Progressive Spastic Paraparesis

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Information about Progressive Spastic Paraparesis

Published on July 3, 2007

Author: NeurologyGuru

Source: slideshare.net

Description

The case of a man who developed progressive gait disturbance and lower limb spasticity

Progressive Spastic Paraparesis AskTheNeurologist.Com Author Anon

R.A 47 year-old man, M + 3, “ farmer”, Moroccan descent 2 ½ - 3 year history of progressive leg weakness

47 year-old man, M + 3, “ farmer”, Moroccan descent

2 ½ - 3 year history of progressive leg weakness

History I Jan 2001:- Tripped and fell and hurt back Suffered LBP radiating down R leg First noticed leg weakness

Jan 2001:-

Tripped and fell and hurt back

Suffered LBP radiating down R leg

First noticed leg weakness

History 2 Over following 2 years 9 months:- Progressive leg stiffness R leg affected predominantly Gait difficulty Frequency of urination…occasionally incontinent

Over following 2 years 9 months:-

Progressive leg stiffness

R leg affected predominantly

Gait difficulty

Frequency of urination…occasionally incontinent

History 3 July 2001:- Hepatosplenomegaly found incidentally Anaemia Myelofibrosis diagnosed (bone marow bx) Treatment commenced ( B12, Folate)

July 2001:-

Hepatosplenomegaly found incidentally

Anaemia

Myelofibrosis diagnosed (bone marow bx)

Treatment commenced ( B12, Folate)

History 4 Denies Arm involvement Speech / visual disturbance Cognitive involvement

Denies

Arm involvement

Speech / visual disturbance

Cognitive involvement

History 5 In childhood normal acquisition of motor-milestones No noticeable problems in walking, running or athletic ability in early life

In childhood normal acquisition of motor-milestones

No noticeable problems in walking, running or athletic ability in early life

Family History Father:- Age 40 began to suffer gait difficulty Over 20 years progressed until bed-ridden with loss of sphincter control Died aged 70 from “ pressure sores” Arms, speech vision, cognition all unaffected at death

Father:-

Age 40 began to suffer gait difficulty

Over 20 years progressed until bed-ridden with loss of sphincter control

Died aged 70 from “ pressure sores”

Arms, speech vision, cognition all unaffected at death

Family History II Sister (aged 47):- Suffered from LBP aged 39 “ discopathy” 1 ½ years ago others noticed gait disturbance 1 year ago RTA…from then on she noticed gait difficulty. Recently urgency of micturition

Sister (aged 47):-

Suffered from LBP aged 39 “ discopathy”

1 ½ years ago others noticed gait disturbance

1 year ago RTA…from then on she noticed gait difficulty.

Recently urgency of micturition

 

Examination Cognitively intact Cranial nerves intact Tone normal in arms, increased in legs Power preserved in arms Right leg 4+/ 5 global Left leg 5/5 Reflexes increased Legs>>arms Ankle and knee clonus bilaterally Babinski bilaterally

Cognitively intact

Cranial nerves intact

Tone normal in arms, increased in legs

Power preserved in arms

Right leg 4+/ 5 global

Left leg 5/5

Reflexes increased Legs>>arms

Ankle and knee clonus bilaterally

Babinski bilaterally

Decreased vibration sense in legs Sensory level mid-lower thoracic Romberg mildly positive No cerebellar signs Gait spastic Examination II

Decreased vibration sense in legs

Sensory level mid-lower thoracic

Romberg mildly positive

No cerebellar signs

Gait spastic

Investigations I CBC - normal Biochem - normal B12 - 596 (normal) LP : - TP 368 - PMN 1 , LYM 0, RBC 1 - OCB -ve

CBC - normal

Biochem - normal

B12 - 596 (normal)

LP : - TP 368

- PMN 1 , LYM 0, RBC 1

- OCB -ve

Immunology: ANA ANCA Anti Ro / La Anti-cardiolipin antibodies Immune electrophoresis ALL NEGATIVE Investigations II

Immunology:

ANA

ANCA

Anti Ro / La

Anti-cardiolipin antibodies

Immune electrophoresis

ALL NEGATIVE

Infective: HIV -ve HTLV-1 pending VDRL pending Investigations III

Infective:

HIV -ve

HTLV-1 pending

VDRL pending

Imaging Previous MRI of cervical, thoracic and lumbar – sacral cord all normal Repeat thoracic MRI normal Investigations IV

Imaging

Previous MRI of cervical, thoracic and lumbar – sacral cord all normal

Repeat thoracic MRI normal

DD Infective : - HTLV – 1 - HIV - Syphilis Inflammatory - MS ( primary progressive) Compressive - spondylosis - neoplastic Metabolic - B12 deficiency Toxic - Lathyrism Hereditary - Hereditary spastic paraparesis Degenerative - Primary lateral sclerosis

Infective : - HTLV – 1

- HIV

- Syphilis

Inflammatory - MS ( primary progressive)

Compressive - spondylosis

- neoplastic

Metabolic - B12 deficiency

Toxic - Lathyrism

Hereditary - Hereditary spastic paraparesis

Degenerative - Primary lateral sclerosis

 

 

 

 

 

Stained with Luxol fast blue – stains myelinated axons

A L A L

Usually lose ability to walk by age 60-70 Usually ambulant until death from other cause More prominent weakness, sensory loss and urinary symptoms Weakness, Sensory loss and urinary symptoms less marked More rapidly evolving course Slower course Onset after 35 years Onset before 35 years TYPE II TYPE I

 

 

 

 

 

 

HSP caused by impaired development of the corticospinal tract

 

PLP mutation PLP ( proteolipid protein) is one of major protein components of CNS myelin A mutation at same locus is responsible for disease “ Pelizaeus-Merbacher” disease ( severe disease due to hypomyelination of CNS)

PLP ( proteolipid protein) is one of major protein components of CNS myelin

A mutation at same locus is responsible for disease “ Pelizaeus-Merbacher” disease ( severe disease due to hypomyelination of CNS)

 

Paraplegin Codes for type of metalloprotease known as AAA metalloprotease. Shown ( via immunofluorescence) to localise to within mitochondia. Muscle biopsies of affected patients show evidence of mitochondrial dysfunction: - e.g. Ragged – red fibres, cytochrome – oxidase negative fibres

Codes for type of metalloprotease known as AAA metalloprotease.

Shown ( via immunofluorescence) to localise to within mitochondia.

Muscle biopsies of affected patients show evidence of mitochondrial dysfunction:

- e.g. Ragged – red fibres, cytochrome – oxidase negative fibres

Severity of muscle findings correlates with severity of HSP! Relevance of muscle changes unclear Paraplegin II

Severity of muscle findings correlates with severity of HSP!

Relevance of muscle changes unclear

AAA metalloproteases are invloved in “ chaperone-like” activity as well as other intracellular functions Can participate in protein quality-control via binding to aberrantly-folded peptides and directing them towards proteolysis. Paraplegin III

AAA metalloproteases are invloved in “ chaperone-like” activity as well as other intracellular functions

Can participate in protein quality-control via binding to aberrantly-folded peptides and directing them towards proteolysis.

? accumulation of aberrant peptides within the mitochondria results in mitochondrial dysfunction Ultimately results in energy deficit for cell Fits-in well with late age of onset Ubiquitous expression of paraplegin…..selective dysfunction may reflect high metabolic demand Paraplegin II

? accumulation of aberrant peptides within the mitochondria results in mitochondrial dysfunction

Ultimately results in energy deficit for cell

Fits-in well with late age of onset

Ubiquitous expression of paraplegin…..selective dysfunction may reflect high metabolic demand

 

Treatment options Antispasticity drugs ( e.g baclofen) Regular physiotherapy Botox injections Minor surgical procedures

Antispasticity drugs ( e.g baclofen)

Regular physiotherapy

Botox injections

Minor surgical procedures

Follow-Up A novel mutation in the SPG4 (spastin) gene was subsequently isolated in this family

A novel mutation in the SPG4 (spastin) gene was subsequently isolated in this family

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