Myogenic palsies

Question 1

what are examples of myogenic palsies

Answer 1

chronic progressive external ophthalmoplegia (cpeo)
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
the weakness of ocular movement is due to a primary problem affecting the muscle itself rather than one disrupting the nerve supply or causing mechanical restriction

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

Question 6

mtDNA and CPEO+

Answer 6

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 8

Karens Sayre syndrome

Answer 8

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 9

MRI study in CPEO

Answer 9

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 10

EOMs affected in CPEO

Answer 10

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

Question 11

what is found for both neurogenic and myogenic palsies

Answer 11

A
degeneration of brainstem

increased latency of blink response

restriction of voluntary eye movements

abnormal mri

muscle co contraction

Question 12

what is a common MRI finding for both cpeo and cpeo+

Answer 12

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

Question 13

what structures are affected in cpeo +

Answer 13

muscle and peripheral nerves

Question 14

what are the differential diagnosis for cpeo

Answer 14

cfeom - congenital fibrosis for the eom

myasthenia gravis

3rd nerve palsy

graves rbitopathy

oclopharangeal dystrophy

Question 15

what is ocularpharanogeal dystrophy

Answer 15

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 16

what is necessary for the differential diagnosis of cpeo

Answer 16

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 17

is muscle biopsy conclusive evidence for the presence of cpeo

Answer 17

A
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 18

how is cpeo managed

Answer 18

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

Referral to…
Neurologist, Cardiologist – (ECG important to rule out cardiac abnormalities), Audiologist, Dysphagia (difficulty swallowing) – refer to appropriate specialist, Endocrinologist

Question 19

How to treat symptoms of CPEO

Answer 19

Symptoms
Transient/ constant diplopia appreciated by 28%- 63%
Prisms
Occlusion
Ptosis
Horizontal strabismus exo more common

Treatment
Ptosis props – glasses / haptic contact lenses with shelf
Tape
Surgery
EOM / lids (Potential anaesthetic risks = LA; heart block/pharyngeal muscle weakness)

Question 20

what eom surgery is done for people with

Answer 20

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 21

what are the associated cognitive disorders associated with cpeo

Answer 21

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 22

how many people does myotonic dystrophy affect and what does it cause

Answer 22

Affects 1/8000

Inability of muscle to relax after contraction
Typically affects the muscles of mastication, hand and forearm, tongue, shoulders, legs

Question 23

what are the ocular features of myotonic dystrophy

Answer 23

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 24

what are the general features of myotonic dystrophy

Answer 24

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

Question 25

what is ocular myositis

Answer 25

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 26

ocular symptoms of ocular myositis

Answer 26

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 27

how do the muscles change in eom

Answer 27

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 27

what are the differential diagnosis for ocular myositis

Answer 27

GO
Idiopathic orbital pseudo-tumour
Orbital cellulitis
Orbital rhabdomyosarcoma

Question 28

what are the management options for orbital myositis

Answer 28

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 29

what is a orbital pseudo
tumour/ idiopathic orbital inflammatory disease

Answer 29

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 30

what are the ocular characteristics of orbital pseduotumour

Answer 30

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

what is ocular myositis is a subgroup of

A
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

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

IIH is a pseudotumour cerebri

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 rhabdomyosarcoma present with

aggressive childhood cancer

Answer 37

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

A
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