Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by the progressive stiffening and weakening of the lower limbs. The most common symptoms are difficulty walking and lifting the toes. HSP results from degeneration of nerve fibers in the spinal cord that control the lower body, and can be caused by mutations affecting axonal transport, mitochondria, or myelin. While there is no cure, treatment focuses on physical therapy, medication to reduce spasticity and pain, and addressing complications like contractures.

1. HEREDITARY SPASTIC PARAPLEGIADr.Y.Sasikumar

2. Hereditary spastic paraplegia (HSP) is a large group of inherited neurologic disorders, in which the prominent feature is a progressive spastic paraparesis.

3. Dr. Str ü mpell first described hereditary forms of spastic paraplegia in 1883.HSP is group of genetic disorders , the modes of inheritance: autosomal dominant, autosomal recessive, Mitochondrial inheritance and x-linked recessive.Hereditary spastic paraplegia (HSP) is also called familial spastic paraparesis .

4. In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population.. HSP may occur at any age, from infancy through late adulthood (eg, 85 y). Most patients experience the onset of symptoms between the second and fourth decades of life.

5. Degeneration of the ends of the corticospinal tracts within the spinal cord.The ends of the longest fibers, which supply the lower extremities, are affected to a much greater extent than are the fibers to the upper body. Most people with HSP do not have symptoms in the hands or arms. 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.Mitochondrial dysfunction

9. Paraplegin , an ATP-dependent proteolytic complex located at the mitochondrial inner membrane, which controls protein quality and regulates ribosome assembly.

10. Mutation causes mitochondrial dysfunction.Mutation of myelin protein gene Patients with this form of HSP generally show evidence of myelin abnormalities, which are known to affect axon function.

11. CLASSIFICATIONHereditary Spastic Paraplegias are classifiedBased on the symptoms (pure form versus complicated form); Based on their mode of inheritance (autosomal dominant, autosomal recessive or x-linked)Based on the patient’s age at onset.

12. Based on symptoms

13. Spasticity in the lower limbs alone is described as pure HSP.

14. Complicated HSP, additional symptoms may include peripheral neuropathy, epilepsy, ataxia, optic neuropathy, retinopathy, dementia, ichthyosis, mental retardation, deafness, and problems with speech, swallowing.

15. Complicated HSP is rare.Based on patient's age at onset

16. Type I is characterized by age onset below 35 years. Spasticity of the lower limbs is more marked than weakness.Type II is characterized by onset over 35 years.Muscle weakness, urinary symptoms and sensory loss are more marked

17. Based on mode of inheritanceThere are four different modes of inheritance: autosomal dominant

18. autosomal recessive

19. Mitochondrial inheritance

20. x-linked recessive.Autosomal dominant represents the most common mode of inheritance

21. To date, the locations of several genes have been identified by Genetic mapping .

22. 18 types of dominantly inherited pure or complicated HSP are known.

23. 17 types of recessively inherited HSP.

24. 3 types of X-linked HSP.

26. SymptomsThe classic symptom of HSP is progressive difficulty in walking.

27. Patients usually have difficulty lifting their toes; as a result, they drag their toes when walking.

28. In later stages, patients experience difficulty flexing the thigh muscle when walking.

29. Experience increased muscle tone. Some patients complain of reduced sensation in the distal regions of the legs.

30. Some people also experience urinary problems (eg, incontinence)

31. Some patients eventually may require the use of a wheelchair.Abnormal gaitIncreasing stiffness in the legs is associated with frequent tripping.

32. Uncontrollable shaking of the legs may be noted when the patient ambulates.

33. Dragging of the feet, scissoring of the legs during ambulation. Decreased sense of balanceA common symptom of HSP is a decreased sense of balance.

34. For many people, this is the first symptom. Epilepsy, ataxia, optic neuropathy, retinopathy, dementia, ichthyosis, mental retardation, deafness, and problems with speech, swallowing. Physical SignsUpper extremity muscle tone and strength are normal.

35. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps, and ankles.

36. Weakness is most notable at the iliopsoas muscles, the tibialis anterior muscles, and, to a lesser extent, the hamstring muscles. Muscle wasting may occur in patients with pure HSP.

37. It is mild and is limited to atrophy of the shins in elderly & wheelchair-dependent patients.Peripheral nerves are normal in patients with pure HSP.

38. Vibratory sensation is often mildly diminished in the distal lower extremities.

39. Deep tendon reflexes are pathologically increased (3+ to 4+) in the lower extremities. The patient's gait demonstrates circumductionowing to a difficulty with hip flexion and ankle dorsiflexion.

40. Ankle clonus, and extensor plantar responses are uniformly present.

41. Hoffman sign may be observed.

42. High-arched feet (pescavus) are generally present and are usually prominent in older patients.workupGenetic Testing