Hereditary Spastic Paraplegias ( Hsps )

Spinal muscular atrophy may present itself in various forms, affecting every stage of life. Consequently, this stretches from the affected fetus exhibiting joint contractures, to a young child who cannot independently sit (type I) and to a young

This disease affects the nerve cells by enabling them to send electric impulses to the muscles which ultimately makes the muscle wither away and stop working. The nerves targeted are actually

Patients will report to physical therapists with a multitude of impairments throughout the progression of the disease. The most prominent impairments will present during cerebellar testing. Patients will show signs of dysmetria, dysphasia, dysdiadochokinesia, and ataxia primarily as a result of the atrophy and damage to the cerebellum. Instability and lack of postural control will be demonstrated during the Romberg's test. Additionally, cranial nerve testing will have positive results for many cranial nerve palsies such as CN III, V, VII, IX, and XII. Patients show weakness in their trunk and extremities during the manual muscle testing. Vestibular testing will result in abnormal VOR, saccades, smooth pursuits and nystagmus. As a result of these impairments, patients experience functional limitations. Primarily, these patients are considered to be “high fall risks,” which ultimately decreases their independence due to weakness, instability and decreased postural control. These patients will feel uncomfortable in many situations and be unable to function independently in the community. This creates an increased risk for further injury. Due to the dysmetria and weakness, patients will also experience difficulty with their daily living skills, such as maintaining proper hygiene; They will have trouble bathing themselves and brushing their teeth without assistive equipment. PT interventions can help minimize and control these limitations. The implementation of balance training and assistive devices will be imperative interventions for an individual to modify and adapt to their gait

Primary lateral sclerosis is a very rare form of MND in which people experience spasticity but do not experience muscle wasting or fasciculation’s.

The spinal motor neurons undergo an aging-related gradual loss due to the interaction of multiple factors; the neurons undergo a programmed cell death along with a decrease in signaling by growth factors and protein uptake. This process leads to the denervation of muscle fibers. The surviving motor axons or motor end plates can send some collaterals to innervate the denervated muscle fibers which explains the formation of enlarged motors end

Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s disease, is a neurodegenerative autoimmune disease. This means that the neurons ( nerve cells of the brain and spinal cord), particularly the ones that control voluntary muscles (motor neurons), degenerate and die. Naturally, motor neurons in the brain send signals to the motor neurons in the spinal cord, which in turn, sends signals to the muscles. However, the degeneration and death of these neurons (upper and lower motor neurons) doesn’t allow the body to transmit signals to permit the movement of muscles. This eventually causes the weakening of the muscles, and the brain’s loss of controlling voluntary muscle movement. By this, people lose their ability to speak, walk, and breathe.

Hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders, which are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may be also produced by inborn errors of metabolism [1,2]. Next generation sequencing (NGS) is helpful for investigating patients in whom genetics does not fully meets the clinical presentation. We performed NGS in adult twins and found compound pathogenic mutations in MTHFR and POLG1 genes, which were consistent with metabolic changes, including hyperhomocysteinemia decreased activity of MTHFR and mitochondrial respiratory chain.

In 1995 a French group of researchers discovered that SMA is autosomal recessive disorder due to loss of the survival motor neuron protein gene (SMN) (Lefebvre et al., 1995). Through experimentation the researchers discovered two copies of the SMN gene in chromosome five [chr 5q13.2]: telomeric and centromeric SMN copies. Experimentation proved that loss of the telomeric SMN (today known as SMN1) and not loss of its centromeric counterpart, SMN2, resulted in SMA.

Some of these strategies are promising and capable of restoring some motor function in spinal muscular atrophy models, especially increasing SMN protein production via upregulation of the SMN2 gene. However, this is a more global approach and these drugs have been shown to cause toxic side effects in other cells. Another more specific approach involves antisense oligonucleotide (AON) technology to modulate mRNA splicing in order to create additional functional SMN protein from the SMN2 gene as compared to the typical 10-30%. This has been shown to be effective in mice but the issue is the need for an efficient delivery system in humans. Another promising treatment strategy reprograms fibroblasts into induced pluripotent stem cells to compensate for the damaged motor neurons. This has been promising in the mouse model and may translate better to human motor neurons than other tactics. Some difficulties in developing effective treatments include unwanted toxic side effects and manipulating pharmacokinetics to allow for effective treatment. Scientists are working to develop a better understanding of the genetic mechanism of the disease and develop more efficient strategies of delivering drugs4. In addition,

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease (ALS Association, 2016). A neurodegenerative disease is a disease in which nerve cells are damaged or killed. In this particular case, the damaged motor neurons affect voluntary movements (Newton et al., 2000). Amyotrophic lateral sclerosis, commonly known as ALS for short, got its name from the Greek language. By breaking the name into a-myo-trophic; “a” means no, “myo” refers to the muscle cells, and “trophic” refers to nourishment (ALS Association, 2016; Gulli & Veillette, 2002; Hains, 2006). “Lateral” indicates the area of the spinal cord where the nerves are being affected (Gulli & Veillette, 2002). “Sclerosis” refers to the scarring and hardening of the spinal cord

This protein has been shown to activate the epidermal growth factor receptor (EGFR) thereby inhibiting neurite outgrowth and axon regeneration (Schachtrup et al., 2007). In addition to plasma proteins, there is invasion of blood circulating inflammatory cells into the spinal cord through the disrupted BSB. Since spinal cord is considered as an immune-privileged or immunologically quiescent site, the sudden influx of immune cells dramatically alters the regulation of the inflammatory response in the injured spinal cord (Trivedi et al., 2006). This dysregulation of the inflammatory response plays a major role in enlargement of tissue damage in the secondary phase of the injury. As such, it is thought that the initial damage to the local blood vessels and BBB is decisive for the disruption events that cause the secondary phase of injury (Mautes et al., 2000a, Mautes et al.,

Axonal degeneration does have a significant impact on many neurodegenerative diseases. Their research found that this particular pathway, Sarm1-MAPK pathway, may be a common pathway for different types of axonal degeneration, not just from traumatic injury. If the main pathway or underlying mechanism that drives these diseases is uncovered and understood, then this can lead to creating different methods to protect synapses and axons in these diseases. Other research can focus on trying to inhibit the Sarm1-MAPK pathway, or at least inhibit distinct components within it. Their research is pertinent to finding a cure or possible treatments for many of these diseases. This will have multiple implications on society, medicine, and the quality of life for many people suffering with the many debilitating symptoms associated with these diseases.

The spasticity is considered the main problem as it will cause the affected muscle constantly in contracted state, hence limited the range of movement of the affected joint. Spasticity is defined as a velocity dependent increased resistance to passive muscle stretch, or alternatively as inappropriate involuntary muscle activity associated with upper motor neuron paralysis (GOLDSTEIN, 2001 and SANGER et al., 2003). Muscle over-activity produces muscle shortening and muscle shortening increases spindle sensitivity. Thus, Stephanie will feel extreme pain and struggle whenever the affected muscle is being lengthened unconsciously or fast. This will severely affect her functional activity like not able to move freely as a normal child. For example, Stephanie already has grade 3 spasticity of her both ankle plantar flexors while grade 2 for both hip adductors and internal rotators. These constantly tighten muscles already severely affect her from

The spinal cord is a major channel in the body where motor and sensory information travels from the brain to the body. It has white matter that surrounds a central gray matter. The gray matter is where most of the neuronal cells are located. Injury to the spinal cord will affect the conduction of information across any part of the spinal cord where the damage is located (Maynard et al., 1997). This will often result in permanent disability of a certain muscle or region of the body (Meletis et al., 2008) and a loss of tissue where the damage is located (Peng et al., 2009). As of now, there is no treatment for spinal cord injury expect for steroids. All steroids can do is provide protect of the spinal cord from

Introduction: A long-term degenerative neurological condition (LTDNC) is a term used to describe diseases that affect the nervous system leading to its degeneration. Conditions such as Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis etc. are all categorized by impairment in brain, nerve and spinal cord pathway cells (Canadian Institute for Health Information, 2007). Due to such disruptions, the nerve signals between the brain and the body are affected which result in problems with walking, controlling movement, balance, full or partial paralysis, breathing and talking problems, occurrence of seizures, lack of bladder and bowel control at later stages, and even problems with the heart (Canadian Institute for Health Information, 2007). In 2011, the Canadian Institute for Health Information reported that Canada has one of the highest incidences of multiple sclerosis (MS) in the world, where approximately 93,500 individuals are currently affected. Despite the prevalence of the disease, there is still much that remains unknown. According to the 2012 statistics from the ALS Society of Canada, the number of new diagnoses per year is