1.
Hereditary Spastic Paraplegia
(HSP)

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.
1-10 in 100,000 people worldwide
have HSP
 Can affect people of all ages
, but average age at onset is 24

4.
1
2
3
4
• Hereditary spastic paresis
• Familial spastic paraplegia
• Strumpell-Lorrain disease:
first described 1883-1888
• French Settlement

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.
Complicated HSP
Pure HSP

7.
Based on
mode of
inheritance
Autosomal
dominant
Autosomal
recessive
X-linked
recessive
manner

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.
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.
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.
SPG2
 Mutation in Gene >>>>> Proteolipid protein
1(PLP1)
 Transmembrane protein >>>> leukodystrophy
and dysmyelination, resulting in axonal
degeneration
 Locus = Xq22 X-Linked

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.
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.
SPG17
 Silver syndrome
 Mutation in Gene BSCL2 >>>>> Seipin protein
 Phenotype overlapping with distal spinal
muscular atrophy type VA
 Locus = 11q13 Autosomal dominant

15.
SPG18
 Mutation in Gene >>>>> Erlin-2
 Characterised by joint contractures
and intellectual disability
 Locus = 8p11.23 Autosomalrecessive

16.
Neuropathology
.

17.
Neuropathology cont….

18.
In Neuron Level
Axonal
Degeneration
• Lesser
Extent

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.
Normal reflex during walking Abnormal reflex during Gait/walking

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.
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.
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.
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.
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.
Gen.
Spas
ticity
Oral
Agents
Foc.
Spas
ticity
Reg.
Spas
ticity
Botulinum
Toxins.Ph
enol
Blockade
IntraThecal
Baclofen

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.
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.