar atrophy in advanced patients perhaps due to low CT resolution in the neck[44]. CT scan of lung cancer (video): [5]
Nerve conduction studies (NCS) Measures the speed with which nerves transmit impulses by using two electrodes (one to send the impulse and the other to measure the response)[39]. Nerve conduction studies determines how far and if neurodegeneration has occurred by analysing amplitude, latency, duration, and conduction. Each item assessed will inform the clinician of the number of nerve fibers activated, integrity of myelin sheaths or axonal loss[39]. FRDA diagnosis may be considered if nerve conduction studies indicates nerve degeneration. Nerve conduction test (video): [6]
Genetic Testing
Prenatal Testing

Prenatal Diagnosis

Genetic Screening

Tight linkage to an adjacent DNA marker (MCT112) provides reliable tool for genetic screening [45]

Postnatal Diagnosis

Friedreich's Ataxia (FRDA) is often diagnosed based on presenting clinical symptoms but testing for the gene defect that causes it is taken as a definitive diagnosis. A paper on cardiac evaluation of Friedreich's Ataxia patients found that cardiac evaluation using any of the above cardiac testing techniques was a useful tool to compliment genetic testing in terms for screening for patients who should be tested for Friedreich's Ataxia[46]The table below summarises diagnostic steps prior to and after genetic testing was available.

Availability of genetic testing Diagnostic symptoms
Prior to genetic testing availability Only physical signs(eg: Scoliosis) and symptoms(eg: chest pains), age of onset and typical FRDA progression could identify it as FRDA. [30]
After genetic testing is available Physical complaints are used in conjunction with genetic testing to confirm FRDA. Due to genetic testing, [13]it has been discovered that FRDA can occur in individuals older than the typical diagnostic age (first two decades of life[47]).



As cardiomyopathy is believed to be caused by the production of toxic agents from the excess iron reacting within mitochondria, Iron-chelation had been studied for it's therapeutic action on removing excess iron in mouse models. Between treated mice and untreated mice, the treated mice showed a decrease in heart weight and heart to body ratio. This demonstrates that while chelation limits cardiomyopathy, it did not 'cure' the problem. As chelation did not lead to major iron depletion or toxicity reduction, and prevented iron accumulation in mice with the mutated frataxin gene it has opened up a possible treatment path of preventing mitochondrial iron build up - stopping the production of toxic agents and free radicals before they can be produced. Additionally, mice treated with chelation did not show any changes in the histology of the heart or any other major organ. It also did not lead to red blood cell loss, decreased hemoglobin concentration or hematocrit[48].


The most promising antioxidant treatments are Idebenone and Coenzyme Q10 with Vitamin E. Antioxidants have shown degree of reduction on oxidative stress in mitochondria, however there are ongoing trials to show its effectiveness[49].

  • Conenzyme Q10 is an electron carrier with a reduction of oxidative stress effect from the combination of vitamin E, combination of Q10 and vitamin E displayed a positive effect[50]. Where Q10 and vitamin E conveyed the cardiac and skeletal improvement with the betterment of the mitochondrial synthesis[51].
  • Idebnone operates with a duel function in which it reverses redox reactions that affects electron balance in the mitochondria while also supporting mitochondria functions to prevent damage[52]. Usage of Idebenone has been proven to reduce cardiac hypertrophy in FRDA indicating a 20% reduction on left ventricular mass from cardiac ultrasound in half the patients during trial[53], though the dosage of Idebenone give is at low dosage treatments of 5mg/kg/day which has shown reduction in cardiac hypertrophy[54]. Thus Idebenone is frequently used a treatment method although other alternatives are present including erythropoietin, histone deacetylase inhibitors and other gene-based strategies[55].

Current Research


  1. 1.0 1.1 1.2 <pubmed>11351269 </pubmed> Cite error: Invalid <ref> tag; name "PMID11351269" defined multiple times with different content
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 <pubmed>19283344</pubmed>
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 <pubmed>21315377</pubmed>
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 <pubmed>10633128</pubmed>
  5. <pubmed>12547248</pubmed>
  6. 6.0 6.1 6.2 <pubmed>10607838</pubmed>
  7. <pubmed>5673214</pubmed>
  8. 8.0 8.1 8.2 8.3 <pubmed>15090560</pubmed>
  9. 9.0 9.1 9.2 9.3 <pubmed>21652007</pubmed>
  10. 10.0 10.1 10.2 10.3 <pubmed>7272714</pubmed>
  11. <pubmed>21128039</pubmed>
  12. <pubmed>16092110</pubmed>
  13. 13.0 13.1 13.2 <pubmed>21315377</pubmed>
  14. <pubmed>10767347</pubmed>
  15. <pubmed>3593615</pubmed>
  16. <pubmed>18621680</pubmed>
  17. <pubmed>11269509</pubmed>
  18. <pubmed>9339708</pubmed>
  19. <pubmed>18759347</pubmed>
  20. <pubmed>19957189</pubmed>
  21. 21.0 21.1 <pubmed>19727777</pubmed>
  22. 22.0 22.1 22.2 22.3 22.4 <pubmed>12878293</pubmed>
  23. 23.0 23.1 23.2 <pubmed>19679182</pubmed>
  24. <pubmed>17262846</pubmed>
  25. <pubmed>21878126</pubmed>
  26. 26.0 26.1 26.2 <pubmed>21107777</pubmed>
  27. 27.0 27.1 27.2 <pubmed>21638087</pubmed>
  28. <pubmed>20301458</pubmed>
  29. 29.0 29.1 29.2 <pubmed>10633128</pubmed>
  30. 30.0 30.1 <pubmed>13872187</pubmed>
  31. <pubmed>7488466</pubmed>
  32. 32.0 32.1 <pubmed>3593615</pubmed>
  33. <pubmed>12045843</pubmed>
  34. 34.0 34.1 <pubmed>17622372</pubmed>
  35. 35.0 35.1 35.2 35.3 35.4 <pubmed>7272714</pubmed>
  36. <pubmed>12925693</pubmed>
  37. <pubmed>1087179</pubmed>
  38. <pubmed>11104216</pubmed>
  39. 39.0 39.1 39.2 39.3 <pubmed>21894276</pubmed>
  40. <pubmed>19486532</pubmed>
  41. <pubmed>2940284</pubmed>
  42. 42.0 42.1 <pubmed>11554913</pubmed>
  43. <pubmed>21791473</pubmed>
  44. 44.0 44.1 <pubmed>2759158</pubmed>
  45. <pubmed>2574535</pubmed>
  46. <pubmed>12045843</pubmed>
  47. <pubmed>19283344</pubmed>
  48. <pubmed>18621680</pubmed>
  49. 19283349</pubmed>
  50. <pubmed>19049556</pubmed>
  51. <pubmed>15824263</pubmed>
  52. <pubmed>19283347</pubmed>
  53. <pubmed>11907009</pubmed>
  54. <pubmed>19363628</pubmed>
  55. <pubmed>20856912</pubmed>

External Links

Video of Ataxic Gait [7]

Video of a Positive Babinski Sign - [8]

Video of Dysmetria - [9]

Video of Hyperreflexia - [10]

Video of nerve conduction test - [11]

Video of Electromyograph test - [12]

Video of a normal Echocardiogram - [13]

Video of an MRI (brain and heart)- Brain:[14] Heart:[15]

Video of CT scan (lung cancer) - [16]

Video of Electrocardiogram (normal) - [17]


Apoptosis - Programmed cell death.

Ataxic Gait - Involves a wide-based stance, lack of muscle coordination, errors in range and force of movement, delay in initiating movement.

Atrophy - Involves a decrease and/or wasting of an organ or tissue within the body.

Axon - The (usually long) process that transmits signals from the neuron it is connected to.

Cardiac Arrhythmia - Abnormal rate or beat of the heart, which can be either fast (tachycardia) or slow (bradycardia).

Chelation - chemicals that form soluble, complex molecules with certain metal ions, inactivating the ions so that they cannot normally react with other elements or ions... (ASTM)

CNS - Central Nervous System.

Demyelination - The loss of the myelin sheath surrounding an axon.

DRG -Dorsal Root Ganglion.

Dysarthria – A motor speech disorder causing slurring of words.

Dysmetria – Faulty judgment leads to the inability to perform basic movements, uncoordinated movement results.

Dysphagia – Involves difficultly of swallowing food, which can lead to coking of food or water, as well as, aspiration pneumonia.

Electrodes - A conductor which emits, controls, or collects the movement of electrons (ie: a current)

Erythropoietin - A hormone that stimulates red blood cell production.

FRDA - Friedreich's Ataxia.

GAA - Guanine Adenine Adenine Nucleotide Triplet.

Globus pallidus - A sub-cortical region of the brain, part of the extrapyramidal motor system.

Hematocrit - Measures the volume of red blood cells in blood.

Histone - A protein around which DNA coils to form chromatin.

Histone deacetylase inhibitors - These are compounds that interfere with enzymes that remove an acetyl group from histones.

Hyperreflexia – Over active reflexes responses, which can lead to spastic movements

Hypertrophy - Increasing in size of a organ or tissue.

Hypotonia - Decrease in muscle tone.

Myelin sheath - An insulating cover that wraps around individual nerves to increase the speed of conduction.

Neurological - Pertaining to the nervous system or nerves.

Pes cavus - Feet with abnormally high arches.

Pneumonia - Inflammatory condition of the lungs.

PNS - Peripheral Nervous System.

Positive Babinski Sign – The big toe extends up and backward whilst the other toes splay outward (abduct). This is sign of upper motoneuron disease.

Proprioception - Refers to the ability of sensing movement and position of muscles without visual guides. Required for hand-eye co-ordination.

Reactive Oxygen Speices (ROS) - It is a classification for chemically-reactive molecules containing oxygen.

Redox - a reversible chemical reaction in which one reaction is an oxidation and the reverse is a reduction

Scoliosis - Abnormal curving of the spine in the Coronal plane to form an 'S-shpe' when viewed from the front.

Sepsis - Infection of the blood, generally bacterial.

Tachycardia - A resting heart rate that exceeds the normal range.

T-wave - On an ECG, it represents the recovery of the ventricles.