hereditary spastic paraplegia defenition

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. Hereditary Spastic Paraplegias are classified
1. Based on the symptoms (pure form versus
complicated form);
2. Based on their mode of inheritance
(autosomal dominant, autosomal
recessive or x-linked)
3
. Based on the patient’s age at onset.

6.  Based on symptoms
 Spasticity in the lower limbs alone is
described as pure HSP.
 Complicated HSP, additional symptoms may
include peripheral neuropathy, epilepsy,
ataxia, optic neuropathy, retinopathy,
dementia, ichthyosis, mental retardation,
deafness, and problems with speech,
swallowing.
 Complicated HSP is rare.

7.  Based on patient's age at onset
 Type Iis characterized by age onset below 35
years.
Spasticity of the lower limbs is more marked
than weakness.
 Type IIis characterized by onset over 35
years.
Muscle weakness, urinary symptoms and
sensory loss are more marked

8.  Based on mode of inheritance
There are four different modes of inheritance:
 autosomal dominant
 autosomal recessive
 Mitochondrial inheritance
 x-linked recessive.
Autosomal dominant represents the most
common mode of inheritance

9. o To date, the locations of several genes have
been identified by Genetic mapping .
o 18 types of dominantly inherited pure or
complicated HSP are known.
o 17 types of recessively inherited HSP.
o 3 types of X-linked HSP.

10. Type Gene Locus Description
Autosomal
dominant
SPG4
(spastinprotein)
2p22-p21 Disturbances in
axonal cytoskele
ton
Autosomal
dominant
SPG3A
(atlastin protein)
14q11-q21 Abnormal
synaptic
structure and
impaired neurot
ransmission,
Also known as
Strumpell
disease.
Autosomal
dominant
SPG10
(KIF5Aprotein)
12q13 associated with
distal muscle
atrophy.
Autosomal
recessive HSP
SPG7 16q24.3 mitochondrial
malfunction in
neurons,
leading to
axonal
degeneration

11. Type
Gene Locus Description
Autosomal
recessive HSP
SPG20 13q12.3 Distal muscle
wasting
X-Linked SPG2 xq22 Mutations in
the proteolipid
protein cause
progressive leuk
odystrophy and
dysmyelination,
resulting in
axonal
degeneration.[29
X-Linked SPG1 11q13 interfere with
neuronal cell
migration and
neuronal cell
survival, causing
reduced
corticospinal
tracts.

12. Symptoms
o The classic symptom of HSP is progressive
difficulty in walking.
o Patients usually have difficulty lifting their
toes; as a result, they drag their toes when
walking.
o In later stages, patients experience difficulty
flexing the thigh muscle when walking.
o Experience increased muscle tone.

13. o Some patients complain of reduced sensation
in the distal regions of the legs.
o Some people also experience urinary
problems (eg, incontinence)
o Some patients eventually may require the use
of a wheelchair.

14. Abnormal gait
o Increasing stiffness in the legs is associated
with frequent tripping.
o Uncontrollable shaking of the legs may be
noted when the patient ambulates.
o Dragging of the feet, scissoring of the legs
during ambulation.

15. Decreased sense of balance
o A common symptom of HSP is a decreased
sense of balance.
o For many people, this is the first symptom.

16. o Epilepsy, ataxia, optic
neuropathy, retinopathy, dementia, ichthyosis
, mental retardation, deafness, and problems
with speech, swallowing.

17. Physical Signs
o Upper extremity muscle tone and strength
are normal.
o In the lower extremities, muscle tone is
increased at the hamstrings, quadriceps, and
ankles.
o Weakness is most notable at the iliopsoas
muscles, the tibialis anterior muscles, and, to
a lesser extent, the hamstring muscles.

18. o Muscle wasting may occur in patients with
pure HSP.
o It is mild and is limited to atrophy of the
shins in elderly & wheelchair-dependent
patients.

19. o Peripheral nerves are normal in patients with
pure HSP.
o Vibratory sensation is often mildly diminished
in the distal lower extremities.
o Deep tendon reflexes are pathologically
increased (3+ to 4+) in the lower extremities.

20. o The patient's gait demonstrates
circumduction owing to a difficulty with hip
flexion and ankle dorsiflexion.
o Ankle clonus, and extensor plantar responses
are uniformly present.
o Hoffman sign may be observed.
o High-arched feet (pes cavus) are generally
present and are usually prominent in older
patients.

21.  Genetic Testing
 Imaging Studies
MRI scans may demonstrate atrophy of the spinal
cord.
Cortical evoked potentials –(used to measure
neurotransmission in corticospinal tracts)
show reduced conduction velocity and reduced
amplitude of the evoked potential in the
corticospinal tract .
 Lower extremity somatosensory evoked
potentials -show a conduction delay in dorsal
column fibers.

22. ⦁ Cortical evoked potentials of the arms are
usually normal.
⦁ CSF -Usually normal,some may show
increased protein level.

23.  Autopsy studies of autosomal dominant HSP
have demonstrated axonal degeneration of
the long descending tracts(ventral and lateral
corticospinal tracts).
 Degeneration was maximal in the distal
axons of these fibers.

24.  Spinocerebellar fibers are involved to a lesser
extent.
 Neuronal cell bodies of degenerating fibers
are preserved.
 Loss of anterior horn cells is observed in
some cases.

25. Currently, no specific treatment exists to
prevent, retard, or reverse progressive
disability in patients with HSP.
Rehabilitation programme
o Regular physical therapy (PT) is important for
maintaining and improving range of motion
(ROM) and muscle strength.
o PT does not reduce the degenerative process
within the spinal cord.

26. The exercise programs include strengthening,
stretching, and aerobic exercises.
 Strengthening exercises - These help to
strengthen muscles & decreasing the rate of
functional impairment.
o Exercise may also help to slow the
development of disuse atrophy.
o Back-strengthening exercises may help to
reduce or eliminate back pain (due poor gait,
poor posture, use of a mobility device).

27.  Stretching exercises –
These help to maintain or increase ROM and to
reduce muscle cramps.
 Aerobic exercises –
o These improve cardiovascular fitness, reduce
fatigue, and increase endurance and general
fitness.
o Walking, bicycle riding, water aerobics, and
swimming

28. Exercise also has a positive psychological
effect, helping to reduce stress and produce
feelings of well-being.

29. Medication
⦁ The goals of pharmacotherapy are to reduce
morbidity and prevent complications.
Antispasmotic drugs
Eg-Oxybutynin
o Inhibits the action of acetylcholine on smooth
muscle
o Causes an increase in bladder capacity and a
decrease in uninhibited contractions.

30. SKELETAL MUSCLE RELAXANT
Baclofen
o Induce the hyperpolarization of afferent
terminals and inhibit monosynaptic and
polysynaptic reflexes at the spinal level.
Tizanidine
o Centrally acting muscle relaxant.

31. Dantroline sodium
o Stimulates muscle relaxation by modulating
skeletal muscle contractions at the site
beyond the myoneural junction.
Botilinum toxin
o Binds to receptor sites on motor nerve
terminals and inhibits the release of
acetylcholine, which in turn inhibits the
transmission of impulses in neuromuscular
tissue.
o This agent is most useful for treating
spasticity in the gastrocnemius and soleus
muscles.

32. Benzodiazepines
Diazepam (Valium)
o Depresses all levels of CNS, possibly by
increasing the activity of GABA.

33. Gastrocnemius-soleus contracture:
o This condition is more common when
symptoms begin in childhood rather than in
adulthood.
Cold feet:
o Many people with HSP complain of cold feet.
o Cold feet may be related to abnormal
thermoregulation of cutaneous vessels;
however, circulation is usually preserved.

34. Fatigue:
o The extra effort required for walking, because
of muscle weakness in the legs.
o Various medications prescribed for HSP
cause drowsiness & fatigue.
o 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

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