Spastic paraplegia is roughly defined as the weakness of the lower limbs accompanied by neurological deficits of the sensory, motor, and autonomic nervous system [1] [2]. Causes of spastic paraplegia are diverse. Ischemia of the spinal cord, from either damage or obstruction of the blood vessels supplying the lower portion of the spinal cord (the posterior and anterior spinal arteries), can arise from atherosclerosis, the formation of aneurysms, dissections, or trauma [1] [2] [3] [4] [5]. Conversely, hemorrhagic events (epidural, subdural, subarachnoid hemorrhage or hematomyelia) are important vascular disorders as well, whereas a number of inflammatory and infectious processes (spondylodiscitis, myelitis, abscesses in the epidural/subdural spaces, multiple sclerosis, etc.), but also genetic diseases (adrenoleukodystrophy) affecting the spinal cord might manifest with spastic paraplegia [1] [5] [6]. In addition, surgery should also be included as a possible etiology [1] [2]. Apart from weakness and impaired motor and sensory activity of the lower limbs, loss of bladder and anal sphincter control, as well as gait disturbances, are hallmarks of spastic paraplegia [1] [6]. Symptoms sometimes appear after minutes (in the case of vascular events), or days and even weeks after an infectious or inflammatory process is responsible for spinal cord damage (in which case fever frequently accompanies neurological signs) [1], while a transient clinical course is also described [2]. Spastic paraplegia can be severely debilitating and result in a marked quality of life reduction, and some studies have implicated the psychological burden of this condition in many patients [7].

• Asymptomatic

  The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. [ncbi.nlm.nih.gov]

  Sensory neuropathy either can be asymptomatic which detect only by clinical examination, childhood onset or adult onset. Chronic painless cutaneous ulcers and neuropathic bone resorption found to be occur in some patients in their early childhood. [medicaljoyworks.com]

  For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene mutation in an affected family member. [mayomedicallaboratories.com]

  The phenotype was one of pure HSP with a wide range of disease severity with some patients requiring a wheelchair whereas others remained asymptomatic at the age of 40 years. [jnnp.bmj.com]

• Swelling

  Nonfunctional m-AAA proteases cause a build up of unusable proteins in the mitochondria of nerve cells, which can result in swelling of the cell, reduced cell signaling, and impaired cell movement, leading to the major signs and symptoms of spastic paraplegia [ghr.nlm.nih.gov]

  […] a person’s quality of life Medical treatments for paraplegia and quadriplegia include: Surgical procedures Doctors may use emergency surgical procedures to treat primary causes of central nervous system damage, such as: blocked or bleeding arteries swelling [medicalnewstoday.com]

  […] www.spinalcord.org American Spinal Cord Association 2020 Peachtree Road, NW Atlanta, Georgia, 30309-1402 Phone: 1- 404 - 355-9772 Web Address: www.asia-spinalinjury.org CONTACT A CAREGIVER IF: You have signs and symptoms of a DVT, such as: Tenderness, pain, or swelling [drugs.com]

  Both wild-type and mutant axons showed swellings containing mitochondria and clusters of vesicles resembling synaptic vesicles ( Figure 7I ; Video 8 ). [elifesciences.org]

  Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech 2013;6:72-83. [ Links ]. Hedera P, Eldevik OP, Maly P, Rainier S, Fink JK. [scielo.br]

• Pathologist

  The treatment team may include an orthopedist, physical therapist, occupational therapist, speech and language pathologist, social worker, or psychologist. You are an important member of the team, too. Leave A Legacy! [sp-foundation.org]

  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]

• Severe Pain

  Spasms can also cause pain for many people, especially those with neuropathic pain. [spinalpedia.com]

  Besides those with spasticity, intrathecal administration is also used in patients with multiple sclerosis who have severe painful spasms which are not controllable by oral baclofen. [hereditaryspasticparaplegia.wordpress.com]

• Impaired Balance

  Other symptoms may include: Mild gait abnormalities (ataxia) Impaired balance and coordination Peripheral neuropathy Deafness and/or impaired vision Presence of seizures (epilepsy) Rarer cases may exhibit dementia and cognitive impairments including learning [news-medical.net]

• Muscle Spasticity

  It is accompanied by irritability and spastic contractions of the leg muscles. spastic paraplegia Paralysis of both lower limbs with muscle spasm. This may be due to diseases of the brain or spinal cord, spinal nerve roots or peripheral nerves. [medical-dictionary.thefreedictionary.com]

  Individuals report various levels of improvement in spasticity levels of leg, arm, and bulbar (speech/swallowing) muscles. In extreme cases of spasticity, some individuals benefit by botulinum toxin, which is injected directly into the muscle. [sp-foundation.org]

  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-foundation-org.presencehost.net]

• Muscular Atrophy

  atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type I [Werdnig-Hoffman] G12.1 Other inherited spinal muscular atrophy G12.2 Motor neuron disease G12.21 Amyotrophic lateral sclerosis G12.22 Progressive bulbar palsy G12.23 Primary [icd10data.com]

  SPG17 is a motor neuron disease overlapping with distal spinal muscular atrophy type 5. [uniprot.org]

  Duchenne-Erb paralysis - Synonym(s): Erb palsy Duchenne-Erb syndrome - Synonym(s): Erb palsy Erb atrophy - a form of progressive muscular atrophy in which the disease begins in the muscle and not in the spinal centers. [medical-dictionary.thefreedictionary.com]

  Atrophy with Pyramidal Features, Autosomal Dominant — Spastic Paraplegia, Hereditary, Autosomal Dominant — Hereditary, Spastic Paraplegia, Autosomal Dominant — Charcot-Marie-Tooth Disease with Pyramidal Features, Autosomal Dominant — Charcot Marie Tooth [mesh.kib.ki.se]

• Dysarthria

  This syndrome is not only characterized by spasticity and weakness in the lower limbs, but also with dysarthria, mental retardation or mild developmental delay, and muscle wasting or muscle atrophy. [en.wikipedia.org]

  Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. [ncbi.nlm.nih.gov]

• Hyperreflexia

  This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. [ncbi.nlm.nih.gov]

  Neurologic examination of individuals with this mutation may show dysmetria in the upper extremities, hyperreflexia, distal amyotrophy and ankle clonus, in addition to spasticity, weakness and dysarthria. [en.wikipedia.org]

  People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. [icdlist.com]

  People with this form of spastic paraplegia may also have hyperreflexia in the arms, dysarthria, dysphagia, nystagmus, mild hearing loss, scoliosis, foot arch elevation, sensory neuropathy, motor neuropathy and amiotrofia. [ivami.com]

• Clonus

  This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. [ncbi.nlm.nih.gov]

  Neurologic examination of individuals with this mutation may show dysmetria in the upper extremities, hyperreflexia, distal amyotrophy and ankle clonus, in addition to spasticity, weakness and dysarthria. [en.wikipedia.org]

  The knee-jerk is excessive and ankle-clonus is easily obtained. In the advanced stage, if the disease has extended high up the cord, the upper extremities become involved. [henriettes-herb.com]

  Increased muscle tone Involuntary movements Spasms (quick and/or sustained involuntary muscle contractions) Clonus (series of fast involuntary contractions) Pain or discomfort Less ability to function Problems with care and hygiene Abnormal posture Contracture [my.clevelandclinic.org]

• Nystagmus

  A 29-year-old man developed progressive spastic quadriplegia from early childhood with dysarthria, ataxia, dysphagia, and intellectual delay, but he displayed no nystagmus. [ncbi.nlm.nih.gov]

  Some difference of opinion exists 4,5 regarding the full range of clinical manifestations of spastic paraplegia, but families have been reported with mental defect, optic atrophy, nystagmus, ataxia, seizures, rigidity, muscle atrophy, kyphosis, pes cavus [doi.org]

  […] chondrocytes Arnold-Chiari Malformation ● Autosomal Recessive or Sporadic ● With Syringomyelia Nosology: Chiari malformation Type 2 Anatomy: Cerebellar tonsils herniate through foramen magnum Clinical Onset: Childhood & Adult Brainstem signs Downbeat nystagmus [neuromuscular.wustl.edu]

  Neurological features may include cerebellar dysfunction (ataxia, nystagmus, tremor), axonal or demyelinating peripheral neuropathy (sensory and/or motor disturbances), cognitive impairment (dysexecutive syndrome, dementia), sensory impairment (optic, [orpha.net]

  People with this form of spastic paraplegia may also have hyperreflexia in the arms, dysarthria, dysphagia, nystagmus, mild hearing loss, scoliosis, foot arch elevation, sensory neuropathy, motor neuropathy and amiotrofia. [ivami.com]

• Lower Extremity Spasticity

  If symptoms begin later it may progress slowly and steadily.Progressive lower extremity spastic weakness is a characteristic feature of pure HSP.. [medicaljoyworks.com]

  […] characterized by progressive, usually severe, lower extremity spasticity and weakness. [flybase.org]

  Pure HSPs are characterized by slowly progressive lower extremity spasticity and weakness, often associated with urinary disturbances, and deep sensory abnormalities (reduction of lower extremity vibration sense). [orpha.net]

  Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. [molbiolcell.org]

Because of the fact that numerous conditions comprise this neurological syndrome in its clinical presentation (but also because time is of the essence when it comes to neurological injury), it is necessary to conduct a rapid but comprehensive clinical, laboratory, and imaging workup. Firstly, physicians should a obtain a detailed patient history that reveals preexisting disorders or events (eg. trauma) and assesses the course and progression of symptoms, whereas a properly conducted neurological examination (evaluation of sensory and motor function) can be sufficient to recognize spastic paraplegia [1]. As soon as clinical suspicion is raised, imaging studies of the thoracic and lumbar spine in the form of magnetic resonance imaging (MRI), particularly contrast-enhanced and diffusion-weighed imaging (DWI), must be employed [1] [5]. A lumbar puncture is also a key component of the diagnostic workup in patients with spastic paraplegia, as it can provide clear indications whether an infectious or inflammatory process is active, by showing an increased cell count (pleocytosis) and predominance of neutrophils/lymphocytes, while the content of protein and glucose in the cerebrospinal fluid is equally important [1]. If the diagnosis is still not conclusive, imaging studies should cover the endocranium and evoked potentials may be necessary, in order to exclude demyelinating diseases [1].

It was a three-treatment crossover study with randomization of the six different sequences of the three-treatments. [frontiersin.org]

Treatment There are no specific treatments to prevent, slow, or reverse HSP. Symptomatic treatments used for spasticity, such as muscle relaxants, are sometimes helpful. [brainfacts.org]

As of now, there is no clear cut treatment for Hereditary Spastic Paraplegia or Strumpell-Lorraine Syndrome but some of the treatments mentioned are found to be useful. [epainassist.com]

Prognosis Prognosis depends on the phenotype (pure/complex form), genotype, and is highly variable due to incomplete penetrance and variable gene expression. [orpha.net]

Prognosis The prognosis for individuals with HSP varies Some individuals are very disabled and others have only mild disability. The majority of individuals with uncomplicated HSP have a normal life expectancy. [brainfacts.org]

Prognosis The prognosis for individuals with HSP varies Some individuals are very disabled and others have only mild disability. [ninds.nih.gov]

Differentiation between HSP and PLS is important for genetic counseling of family members and for the patients' prognosis because HSP generally has a more favorable prognosis than PLS. 1 Furthermore, progression to ALS, as may occur in PLS, 24 is not [jamanetwork.com]

Diagnosis and Prognosis: The diagnosis is usually made by a neurologist. The MRI may show some loss of tissue in certain areas of the brain but this is nondiagnostic. [disorders.eyes.arizona.edu]

Etiology The disease is due to the dysfunction of the upper motor neurons of the corticospinal tract. To date, more than 80 genes have been linked. [orpha.net]

In addition, surgery should also be included as a possible etiology. [symptoma.com]

Etiology .—The disease generally occurs in neurotic families and between the ages of twenty-five and forty, males being more frequently affected. [henriettes-herb.com]

Progressive multiple sclerosis MS is an inflammatory, demyelinating, neurodegenerative disorder of the central nervous system of unknown etiology. Peak age of onset in Primary progressive MS is around 40 years. [explainmedicine.com]

Epidemiology/Etiology The cause of paraplegia due to a spinal cord injury is most often by a car accident. It can also result from a firearm injury, which is not the case in many countries in the world. [physio-pedia.com]

GBA2; 9p13 SPG48: AP5Z1; 7p22 SPG 62: ERLIN1; 10q24 SPG 75: MAG; 19q13 SPG 76: CAPN1; 11q13 SPG 79: UCHL1; 4p13 Spastic Ataxia 1, Hereditary (SPAX1) 21 ● Vesicle-related membrane protein 1 (VAMP1; Synaptobrevin; SYB1) ; Chromosome 12p13.31; Dominant Epidemiology [neuromuscular.wustl.edu]

Consequently, they are often approached together in epidemiological studies. [karger.com]

Summary Epidemiology The prevalence of hereditary spastic paraplegia (HSP) is highly variable, ranging from 1/11,000-77,000 in Europe. Clinical description Clinically, HSPs can be divided into the pure and complex form. [orpha.net]

[…] medical help. en dc.language.iso en dc.relation.ispartofseries Dissertationes medicinae Universitatis Tartuensis;173 dc.subject.other dissertatsioonid et dc.subject.other ETD en dc.subject.other dissertation en dc.subject.other väitekiri et dc.title Epidemiology [dspace.ut.ee]

Epidemiology The global prevalence of HSP is difficult to quantify due to the lack of epidemiological studies of acceptable quality and the difficulty of diagnosing HSP, as it overlaps with other neurological diseases [12]. [physio-pedia.com]

This report highlights the role of ARL6IP1 in the pathophysiology of insensitivity to pain and spastic paraplegia. [ncbi.nlm.nih.gov]

To understand the pathophysiology underlying neurologic deficits in oculodentodigital dysplasia, we studied 8 consecutive patients presenting with hereditary spastic paraplegia due to GJA1 variants. Clinical disease severity was highly variable. [ajnr.org]

These studies illustrate neuropathological similarities between spastic paraplegias and ALS, and highlight the pathophysiological continuum of motor neuron degeneration. [icm-institute.org]

PATHOPHYSIOLOGY 6. Impaired cellular membrane trafficking 7. More particularly axonal transport of macromolecules and organelles. 8. Mutation of proteins, spastin and atlastin-1 causes impaired cellular membrane trafficking. [slideshare.net]

Treatment There are no specific treatments to prevent, slow, or reverse HSP. Symptomatic treatments used for spasticity, such as muscle relaxants, are sometimes helpful. [brainfacts.org]

Stretching Exercises- These exercises are beneficial for increasing range of motion and prevent development of cramps etc. [epainassist.com]

Controls may need to be padded to prevent bruising and scraping if you have spasticity. In addition, a belt around your legs might be considered to prevent contact with controls when experiencing a spasm. [nasdonline.org]

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2. Afshinmajd S, Khalaj A, Roohani Y, et al. Acute paraplegia after general anesthesia. Acta Med Iran. 2011;49(8):560-564.
3. Räty S, Rantanen K, Sundararajan S, Strbian D. Acute chest pain and paraparesis. Stroke. 2015;46(5):e111-113.
4. Sellner J, Luthi N, Schupbach WM, et al. Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings. Spinal Cord. 2009;47:312-317.
5. Gornas MA, Mesallamy AAE, Obeid TH, Babiker AE. An adult male with acute paraplegia. Saudi Med J. 2014;35(10):1285-1287.
6. Bargiela D, Eglon G, Horvath R, Chinnery PF. An under-recognised cause of spastic paraparesis in middle-aged women. Pract Neurol. 2014;14(3):182-184.
7. Qureshi AZ, Adiga S. Adductor tenotomy and selective obturator neurectomy for the treatment of spasticity in a man with paraplegia. J Spinal Cord Med. 2013;36(1):36-39.