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What is Ataxia

Have you ever wondered how we easily grab that flask on the table? or how we effortlessly climb a few flight of stairs without missing a step and falling face down? The Cerebellum is a part of the human brain that controls and coordinates these kinds of movements. It fine-tunes the signals received from the brain, spinal cord and other structures and delivers a polished result.

Ataxia occurs because of involvement to the cerebellum. It leads to uncoordinated voluntary movements and loss of balance. Spinocerebellar (SCA) is a type of Ataxia that affects the cerebellum, its surrounding structures and its connection to the spine. The most characteristic feature is the walking pattern that mimics the "drunkard’s gait". In addition, the hand movements, speech and eye movements are also uncoordinated.

Ataxia could be broadly classified into Cerebellar Ataxia and Spinocerebellar Ataxia.

Cerebellar ataxia – This type of ataxia occurs due to abnormality in the part of the brain called cerebellum.

Spinocerebellar ataxia – This type of ataxia occurs to abnormality in cerebellum as well as spinal cord

No definite cause of Cerebellar ataxia has been identified. It can be progressive starting in childhood or teenage or 3rd / 4th decade of life. Most often ataxia is associated with atrophy (shrinking) of cerebellum.

For SCA some genetic causes have been identified. The first ataxia gene was identified in 1993 and was called "Spinocerebellar ataxia type 1" (SCA1). Subsequently, as additional dominant genes were found they were called SCA2, SCA3, and so on. Usually, the number followed by SCA refers to the order in which the gene was found. Identifying the different types of SCA requires genetic testing. There are around 29 types of SCA. Few of the types are as follows:

SCA1

It occurs at around 40 years of age. The person commonly experiences saccades (jerky eye movements) and difficulty in producing speech. The symptoms are slowly progressive in nature.

SCA2

It usually affects people in the age group of 30-40 years. Some of the features include rigidity of the muscles, slowness in movements, weakness of eye muscles and difficulty in swallowing.

SCA3

This is the most commonly seen subtype in the adult population. Like SCA1, this also occurs around 40 years of age and above. It is also called Machado-Joseph disease. Problems include rapid eye movements on attempting to move the eyes, Parkinson-like symptoms, muscle twitches and at times sensory problems in hands and feet.

SCA4

This is a late onset type and usually occurs in 4th to 7th decade of life. It is characterized by loss of muscle responses (reflexes), weakness of muscles and sensory problems.

A person suffering from Ataxia face difficulties in all the performance areas and there is involvement of most of the body systems. Some of them are:

  • Difficulty in performing coordinated activities with arms, legs and trunk.
  • Walking in a steady pattern is affected
  • Frequent fall history
  • Abnormal eye movements
  • Changes in speech clarity and other communication difficulties
  • Difficulty in performing fine motor skills
  • Gradually increasing dependency for performing self-care activities
  • Other associated problems like headaches, dizziness etc.
  • Change in behavior, increased anxiety etc.

Initial Phase:

  • Poor limb coordination.
  • Dysarthria - slurred and slow speech that is difficult to produce. The patient may also have difficulties controlling volume, rhythm, and pitch.

Later Phase:

  • Swallowing difficulties, this may sometimes result in choking or coughing.
  • Facial expressions become less apparent.
  • Tremors - parts of the body may shake or tremble unintentionally.
  • Nystagmus - involuntary, rapid, rhythmic, repetitive eye movement. Movements may be vertical, horizontal, or circular.
  • Cold feet - because of a lack of muscle activity.
  • Problems with balance.
  • Walking difficulties - in severe cases, the patient may need a wheelchair.
  • Vision problems.
  • Hearing problems.
  • Depression - as a result of having to live and cope with the symptoms.

There is no curative medical treatment available for ataxia.

  • Occupational therapy - the occupational therapist can help the patient’s independence around the house and at work; this may involve some home adaptations, wheelchair assessments, and making the kitchen more practical for the patient. Prescribing appropriate adaptive devices that help the patient for independence like the use of a cane (walking stick), reachers, modified utensils etc.
  • Speech therapy - the speech therapist can help with swallowing, coughing, choking, and speech problems. If speech becomes very difficult, the speech therapist can help the patient learn how to use speech aids.
  • Physical therapy - a physical therapist can help maintain strength and improve mobility.
  • Counseling – patients and family members with ataxia commonly become frustrated and depressed. This usually results from having to cope with some symptoms that affect physical mobility and coordination. Therefore, counseling is important for both patients and their family members.
  • Medication – Some of the drugs are usually prescribed for muscle spasms, abnormal eye movements and for managing mood and emotional changes.

Neurogenic potential of BMMNCs and functional potential of the regenerated neural cells is currently being tested in various clinical trials. The pathology of SCA is believed to be due to autoimmunity towards the polyglutamine complexes formed by the mutant gene, whereas in cerebellar ataxia there is progressive degeneration of nerve cells in cerebellum. MNCs have shown immunomodulatory effects. Cellular transplantation has also demonstrated anti-inflammatory effects. Preclinical experiments in animals suggested that, reduction of Vascular Endothelial Growth Factor (VEGF) levels observed in SCA contribute to the SCA pathology. They also observed reduced density and shorter lengths of cerebellar blood vessels. VEGF is not only an angiogenetic but also a neurotrophic factor and reduced levels VEGF leads to stunted growth and limited repair of cerebellar neurons in SCAs and cerebellar ataxias. BMMNC fractions on artificial growth media have been found to secret VEGF along with various other growth factors and cytokines. These factors have been shown to give rise to various paracrine effects like immunomodulatory effect, anti-inflammatory effect, stimulation of resident stem cells, which in turn enhances tissue perfusion. The various paracrine effects of cellular transplantation help alleviate the disease pathology.

We performed a study to demonstrate the effect of autologous bone marrow mononuclear cells in 91 cases of cerebellar ataxia. Symptoms such as co-ordination, ambulation, hand functions, stamina/fatigue, trunk balance and standing were analysed. On follow up, 93.4% of patients showed improvements while 6.6% showed no improvement. 49.45% patients showed mild improvements, 39.5 % moderate improvements and 4.3% showed significant improvements.

Figure 1: Improvements seen in cerebellar ataxia patients after intrathecal administration of autologous BMMNCs.

Figure 2: PET CT Scan showing improved metabolic activity which is indicated by increased orange area in the cerebellum after stem cell therapy as indicated by the circles.

Published data

Cellular transplantation may modulate disease progression in spino-cerebellar ataxia – a case report

A 33 year old female with SCA was treated with autologous BMMNCs intrathecal transplantation followed by standard rehabilitation. She had severe impairment of dynamic balance, coordination, speech, gross and fine motor control. Ambulation was dependent; requiring support from two people with an ataxic gait. Functionally, she scored 86 on Functional independence measure (FIM) and 62 on Ataxia rating scale. On follow up at six months after the transplantation there was a significant improvement in handwriting, fine motor activities, standing dynamic balance and intelligibility of speech. There was an improvement in the cerebellar signs and symptoms and outcome measures like Modified International co-operative Ataxia rating scale (MICARS). The MICARS score reduced from 62 to 58.

Q1) What is Spinocerebellar ataxia?

Spinocerebellar ataxia (SCA) is a progressive neurological disorder characterized by difficulty in walking due to incoordination, involuntary movements of limbs and eyes, and difficulty in speaking.

Q2) What are the possible long term complications?

  1. Incoordination: Since SCA is a neuro degenerative condition, it could lead to difficulties in performing coordinated movements.
  2. Loss of balance while walking on uneven surfaces, or climbing stairs are common.
  3. Falls could occur frequently because of the incoordination and imbalance.
  4. Poor Speech Clarity could lead to problems in expressing needs and communicating.

Q3) Is SCA curable/recoverable?

Since SCA is progressive, the treatment options available are limited. The goal is to arrest or slow down the progression of the disease. This has been achieved in our patients who have undergone Stem Cell Therapy followed by a strict regimen of Rehabilitation.

Q4) Would my life be normal?

A composite routine of Physiotherapy, Occupational Therapy, Speech Therapy, Psychology, etc. can improve the overall quality of life. With these therapies that focus on your problem areas, you would find yourself capable of doing a lot of tasks that were much difficult to perform before. Yes, you could tell yourself and the world that you can function better.

Q5) What is the role of stem cell therapy in a patient with SCA?

As in other incurable neurological disorders, stem cell therapy along with rehabilitation helps in recovery of neurological deficits. It also helps in improving other problems, which are not improved by rehabilitation alone.

Our experience suggests that, cognition improves, coordination becomes better speech improves and risk of falls reduces along with other motor/physical functions.

Q6) How does stem cell therapy work?

The biological task of stem cells is to repair and regenerate damaged cells. Stem cell therapy exploits this function by administering these cells in high concentrations directly in and around the damaged tissue, where they advance its self-healing and repair.

Q7) Are there ethical concerns surrounding adult stem cell research and therapy?

Bone marrow transplantation has been used successfully for genetic disorders of blood, such as sickle cell anemia, thalassemia, as well as cancers such as leukemia. Since our therapy uses these very cells, which are harvested from the patient’s own body (autologous cells), there are no major ethical concerns. Ethical concerns are primarily on the use of embryonic stem cells (which we do not use).

Q8) Does the treatment have any side effects?

Stem cell therapy is minimally invasive and reasonably safe. None of our patients have shown any neurological deterioration so far in connection with the stem cell therapy itself. Some side effects, such as headache (spinal headache) lasting 3-4 days which is generally self-limiting, neck/back pain, vomiting, some mild rash or pain at the site of bone marrow aspiration/stem cell injection may occur. However, like any other medical or surgical treatment unexpected complications are always a possibility. These complications may be related to the medicines given, the stem cell procedure, the anesthesia, and the rehabilitation or to any of the preexisting medical or neurological conditions.

Q9) How long will it take me to know that I have benefitted from the treatment?

Maximal improvements are seen around 3-6 months after the treatment. However, in many patients there are slow progressive improvements that continue for several months/years later. Most patients do show some immediate improvements also i.e. before the discharge, in some of their symptoms.

Q10) Is the transplantation of the stem cells done once or more than once?

The decision to do the therapy a second time is taken after seeing the progress/improvements after the first therapy. If the patients show some encouraging improvement, then the case is reviewed by the entire medical and rehabilitation team and a second treatment may be recommended. This may be done anytime between 3-6 months of the first therapy.

Q11) Can other treatments be taken at the same time?

We will review what other medications the patient is already on. In most cases, we do not discontinue any already going on treatment. However, this is decided on a case by case basis. Blood thinners like aspirin, clopidrogel, warfarin, etc. needs to be stopped. Please inform us about any medications you are taking beforehand.

This is difficult to predict, since this a new therapy. It depends on multiple factors such as age of patient, type of illness, duration of illness and extent of rehabilitation taken after the treatment. It is important to note that at NeuroGen we give no assurances or guarantees of any definitive improvements or results. However, from our past clinical results show that 94.22% of patients showed overall improvement. Improvements were seen in higher mental functions, posture, trunk activity, upper limb activity, lower limb activity, coordination, oromotor, ambulation and Activities of Daily Living.

Our data is regularly published in various medical and scientific journals (available for reading on our website). You are strongly advised to study these before proceeding with treatment.

Stem Cell Therapy helps her to regain her skills

Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disorder. It is mostly hereditary in nature and can affect either female or male members of the family. It mainly involves the brainstem, cerebellum, and spinal cord areas of the nervous system showing features of incoordination and imbalance. Likely, a 33-year-old female diagnosed with SCA visited our centre whose symptoms started at 18years of age. She came with problems such as intentional tremors that interfered with her activity performance, balancing difficulty, difficulty in climbing stairs and used to get tired easily. She also reported to have frequent falls, difficulty in performing fine activities, poor speech clarity, and urinary incontinence. These symptoms continued to worsen day by day even though she was under regular treatment. Therefore, she chose to undergo stem cell therapy. In the first week following the therapy, her tremors had reduced and her walking difficulties had minimized. By around three months, her sitting balance had improved and her speech was clear. Gradually over a period of 8 months her tremors had reduced, her coordination had improved, fine motor skills were better and her trunk and neck was more stable. She also experienced improvements in her handwriting, her ability to reach out for objects and her balancing abilities.