myogenic palsies

Question 1

what are examples of myogenic palsies

Answer 1

chronic progressive external ophthalmoplegia

cleo, cpeo+ , myotonic dystrophy

ocular myositis

tumours of muscle e.g. rhabdomyoscarm

Question 2

define myogenic palsy

Answer 2

a primary disease of a muscle causing it to underact

Question 3

what is cpeo

Answer 3

chronic progressive external ophthalmoplegia

progressive bilateral ptosis usually procecing motility loss

progressive symmetrical loss of motility

eyes become virtually immobile

obicularis weakness

bells phenomena often affected

fibrotic changes may occur later

Question 4

aetiology of cpeo

Answer 4

mitchondrial ocular disorders

deletion of mitochondrial dna

age of onset - early 2os

genetics

sporadic but autosomonal dominant form does occur

the ocular characteristics develop - isolation cpeo

association with multi system defects = cpeo+

Question 5

what is cpeo+

Answer 5

opthalmoloplegi +

retinal pigmentary changes (retinitis pigmentosa)
cardiac defects
deafness (cochlear epithelium metabolically active tissue)
cerebellar ataxia
peripheral neuropathy
impaired cognition (mental retardation)
endocrine dysfunction
reduced grey matter and cerebellar volumes

Higher levels of deleted mtDNA in a wider range of tissue
Multiple mtDNA deletions in skeletal muscle, which are 2° to a nuclear genetic defect affecting mtDNA maintenance, replication or repair

Question 6

what is Kearns Sayre syndrome

Answer 6

Onset - by age 20 (typically present in childhood)
Ocular
Ophthalmoplegia
Bilateral ptosis
Orbicularis weakness
Bell’s phenomenon affected & difficulty closing lids
Retinal pigmentary changes
General (Higher levels of deleted mtDNA in a wider range of tissues)
Heart block - cardiac conduction defects
Cerebellar ataxia
High cerebrospinal fluid

Question 7

why are the eom’s affected in cpeo

Answer 7

it is a mitochondria disorder

• deletion of the different lengths of mtdna defective mitochondrial function

eom have a higher mitochondrial volume than other Skelton volume

Mitochondrial DNA encodes for essential components of the respiratory chain. Deletions of various lengths of mtDNA results in defective mitochondrial function, particularly in highly oxidative tissues (eg, muscle, brain, heart). Extraocular muscles are affected preferentially because their fraction of mitochondrial volume is several times greater than that of other skeletal muscle.[5,6] and therefore affected

MRI study
A significant reduction in EOM volume in the CPEO group compared to normal for all 4 recti muscles. Approx 10 in each group
Reduction ranged between 24-40%
There was a significant reduction in extraocular muscle volumes in the CPEO group compared with normal controls for all four recti muscles , ranging from 24.7% to 40.2% ( Figure 2).
= EOM atrophy (Myogenic palsy)

Question 8

what is found for both neurogenic and myogenic palsies

Answer 8

degeneration of brainstem

increased latency of blink response

restriction of voluntary eye movements

abnormal mri

muscle co contraction

Question 9

what is a common finding for both cpeo and cpeo+

Answer 9

significant reduction in grey matter and cerebellar volumes for both types of cpeo patients q

Question 10

what structures are affected in cpeo +

Answer 10

muscle but also peripheral nerves and affected in cpeo+

Question 11

what are the differential diagnosis for cpeo

Answer 11

cfeom - congenital fibrosis for the eom

myasthenia gravis

3rd nerve palsy

graves rbitopathy

oclopharangeal dystrophy

Question 12

what is ocularpharanogeal dystrophy

Answer 12

Inheritance: autosomal dominant
Aetiology: caused by short triplet repeat expansion
Characteristics
Onset - 5th decade of life
Pharangeal weakness - difficulty swallowing
Facial and limb weakness
Pain in proximal muscles
Ocular (mimics CPEO)
Progressive bilateral ptosis
OM, orbicularis and Bells Phenomenon usually intact – may develop limitation of elevation later
Saccades - reduced

Question 13

what is necessary for the differential diagnosis of cpeo

Answer 13

Onset
Natural history
Saccadic velocities ↓
CT / MRI - atrophic muscles
Muscle biopsy - (skeletal muscle/ eye muscle)
Histology for ‘ragged red fibres’
Genetic testing for mtDNA deletions

Question 14

is muscle biopsy conclusive evidence for the presence of cpeo

Answer 14

Muscle biopsy provides important clues to the diagnosis of patients presenting with CPEO.

However, in about 40% of patients, histological studies may not be diagnostic of mitochondrial myopathy.

Histological studies should be combined with genetic studies for the definitive diagnosis of CPEO syndrome.

Question 15

how is cpeo managed

Answer 15

Nutritional supplements explored to increase mitochondrial function
Currently no effective evidence-based disease modifying therapy identified (Pfeffer and Chinnery 2013)
Gene therapy
no cases treated with this as yet
Full investigation – may involve
Neurologist
Cardiologist – ECG important to rule out cardiac abnormalities
Audiologist
Dysphagia (difficulty swallowing) – refer to appropriate specialist
Endocrinologist

Question 16

how would ocular symoptins and signs of cpeo be treated

Answer 16

Treatment of ocular signs and symptoms
Transient/ constant diplopia appreciated by 28%- 63%
Prisms
Occlusion
Ptosis
Ptosis props – glasses / haptic contact lenses with shelf
Tape
Surgery
EOM / lids (Potential anaesthetic risks = LA; heart block/pharyngeal muscle weakness)

The strabismus is typically horizontal (exo more common than esotropia)

Question 17

what eom surgery is done for people with cpeo

Answer 17

Stanworth 1963 bimedial resections
Tarkinen 1965 resections
Sorkin 1997 resections more effective
larger resections required
adjustable sutures not effective
Wallace 1997 recessions due to restrictive nature

Bilateral LR recess (17mm)/ MR resect (7mm)

Question 18

what are the associated cognitive disorders associated with cpeo

Answer 18

Impaired mitochondrial energy production result in dysfunction of all energy-dependent cell functions.

Cognitive decline
Nil detectable - to acute confusional state and disorientation
May develop memory deficits

Question 19

what is myotonic dystrophy

Answer 19

Hereditary disorder of muscle fibre membrane
Inheritance: autosomal dominant
Caused by triplet repeat expansion in the dystrophia myotonica protein kinase (DMPK) gene
Affects 1/8000
Inability of muscle to relax after contraction
Typically affects
muscle of mastication
muscles of the hand and forearm
Tongue
Shoulders
legs

Question 20

what are the ocular features of myotonic dystrophy

Answer 20

Ocular
Symmetrical ophthalmoplegia
Sluggish miotic pupils
Bilateral ptosis
Retinal changes - pigmentry retinopathy
Cataract – e.g. ‘snowflake cataract’
Meibomian gland dysfunction - epihoria

Biopsy of skeletal or ocular muscles show an increased number of nuclei, often shrunken but sometimes enlarged

In advanced stages muscle fibres are replaced by connective tissue and fat cells

Question 21

what are the general features of myotonic dystrophy

Answer 21

General
Facial weakness
Sagging jaw, thin neck
General weakness
Baldness
Cardiac conduction defect (90%)

Question 22

what are the general features of myotonic dystrophy

Answer 22

General
Facial weakness
Sagging jaw, thin neck
General weakness
Baldness
Cardiac conduction defect (90%)

Question 23

what is ocular myositis

Answer 23

Inflammatory process involving one or more EOM
Subgroup of idiopathic orbital inflammatory syndromes (IOIS)
Aetiology: Often following respiratory tract infection - ? autoimmune response
Reported following strabismus surgery
Wolf et al (2007). JAAPOS 11:373-376
Majority present between 18 – 40 years (range 9 – 84)
Approx 2:1 F:M

Question 24

ocular symptoms of ocular myositis

Answer 24

Acute onset / may be recurrent
Unilateral (typical) - bilateral cases reported (rare)
Painful ophthalmoplegia and signs of inflammation
Proptosis
Ptosis
Diplopia – Affects horizontal muscle more than vertical MR>LR, SR>IR
Self limiting - 4-8 weeks, responds well to steroids

Up to 50% do not c/o pain!
Affect horizontal recti first followed by vertical recti

Question 25

how do the muscles change in eom

Answer 25

First 10 days EOM function normal

11-14 days paretic phase

17-24 days restrictive / mixed phase – resolve / permanent
Siatkowski et al (1994) AJO 118:343-50

Isolated involvement of the levator
Wheatcroft (1999) BJO 83:628

Question 26

what are the differential diagnosis for ocular myositis

Answer 26

GO

Idiopathic orbital pseudo-tumour

Orbital cellulitis

Orbital rhabdomyosarcoma

Question 27

what are the management options for ocular myositis

Answer 27

Orthoptic management
Make comfortable with prisms whilst wait for recovery
Occlusion
May have persistent motility problem, if stable for min 3 months consider surgical treatment treatment
Bessant & Lee (1995):
5 patients with orbital myositis, describe use of Botulinum Toxin, 2 needed surgery later.

Question 28

what is a orbital pseudo tumour / idiopathic orbital inflammatory disease

Answer 28

Is a nonspecific, non-neoplastic inflammatory process of the orbit
Accounts for 8-11% of all orbital tumours
Aetiology: unknown
possibly caused by infection, autoimmune disorder and aberrant wound healing
Acute onset over a period of days / weeks
Onset: any age more likely in adults

Question 29

what are the ocular characteristics of orbital pseduotumour

Answer 29

Ocular characteristics
Proptosis (82%)
Periobital oedema
Mechanical limitation of eye movements (54%)
Pain with and without movement of the eyes
Diplopia
Erythema (redness of skin)
Visual acuity loss (38%)

Question 30

what is ocular myositis is a subgroup of

Answer 30

ocular myositis is a subgroup of orbital pseudotumout

enchacement of orbital fat on ct scan

granulomatous tissue infiltrated with lymphocytes and plasma cells

biopsy may be necessary to differentiate from orbital tumour

risks
if no improvement

Question 31

how are orbital pseduotumours diagnosed

Answer 31

Diagnosis
Often by exclusion
Lab tests normal
Orbital imaging
Biopsy

Question 32

how is orbital pseudo tumour treated

Answer 32

Treatment
Steroids
Orbital decompression
Low dose radiation therapy

Question 33

what is the prognosis for pseduotumour

Answer 33

Prognosis
Long term is favourable
30% recurrence rate

Question 34

what are the types of orbital tumours

Answer 34

Primary tumour of the muscle (rare)
Haemangioma / lymphangioma / neurofibroma / Rhabdomyosarcoma

Secondary tumour - Infiltration of a tumour into EOM from orbit / adjacent sinus / bones
Lymphangioma / ON glioma / lacrimal tumour

Metastases
Commonly from skin / breast cancers

Question 35

what are the characteristics of orbital tumours

Answer 35

Enlargement of muscle
Infiltration of tumour
Muscle weakness & mechanical restriction
? Associated with
Infection / haemorrhage / abscess / cystic lesion

Mass effect within orbit
Space occupying lesion
Mechanical restriction

Question 36

what are orbital rhadbomyarcoma

Answer 36

Fast growing highly malignant tumour of striated muscle

Arise from cells called rhabdomyoblast (primative muscle cell), instead of differentiating to striated muscle grows out of control

Presents in childhood, typically <5 yrs, 70% <10yrs

Head and neck (around eyes) 35-40%, genitourinary tract 20%, extremities 20%, chest/lungs 10-15%

Question 37

what would a child with orbital rhabdomyscarmo present with

Answer 37

child with protoptosis

recent onset diplopia

rapid vision changes

restricted motility

Question 38

what would you find in a case example

Answer 38

Symptoms occurring over previous month
irritation of left eye
watering of left eye
blurred vision for approximately 2 weeks
Signs
LVA 0.14 logMAR
L proptosis 3mm
L RAPD
Restriction of ocular motility

bilateral ptosis
om -2 limitation all direction of both eyes

Question 39

what further investigations are necessary

Answer 39

CT scan of head and orbits
inflammatory mass at the apex of the left orbit
presumed pseudotumour

Thyroid auto-antibodies / TFTs

TFTs include measuring theamount of the thyroid hormones, Thyroxine (T4) or Tri-iodothyronine (T3)and/or the pituitary hormone, Thyroid Stimulating Hormone (TSH) in your blood.

Question 40

what management options would there be for orbital rhabdoscarmo

Answer 40

high dose steroids - presidinoslone - 80mg

proptosis resolved , no restriction of eye movements

steroids reduced gradually over 2months period

failure to reduce steroids - without recurrente in symptoms

referred for second opinion - biopsy

no biopsy due to sudden onset of symptoms over week or months more likely to be due to malignancy

steroid maintenance

low dose radiotherapy to orbit

Question 41

what would you find on histology for someone with cpeo

Answer 41

histopathology demonstrates ragged red fibres

a marker for dysfunction of mitochondrial dna

ragged fibres denote the absence of cytochrome oxidase

Question 42

what is the aetiology of orbital cellulitis

Answer 42

Orbital cellulitis is an infection that involves the soft tissues posterior to the orbital septum, including the fat and muscle within the bony orbit.
It can be associated with severe sight and life-threatening complications and therefore requires prompt diagnosis and initiation of treatment.
Orbital cellulitis can occur at any age but is more common in the paediatric population.
Orbital cellulitis have been classified by Chandler and Maloney. Chandler classified into preseptal versus postseptal and Maloney into 5 categories.
Preseptal tend to occur as a result of insect bites or orbital trauma whereas postseptal usually is a result of acute sinusitis.

Question 43

what are the clinical characteristics off orbital cellulitis

Answer 43

Clinical characteristics include:
Periorbital oedema
Ocular pain
Proptosis
Chemosis
Restricted ocular motility - ophthalmoplegia
Reduced visual acuity
Conservative management options are often preferred over surgery in patients with orbital cellutis.

Question 44

what is the aetiology of orbital tumours

Answer 44

An orbital tumour can be a
Primary tumour of the extraocular muscle (EOM) which is rare. The tumour can be a haemangioma, lymphangioma, neurofibroma or rhabdomyosarcoma.
Secondary tumour caused by infiltration of a tumour into extraocular muscle (EOM) from the orbit, adjacent sinus or bones such as a lymphangioma, haemangioma, optic nerve glioma, lacrimal tumour.
Metastases commonly from skin or breast cancers
The tumour may cause enlargement of extraocular muscle (EOM) resulting in mechanical restriction and weakness. There may be associated infection, haemorrhage, abscess or cystic lesion.

Question 45

how would you diagnose a orbital tumour

Answer 45

To diagnose the type of tumour and extent of the tumour, the investigation involves scans and biopsy. A CT scan will identify the location of the tumour and involvement of orbital bone. MRI scan provides visualisation of soft tissue involvement and the location of the tumourin relation to orbital structures such as the optic nerve and extraocular muscles.
Orbital tumours can result inorbital congestion, vascular occlusion, and optic nerve compression.
Clinical ocular findings may include
Proptosis
Reduced visual acuity and development of amblyopia in young children
Restricted ocular motility and strabismus associated with symptom ofdiplopia
Visual field defect
Choroidal folds
Compressive optic neuropathy