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Hereditary spastic paraplegia


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Hereditary spastic paraplegia

  1. 1. Hereditary Spastic Paraplegia (HSP)
  2. 2. Definition: is a group of inherited diseases whose main feature is progressive stiffness and contraction (spasticity) in the lower limbs , as a result of damage to or dysfunction of the nerves.
  3. 3. 1-10 in 100,000 people worldwide have HSP  Can affect people of all ages , but average age at onset is 24
  4. 4. 1 2 3 4 • Hereditary spastic paresis • Familial spastic paraplegia • Strumpell-Lorrain disease: first described 1883-1888 • French Settlement
  5. 5. Based on symptoms Pure HSP    Affects the legs only More common Bladder symptoms may occur eg “urgency” Complicated HSP  Spastic paraplegia with a variety of other problems  Other neurological problems eg ataxia (poor balance) Intellectual disability , dementia, extrapyramidal signs,Seizures
  6. 6. Complicated HSP Pure HSP
  7. 7. Based on mode of inheritance Autosomal dominant Autosomal recessive X-linked recessive manner
  8. 8. Based on patient's age at onset Type I <35 years Type II >35 years Spasticity>>weakness muscle weakness urinary symptoms sensory loss spasticity
  9. 9. Based on associated gene (Genetics)  Neuronal degeneration mutations at specific genes  Genetic mapping has identified at least 52 different HSP loci, designated SPG 1 through 52  Different genetic types of HSP usually cannot be distinguished by clinical and neuroimaging parameters alone
  10. 10. SPG1 (Spastic Paraplegia 1)  Masa syndrome Gareis-Mason syndrome Crash syndrome  Mutation in Gene >>>>> L1 or L1CAM protein  Transmembrane protein >>>> neurite outgrowth guidance, neuronal cell migration and survival  Locus = Xq28 X-Linked
  11. 11. SPG2  Mutation in Gene >>>>> Proteolipid protein 1(PLP1)  Transmembrane protein >>>> leukodystrophy and dysmyelination, resulting in axonal degeneration  Locus = Xq22 X-Linked
  12. 12. SPG4  Mutation in Gene SPAST >>>>> Spastin protein  Microtubule-severing protein >>> membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis  Locus = 2p22–p21 Autosomal dominant
  13. 13. SPG15  Kjellin syndrome  Mutation in Gene >>>>> ZFYVE26  progressive stiffness and increased reflexes in the leg muscles as well as retinal degeneration  Locus =14q24.1 Autosomal recessive
  14. 14. SPG17  Silver syndrome  Mutation in Gene BSCL2 >>>>> Seipin protein  Phenotype overlapping with distal spinal muscular atrophy type VA  Locus = 11q13 Autosomal dominant
  15. 15. SPG18  Mutation in Gene >>>>> Erlin-2  Characterised by joint contractures and intellectual disability  Locus = 8p11.23 Autosomalrecessive
  16. 16. Neuropathology .
  17. 17. Neuropathology cont….
  18. 18. In Neuron Level Axonal Degeneration • Lesser Extent
  19. 19. Clinical Features  Symptoms depend on the type of HSP inherited  Main feature >>> progressive spasticity in the lower limbs, due to pyramidal tract dysfunction  In the lower extremities, spasticity is increased at the hamstrings, quadriceps and ankles  Weakness is most notable at the iliopsoas , tibialis anterior, hamstring muscles  difficulty in walking, decreased vibratory sense at the ankles, and paresthesia  In lower extremities hyperreflexia, brisk reflexes, extensor plantar reflexes
  20. 20. Normal reflex during walking Abnormal reflex during Gait/walking
  21. 21.  additional symptoms in complicated form include: peripheral neuropathy, amyotrophy, ata xia, mentalretardation, ichthyosis, epile psy,optic neuropathy, dementia, deafne ss, or problems with speech, swallowing or breathing
  22. 22. Diagnosis Genetic Instrumental testing Tests Examination leg muscles Brain and spine MRI Family feel stiff Rule out other history causes brisk reflexes any History relatives Complains affected? eg .walking difficulty
  23. 23. Genetic testing • Diagnostic - Person is affected with symptoms - Wants to know the cause • Predictive - Person not affected with symptoms - Has a relative eg parent with HSP
  24. 24. Differential Diagnosis • • • • • • • Childhood onset Diplegic cerebral palsy Structural (Chiari malformation, atlanto-axial subluxation) Leucodystrophy (eg, Krabbe’s) Metabolic (arginase defi ciency, abetalipoproteinaemia) Levodopa-responsive dystonia Infection (myelitis) Multiple sclerosis • • • • • • • • • • • • • • • Adult onset Cervical spine degenerative disease Multiple sclerosis Motor neuron disease Neoplasm (primary/secondary spinal tumour, parasagittal meningioma) Infection (myelitis) Dural arteriovenous malformation Chiari malformation Adrenoleucodystrophy Hereditary spastic paraplegia Spinocerebellar ataxias Vitamin defi ciency (B12 and E) Lathyrism Levodopa-responsive dystonia Infection (syphilis, human T-cell leukaemia virus 1, HIV) Copper deficiency
  25. 25. Treatment No specific treatment is known that would prevent, slow, or reverse HSP Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being
  26. 26. Gen. Spas ticity Oral Agents Foc. Spas ticity Reg. Spas ticity Botulinum Toxins.Ph enol Blockade IntraThecal Baclofen
  27. 27. • Baclofen– a voluntary muscle relaxant to relax muscles and reduce tone • Tizanidine – to treat nocturnal or intermittent spasms • Diazepam and Clonazepam – to decrease intensity of spasms • Oxybutynin chloride– an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems • Tolterodine tartate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems • Botulinu toxin – to reduce muscle overactivity • Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression
  28. 28. Physical Therapy  To restore and maintain the ability to move  To reduce muscle tone  To maintain or improve range of motion and mobility  To increase strength and coordination  To prevent complications, such as frozen joints, contractures, or bedsores.