Uncomplicated HSP includes the typical symptomatology of the disease: progressive lower leg muscle weakness (paraplegia) and increased leg muscle tone (spasticity). Patients initially exhibit symptoms early in the course of their life, displaying walking abnormalities, such as tripping or stumbling, due to a lack of coordination when walking. Feet paresthesias and bladder dysfunction may accompany the clinical symptoms mentioned above, but no other symptoms are evident [7].

Complicated HSP encompasses a variety of other crucial symptoms, including ataxia, dementia, hearing impairment, seizures, peripheral and optic neuropathy and ichthyosis. Some of the symptoms may not be caused by HSP itself, but manifest as a result of a comorbidity.

The disease is progressive and during the course of the years, many patients finally rely upon supportive equipment, such as wheelchairs or crutches in order to move [7]. Accentuated reflexes, difficulty in lifting one's toes and dragging of the feet are expected observations. it is important to keep in mind that some of the symptoms attributed to HSP may not be caused by the condition itself, but by another comorbidity.

• Weakness

  Hereditary Spastic Paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders with weakness and spasticity of the lower limbs as its main clinical feature. [omicsonline.org]

  Symptoms Of Uncomplicated Or Pure Type Of Hereditary Spastic Paraplegia- 2 Stiffness- Muscle and Joint Stiffness Weakness- Weakness in leg muscles observed. Balancing- Unintended tripping or falls are observed secondary to balance disorder. [epainassist.com]

  In the type II group muscle weakness, urinary symptoms and sensory loss were more marked. This form of the disease evolved more rapidly. [ncbi.nlm.nih.gov]

• Falling

  INTRODUCTION: Balance impairments are common in patients with hereditary spastic paraplegia and are among the most debilitating symptoms, as they frequently result in falls and fall-related injuries. [ncbi.nlm.nih.gov]

  This often leads to difficulties clearing the feet and may cause tripping or falling or compensations such as hip hitching to help ambulate. [ottobock.co.uk]

  Balancing- Unintended tripping or falls are observed secondary to balance disorder. Abnormal balancing is caused by muscle weakness and cerebellar malfunction associated with the hereditary spastic paraplegia/Strumpell-Lorraine Syndrome. [epainassist.com]

  A 16-year-old Caucasian boy started having progressive gait disturbance, and frequent falls at 12 years of age. He had normal achievement of motor milestones. [scielo.br]

• Difficulty Walking

  The hereditary spastic paraplegias (HSPs) are inherited neurologic disorders in which the primary symptom is insidiously progressive difficulty walking due to lower extremity weakness and spasticity. [ncbi.nlm.nih.gov]

  This leads to difficulty walking. As degeneration continues, symptoms worsen. [1] If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved. [rarediseases.info.nih.gov]

  The clinical picture is composed of difficulty walking, exaggerated deep reflexes, pathological reflexes such as the Babinski sign, sphincter disturbances and various degrees of weakness as well as sensory disturbances. [clinicaltrials.gov]

  Balance difficulty, often worse when walking in the dark or on uneven surfaces is not uncommon in individuals with HSP. Tightness in the legs and leg muscle spasm (often at night) are not uncommon. [rarediseases.org]

  The main symptom of HSP is progressive difficulty walking due to increasingly weak spastic leg muscles. [biomediclabs.com]

• Pathologist

  Orofacial/odontological treatment Speech and language impairments are to be diagnosed and treated by a speechlanguage pathologist. Oral motor training and stimulation may be relevant in cases of eating difficulties, speech impairment and drooling. [mun-h-center.se]

  PMID: 24603320 Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion [invitae.com]

• Muscle Spasm

  Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. [uniprot.org]

  A person may develop tightness in the leg muscles as a result of spasticity and may suffer from leg cramps and muscle spasms. [ottobock.co.uk]

  Hereditary (familial) spastic paraparesis is a group of rare hereditary disorders that cause gradual weakness with muscle spasms (spastic weakness) in the legs. [msdmanuals.com]

• Muscle Spasticity

  Lower motor neurons then carry the messages out to the muscles. This results in a progressive increase in muscle spasticity and weakness. [biomediclabs.com]

  Hereditary Spastic Paraplegia (HSP) is a group of rare, inherited neurological disorders. Their primary symptoms are progressive spasticity and weakness of the leg and hip muscles. [sp-foundationorg.presencehost.net]

  Many symptoms that are common in people with HSP are not directly caused by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes. Spasticity Spasticity is an increase in muscle tone with resulting stiffness. [emedicine.medscape.com]

• Leg Cramp

  A person may develop tightness in the leg muscles as a result of spasticity and may suffer from leg cramps and muscle spasms. [ottobock.co.uk]

  Reflexes become exaggerated, and leg cramps, twitches, and spasms occur, making leg movements stiff and jerky (called a spastic gait). Walking gradually becomes more difficult. [msdmanuals.com]

  Many patients with HSP may not get their required amount sleep, because of leg cramps or spasms or as a result of the frequent need to urinate during the night. Stress and depression 59. THANK YOU [slideshare.net]

• Foot Deformity

  Spasticity decreased bilaterally and the flexibility of her foot deformities improved to allow orthotic fabrication in subtalar neutral. Results were maintained at 12 and 16 months. [ncbi.nlm.nih.gov]

  Non-neurological manifestations may include ophthalmological abnormalities (cataracts, retinitis pigmentosa, macular degeneration), and orthopedic abnormalities (scoliosis, joint dislocation, and different foot deformities). [orpha.net]

  Spasticity may lead to foot deformities. Arm and hand function are often unaffected. Unstable balance and ataxia (impaired control of voluntary movements) occur. [mun-h-center.se]

  In case of prominent distal weakness affecting foot dorsiflexion it is reasonable to use ankle-foot orthoses. Secondary deformities such as scoliosis, tendon contractures and foot deformities may require surgical management. [scielo.br]

• Back Pain

  Back pain as a result of Hereditary Spastic Paraplegia can be helped by back strengthening exercises. Stretching Exercises- These exercises are beneficial for increasing range of motion and prevent development of cramps etc. [epainassist.com]

  Back-strengthening exercises may help to reduce or eliminate back pain (due poor gait, poor posture, use of a mobility device). Stretching exercises – These help to maintain or increase ROM and to reduce muscle cramps. Aerobic exercises – 51. [slideshare.net]

• Suggestibility

  Examination of intrafamilial correlation of age of onset in the dominant cases suggested that the disorder is genetically heterogeneous. [ncbi.nlm.nih.gov]

  Their father was said to be “a little lame,” suggesting that the mode of inheritance might be autosomal dominant ( Strumpell 1880 ). [medlink.com]

• Spastic Paraplegia

  paraplegia, autosomal recessive hereditary spastic paraplegias, autosomal dominant hereditary spastic paraplegias, and X-linked hereditary spastic paraplegias. [medlink.com]

  Key words: hereditary spastic paraplegia; spastic paraplegia; muscle spasticity; genetics; mutation RESUMO Paraplegias espásticas hereditárias (PEH) constituem um grupo de desordens geneticamente determinadas caracterizadas por espasticidade e paraparesia [scielo.br]

  Hereditary spastic paraplegia with a thin corpus callosum due to SPG 11 mutation. [neurologyindia.com]

  Klebe S, Depienne C, Gerber S et al : Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy. Brain 2012; 135 : 2980–2993. 10. [nature.com]

• Cerebellar Ataxia

  “Complex” spastic ataxia in which the cerebellar ataxia is a (sometimes variable) feature of a more complex syndromal picture. [link.springer.com]

  G11.0 Congenital nonprogressive ataxia G11.1 Early-onset cerebellar ataxia G11.2 Late-onset cerebellar ataxia G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia [icd10data.com]

  INTRODUCTION: The combination of cerebellar ataxia and spasticity is common. However, autosomal dominant genetic diseases presenting with spastic-ataxia are a smaller group. [ncbi.nlm.nih.gov]

  The recent identification of new genes and loci, however, has blurred the distinction between hereditary spastic paraplegias and other entities, such as cerebellar ataxias or leucodystrophies. [dx.doi.org]

• Spastic Gait

  For many subjects with an ATL1 mutation, spastic gait begins in early childhood and does not significantly worsen, even over many years; such cases resemble spastic diplegic cerebral palsy. [ncbi.nlm.nih.gov]

  The original description of hereditary spastic paraplegia was made by Strümpell in 1880. He described “a pure spastic movement disorder of the legs” in 2 brothers who developed a spastic gait at the ages of 37 and 56 years. [medlink.com]

• Lower Extremity Spasticity

  It is characterized by progressive lower extremity spasticity and weakness, dysarthria, distal amyotrophy, developmental delay, short stature, and subtle skeletal abnormalities. [ncbi.nlm.nih.gov]

  Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. [icd9data.com]

• Hyperreflexia

  From Wikidata Jump to navigation Jump to search genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs HSMN V familial spastic paraplegia Strümpell-Lorrain [wikidata.org]

  HSP is generally classified as pure when lower limb spasticity and weakness, hyperreflexia, extensor-plantar responses, decreased vibration sense at the ankles, bladder dysfunction, pes cavus and scoliosis are the only signs; if there are additional neurologic [omicsonline.org]

  Orthostatic intolerance, urinary symptoms, hyperreflexia in the biceps and knee jerk, and decreased proprioception in both limbs were observed on neurological examinations. [ncbi.nlm.nih.gov]

  Patients have spastic leg paresis, with progressive gait difficulty, hyperreflexia, clonus, and extensor plantar responses; some forms cause extraspinal neurologic deficits. [msdmanuals.com]

• Urinary Urgency

  Bowel urgency is less common but may occur. Medications such as oxybutynin may reduce urinary urgency. If urinary urgency is severe or accompanied by difficulty initiating urination, consultation with a urologist is recommended. [rarediseases.org]

  Urinary urgency was reported among the female carriers. MRS of both patients showed increased myo-inositol in the white matter, while decreased N-acetylaspartate was found exclusively in the oldest patient. [ncbi.nlm.nih.gov]

  Urinary urgency is also a common symptom which can be an early presenting sign. [bmcresnotes.biomedcentral.com]

• Urinary Incontinence

  HSP more frequently reported much problems on alternating constipation and diarrhea ( χ 2 (1) = 9.163, p χ 2 (1) = 11.032, p χ 2 (1) = 26.253, p Urinary problems 52 % confirmed urinary incontinence HSP more frequently reported urinary incontinence ( χ [doi.org]

  Some people also experience urinary problems; eg, incontinence or a sense of urgency even when the bladder is not full. [4] A study by Kanavin and Fjermestad found that of 108 adults with hereditary spastic paraplegia (HSP), 30.5% suffered from urinary [emedicine.medscape.com]

  No urinary incontinence was reported in the younger sister–sister pair. This was difficult to assess in the other pair because they were on diapers. [bmcresnotes.biomedcentral.com]

  During follow-up, 94% developed sphincter problems, manifesting as urinary as well as fecal incontinence in 44%. Obesity was seen in 14 patients in total (78%), of whom 9 were non-ambulatory. [nature.com]

A physical examination provides the initial vital information for HSP to be diagnosed. The most common disease type, a result of a mutated SPG4 gene, can also be diagnosed with genetic testing, both antenatally and postnatally.

Electrophysiology [8] can further assist in corroborating the diagnosis of HSP. Muscle tone can be evaluated, as well as the conduction ability of peripheral nerves and dorsal column. Patients often test absolutely normally in a nerve conduction test. However, evoked potentials exhibit a considerable delay in dorsal column fibers and corticospinal tracts. A Magnetic Resonance Imaging scan can reveal atrophic spinal cords and cerebral cortex.

HSP is incurable; various treatment can be applied to ameliorate the clinical picture and improve a patient's standards of living.

The first and simplest step is physiotherapy: patients are encouraged to strengthen their body and retain a near-to-normal muscular tone.

Drugs such as baclofen have also been administered, primarily with an aim to reduce leg stiffness and aid the patients is walking [9]. Surgical implants (pumps) may also be used in some cases: the direct administration to the spinal canal seems to be more beneficial to individuals with severe symptomatology or intolerance to per os administration of the drug. Other medications include diazepam, clonazepam, tizanidine, anticholinergics in cases of bladder dysfunction and botulinum toxin injections [10].

Various equipment such as ankle braces, crutches or wheelchairs (in severe cases) can also help the patient move independently.

It is important to note that each patient is individually treated and may receive further drug treatment, depending on the symptomatology of each particular case. Genetic counseling is also recommended to families of patients with HSP.

The conditions categorized under the term of hereditary spastic paraplegia are non-fatal. Patients have normal lifespans.

HSP is a rare condition of inherited diseases. Oddly enough, due to the various genetic mutations that cause the HSP phenotypes, the conditions can be inherited with an autosomal dominant, autosomal recessive and X-linked pattern of inheritance [2] [3]. The genes involved in many disease types have been mapped and up to this day, 18 mutations are known to be passed down with an autosomal dominant pattern, another 17 with a recessive pattern and 3 types are inherited in an X-linked way [3].

Regarding the possibility of having an offspring with HSP when a parent is affected by it, physicians have to keep in mind the basic rules of gene inheritance:

• Autosomal dominant pattern: only one defective gene copy needs to be present for an individual to suffer from the condition. Should this pattern of inheritance be present, there is a 50% chance that a parent who is affected by it will pass it down to their children. The possibility refers to each pregnancy separately.
• Autosomal recessive pattern: two defective copies of the gene need to be present for the child to exhibit symptoms. In this case, an affected parent and a healthy parent who is not a carrier, will give birth to carrier offspring and in no case a child that will develop the disease. If both parents are carriers, there is a 25% possibility that the offspring will suffer from the disease as well and 50% chance that they will be born as carriers themselves.
• X-linked pattern: The defective gene is located on the X chromosome. A carrier mother has 25% chance of having a carrier or non-carrier daughter, 25% chance of having an unaffected  son and also 25% chance of giving birth to a son that will suffer from the disease.

HSP has an extremely variable clinical presentation; in order for an accurate prevalence to be calculated, there should be a union of criteria and methodology, which is not always the case. Due to this fact, prevalence has been estimated at approximately 2.7-4.3 per 100,000 in 3 different locations in Italy and 2 per 100,000 in Portugal [4]. The single report that suggested the highest prevalence of HSP calculated it to be 9.6 per 100,000 in Cantabria, in Spain [5].

Even though the genetic mapping of many HSP types has been successfully completed, the exact pathogenesis of the conditions has yet to be understood [6]. This group of conditions is perceived as a result of a progressive, degenerating process that affects the upper motor neurons, namely the nerve cells that are located in the brain and spinal cord and are responsible for the coordinated contraction of muscles. The lower motor neurons, responsible for the execution of a motion, remain functionally intact, but fail to receive the proper order from the higher counterparts, in order for a complete, normal movement to be carried out.  

Hereditary spastic paraplegia is an inherited condition of unknown causes. there is no known way to prevent its occurrence.

Hereditary spastic paraplegia (HSP) is not a single condition, but rather a group of closely linked diseases with a similar phenotype. Patients exhibit fluctuating symptoms and even individuals with the same condition type may experience quite distinct symptomatology. Even though symptoms vary greatly, the common axis between different spastic paraplegias includes a progressively increasing tone of the leg muscles otherwise termed spasticity, and a gradually developing loss of muscle control, also in the legs (paraplegia) [1].

Based on the clinical picture, there are two types of HSP. The uncomplicated type features the aforementioned symptomatology without other signs of major neurological complications. Symptoms that may arise as well include bladder dysfunction or leg paresthesias. On the other hand, the complicated HSP type includes severe neurological symptoms, such as ataxia, epileptic activity, cognitive impairment and skin conditions, which further complicate the paraplegic and spastic symptomatology.

HSP is a group of inherited conditions that are caused by genetic mutations that evince great variability. The pattern of inheritance may be X-linked, autosomal recessive or autosomal dominant. Loss of muscle control and leg spasticity are the predominant, common symptoms, which gradually develop. Each patient experiences symptoms to a certain degree and most of the individuals ultimately require some kind of assistance in order to move, such as crutches or a wheelchair.

Diagnosis is achieved upon clinical examination, evaluation of muscle tone, genetic testing and electrophysiologic studies. Imaging techniques can further corroborate the suspicion of HSP. Even though no cure is available for HSp patients, they can be treated with baclofen for spasticity, anticholinergics, diazepam, clonazepam and other drugs, with an aim to alleviate some of the symptoms.

Hereditary spastic paraplegia is a group of conditions with a similar symptomatology. Characteristic symptoms are weakness in the muscles of the legs and subsequent stiffness. 

The causes are unknown. The diseases is passed down with various patterns, such as an autosomal recessive or dominant way or an X-linked pattern. up to this day, around 31 different mutations have been identified, but many more remain unknown to the scientific community.

There are two types of HSP: complicated and uncomplicated. the uncomplicated type is the simplest disease type and includes:

• Leg stiffness
• Paraplegia (progressive loss of leg muscle control and weakness)
• Bladder dysfunction
• Leg paresthesias. Paresthesias are weird sensations experienced, in this case, in the legs, such as pins and needles, numbness, heat or cold.

The complicated type of HSP includes all the symptoms described above, plus cognitive impairment (mental retardation, memory problems, speech problems), difficulty in maintaining balance when walking, epilepsy and other serious neurological defects.

Symptoms related to HSP are observed during childhood, starting with cramping legs, imbalanced and strange gait, tripping and stumbling. Patients often experience tiredness when trying to walk because their feet muscles are weakened. The problems evolve gradually and progressively, even though their greatly vary amongst individuals, even those who have the same genetic mutation. Ultimately, some kind of walking device is usually required, such as crutches, braces or wheelchair, to facilitate movement.

Diagnosis is made mainly upon exclusion, i.e other conditions that cause the same symptoms have to me excluded. Genetic testing may also be carried out, but will only diagnose the most common mutation known. An electrophysiologic study may help to confirm a potential HSP diagnosis and an MRI scan may reveal brain malformations that are compatible with the condition.

There is no way to cure HSP. Patients follow conservative treatment in order to improve their symptoms, such as physiotherapy or drugs to help their muscles relax. Medications may be taken orally or injected in the muscles (IM).

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