Myogenic Palsies Flashcards
What is a myogenic palsy?
A myogenic palsy is a form of paralytic strabismus in which 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. Primary disease.
What are some types of myogenic palsies?
- Chronic progressive external ophthalmoplegia (CPEO)
- CPEO+
- Myotonic Dystrophy (Ocular myositis/pseudo-tumour, tumours of muscle)
What is involved in Chronic Progressive External Ophthalmoplegia (CPEO)?
CPEO represents a number of conditions that have in common the presence of a progressive external ophthalmoplegia.
-Progressive bilateral ptosis usually preceding motility loss
- Progressive symmetrical loss of motility
Eyes become virtually immobile - Orbicularis weakness
- Bell’s phenomenon often affected (the tendency of the eyes to drift up when we close them
- Fibrotic changes may occur later after the eyes become virtually immobile. Identified in forced duction testing.
- Saccadic velocities are always reduced
- Smooth muscle is not affected and pupillary reactions and accommodation remain normal
Is CPEO normally bilateral or unilateral in ptosis?
Progressive bilateral ptosis
Is loss of motility in CPEO symmetrical or asymmetrical?
Symmetrical
What can forced duction testing identify in CPEO?
Fibrotic changes may occur later after the eyes become virtually immobile.
What velocities are always reduced in CPEO?
Saccadic velocities
What remains unaffected and normal in CPEO?
Smooth muscle is not affected and pupillary reactions and accommodation remain normal
What does CPEO stand for?
Chronic Progressive External Ophthalmoplegia
What is CPEO caused by?
Mitochondrial ocular disorder with deletion of mitochondrial DNA (mtDNA).
Genetically it’s sporadic but autosomal dominant form does occur
What is the age of onset in CPEO?
Early 20’s but infancy to 70 years has been reported
What is CPEO and CPEO+?
CPEO = Isolation
CPEO+ = Association with multisystem deficits
What is CPEO+? What symptoms are included?
Ophthalmoplegia Plus
- retinal pigmentary changes (retinitis pigmentosa) – a.k.a. salt and pepper changes
- cardiac defects
- deafness (cochlear epithelium metabolically active tissue)
- cerebellar ataxia
- peripheral neuropathy
- impaired cognition
- endocrine dysfunction
- reduced grey matter and cerebellar volumes
What does it mean if someone has higher levels of deleted mtDNA in CPEO?
Wider range of tissues affected. Secondary to nuclear genetic defect affecting mtDNA (mitochondrial DNA)maintenance, replication or repair
What is CPEO+ also known as?
Kearns Sayre Syndrome
What is Kearns-Sayre Syndrome also known as?
CPEO
What age is Kearns-Sayre Syndrome usually diagnosed?
By age 20 (typically presents in childhood)
What ocular syndromes are present in Kearns-Sayre Syndrome?
- Ophthalmoplegia
- Bilateral ptosis
- Orbicularis weakness
- Bell’s phenomenon affected & difficulty closing lids
- Retinal pigmentary changes (salt and pepper retinopathy, RPE changes prominent in macula, periparillary retina and equatorial region)
What general syndromes (non-ocular) are present in Kearns-Sayre Syndrome?
- Heart block - cardiac conduction defects (heart rhythm disturbance where the hearts electrical impulses are conducted very slowly)
- Cerebellar ataxia
- High cerebrospinal fluid
What are the extraocular muscles affected in CPEO?
Deletion of different length of mtDNA → defective mitochondrial function
EOMs have higher mitochondrial volume than other skeletal muscles
Inherited from mother
What did Yu-Wai-Man et al (2013) find out about CPEO and EOMs?
MRI revealed EOM atrophy (myogenic palsy) in CPEO
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%
What is EOM atrophy like in CPEO?
The EOM atrophy is symmetrical as the right and left eye were well correlated (unlike for example in Graves Orbitopathy).
Yu-Wai-Man et al. (2013)
What symptoms do we find in neurogenic and myogenic conditions?
- Degeneration of brainstem
- Increased latency of blink response
- Restriction of voluntary eye movements with intact involuntary movements
- Abnormal MRI
- Muscle co-contraction
What did Yu-Wai-Man et al (2013) find out about CPEO and grey matter and cerebellar volumes?
Significant reduction in grey matter and cerebellar volumes for both types of CPEO patients
On subgroup analysis, the reduction in total grey matter and cerebellar volumes was apparent for patients with CPEO+, but not for those with pure CPEO phenotypes
What conditions do we need to differentially diagnose CPEO from?
- Congenital fibrosis of the extraocular muscles (CFEOM; children born with very restricted ocular motility and sometimes a ptosis)
- Myasthenia Gravis (MG)
- CNIII palsy or multiple CN palsies
- Supranuclear gaze palsy – these will show improvement in movement on doll’s head testing, whereas CPEO will remain unchanged.
- Graves Orbitopathy (GO) (and other mechanical disorders)
- Oculopharyngeal dystrophy
What is the aetiology of Oculopharyngeal Dystrophy?
Autosomal Dominant caused by short triplet repeat expansion (DNA mutation)
What are non-ocular characteristics of Oculopharyngeal Dystrophy?
- Onset - 5th decade of life
- Pharangeal weakness - difficulty swallowing
- Facial and limb weakness
- Pain in proximal muscles
What are the ocular characteristics of Oculopharyngeal Dystrophy?
Mimics CPEO
- Progressive bilateral ptosis
- OM, orbicularis and Bells Phenomenon usually intact - may develop limitation of elevation later (different to CPEO)
- Saccades - reduced (also in CPEO)
What investigations give us a differential diagnosis of CPEO?
- 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
Is muscle biopsy conclusive evidence of CPEO?
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.
How do we manage CPEO (simply?)?
- Nutritional supplements (explored to inc. mitochondrial function but no effective evidence-base yet; Pfeffer & Chinnery, 2013)
- Gene therapy (no cases treated with this yet) and genetic counselling
- Full investigations may involve neurologist, cardiologist (ECG to rule our cardiac abnormalities), audiologist, dysphagia specialist and endocrinologist
What investigations are important in the management of CPEO?
All patients should have an ECG and fundus examination to identify Kearns Sayre syndrome which needs to be repeated annually in patients without evidence of heart conduction defects. The progress can be recorded but due to the bilateral nature of the disorder it reduces the value of Hess charts but fields of uniocular fixation may be useful.
As asymmetrical in early stages diplopia may occur which can be relieved by prisms. Due to potential anaesthetic dangers of heart block or pharyngeal muscle weakness local anaesthesia is preferred over surgery.
How do we treat transient/constant diplopia (appreciated by 28-63%) of CPEO?
- Prisms
- Occlusion
How do we treat Ptosis in CPEO?
- Ptosis props - glasses / haptic contact lenses with shelf
- Tape
What surgery do we do to manage CPEO?
- EOM / lids (Potential anaesthetic risks = LA; heart block/pharyngeal muscle weakness)
- Ptosis surgery – Resection of Levator tendon (milder cases) or Frontalis suspension (more severe cases).
But it runs a risk of causing serious exposure keratitis due to the associated poor orbicularis function and absent Bell’s phenomenon
As progressive they will likely require numerous surgeries
What type of strabismus is most common in CPEO?
The strabismus is typically horizontal (exo more common than esotropia)
What surgery type should we do on EOMs in CPEO?
- Bimedial resections (sometimes bilateral LR recess and MR resect)
- Resections
- Bilateral LR recession and ipsilateral MR resection
Recessions due to restrictive nature
What are associated cognitive disorders with CPEO?
Impaired mitochondrial energy production result in dysfunction of all energy-dependent cell functions (Finsterer, 2012)
What is myotonic dystrophy?
Hereditary disorder of muscle fibre membrane that’s autosomal dominant (caused by triplet repeat expansion in the dystrophia myotonica protein kinase (DMPK) gene)
Affects 1/8000
What does Myotonic Dystrophy typically affect?
Causes an inability of muscles to relax after contraction and typically affects:
- Muscle of mastication
- Muscles of the hand and forearm
- Tongue
- Shoulders
- Legs
What are the ocular symptoms of myotonic dystrophy?
- Symmetrical ophthalmoplegia
- Sluggish miotic pupils
- Bilateral ptosis
- Retinal changes - pigmentry retinopathy
- Cataract – e.g. ‘snowflake cataract’
- Meibomian gland dysfunction - epihoria
What are the non-ocular (general) symptoms of myotonic dystrophy?
- Facial weakness
- Sagging jaw, thin neck
- General weakness
- Baldness
- Cardiac conduction defect (90%)
What do biopsies reveal of myotonic dystrophy?
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
What is Ocular Myositis? Aetiology?
Inflammatory process involving one or more EOM
Subgroup of idiopathic orbital inflammatory syndromes (IOIS)
Aetiology: Often following respiratory tract infection - ? autoimmune response
When does Ocular Myositis tend to present and in who?
Majority present between 18 - 40 years (range 9 - 84)
Approx. 2:1 F:M
What are symptoms of Ocular Myositis?
- 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% don’t experience pain yet this is considered a main symptom (painful diplopia)
Affects horizontal recti first followed by vertical recti
What progression of muscle changes do we see in ocular myositis?
- 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
What will be diplopia look like in Ocular Myositis?
Main symptoms is painful diplopia. When only one muscle is affected it’ll be paretic in the direction of the muscle OR mechanical in the opposite direction due to the inflammatory process preventing adequate muscle relaxation.
What is Ocular Myositis a subgroup of?
Part of subgroup of idiopathic orbital inflammatory syndrome characterised by EOM swelling that’s uni or bilateral, acute or chronic.
In severe cases there may be lid swelling, chemosis or proptosis
What does Ocular Myositis need to be differentiated from?
- Graves Orbitopathy
- Idiopathic orbital pseudo-tumour
- Orbital cellulitis
- Orbital rhabdomyosarcoma
How can Ocular Myositis and Graves’ Orbitopathy be differentiated from each other?
- Lid retraction and lid-lag which are absent in orbital myositis
- Pain often severe in Orbital myositis
- Thyroid function normal in orbital myositis
- Onset is usually more acute in orbital myositis
- Graves’ is usually bilateral
- CT scans show myositis often involve the EOM tendon that’s usually spared in Graves’
What is the management plan for Ocular Myositis?
Make comfortable with prisms whilst waiting for recovery
- Occlusion
- BT
- Corticosteroid treatment (if acute orbital myositis it can become chronic so early use of systemic steroid can reduce risk)
If experiencing persistent motility issues, if stable a minimum of 3 months then surgery can be considered
What is Orbital Pseudotumour also known as?
Idiopathic orbital inflammatory disease (IOID)
What is IOID/Orbital Pseudotumour?
Nonspecific, non-neoplastic inflammatory process of the orbit
Accounts for 8-11% of orbital tumours
Possibly caused by infection, autoimmune disorder and aberrant wound healing
Acute onset over a period of days/weeks (onset at any age but more likely in adults)
What is orbital myositis a subgroup of?
Orbital myositis is a subgroup of idiopathic orbital inflammatory disease (IOID) syndrome, which remains a diagnosis of exclusion. It can affect any orbital structure most commonly affecting lacrimal gland, orbital fat and EOMs – enlargement of these structures and enlarged orbital fat in neuroimaging.
What are the ocular characteristics of Orbital Pseudotumour/IOID?
- Proptosis (82%)
- Periorbital oedema
- Mechanical limitation of eye movements (54%)
- Pain with and without movement of the eyes
- Diplopia
- Erythema (redness of skin)
- Visual acuity loss (38%)
What can be seen in a CT scan in an orbital pseudotumour/IOID?
- Enhancement 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 with steroids
How do we diagnose Orbital Pseudotumour / IOID?
- Often by exclusion
- Lab tests normal
- Orbital imaging
- Biopsy
How do we treat Orbital Pseudotumour/IOID?
- Steroids
- Orbital Decompression
- Low Dose Radiation Therapy
What is the prognosis of Orbital Pseudotumour/IOID?
- Long term is favourable
- 30% recurrence rate
What are the types of orbital tumours?
- Primary tumour of the muscle (Rare) like a haemangioma
- Secondary tumour - infiltration of the tumour into EOM from orbit/adjacent sinus/bones like a Lymphangioma
- Metastases
Commonly from skin/breast cancers - Enlargement of Muscle
Infiltration of tumour (muscle weakness and mechanical restriction) - Mass effect within orbit/space occupying lesion
Mechanical restriction
When does an Orbital Rhabdomyosarcoma present?
Presents in childhood,
Typically <5 yrs,
70% <10yrs
What is Orbital Rhabdomyosarcoma?
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
Head and neck (around eyes) 35-40%, genitourinary tract 20%, extremities 20%, chest/lungs 10-15%
What symptoms do children with Orbital Rhabdomyosarcoma experience?
- Proptosis
- Recent onset diplopia
- Rapid vision changes
- Restricted motility
(Eade et al., 2017)
Case Study - See slides 44 onward
How might an orbital tumour affect the EOMs?
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.
What investigations can we do to diagnose an orbital tumour?
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.
What can orbital tumours result in?
- Orbital tumours can result inorbital congestion, vascular occlusion, and optic nerve compression.
- 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
What is the non-strabismic management of orbital tumours?
Management of tumour may involve:
- Intralesional injection using fibrin glue or bleomycin to solidify and reduce the volume of the tumour,Surgical debulking may follow.
- Surgery - orbitotomy or orbital exenteration
- External beam radiotherapy
- Chemotherapy
- Oral propranolol is a treatment option of orbital infantile hemangioma
Surgical removal of the tumour frequently leads to post-operative ocular complications
What is Orbital Cellulitis?
Orbital cellulitis is an infection (infective disease) that involves the soft tissues posterior to the orbital septum, including the fat and muscle within the bony orbit (systemic symptoms).
It can be associated with severe sight and life-threatening complications and therefore requires prompt diagnosis and initiation of treatment.
What age group are more likely to develop orbital cellulitis?
Paediatric population
How can orbital cellulitis be classified?
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.
What are the 5 types of orbital cellulitis (Chandler Groups 1-5)?
- Preseptal = Inflammatory edema
Inflammatory edema limited to the eyelid - Postseptal = Orbital Cellulitis
Inflammation including contents posterior to the septum - Postseptal = Subperiosteal Abcess (SPA)
Purulent collection between bony orbit and periorbita - Postseptal = Orbital Abcess
Purulent collection within the orbit itself - Postseptal = Cavernous Sinus Thrombosis
Retrograde Phlebitis
What are the clinical characteristics of Orbital Cellulitis?
- Periorbital oedema
- Ocular pain
- Proptosis
- Chemosis
- Restricted ocular motility - ophthalmoplegia
- Reduced visual acuity
Patients will likely complain of unilateral swelling, pain and erythema of the eyelid. They may have symptoms of systemic involvement such as malaise, fever and anorexia. Patients presenting with orbital cellulitis will likely complain of asymmetry of the eyes, chemosis, pain on eye movements, decreased vision and ophthalmoplegia.
Concurrent symptoms of headaches, neck pain, photophobia and cranial nerve palsies should raise the suspicion of intracranial pathology and cavernous sinus thrombosis.
Conservative management options are often preferred over surgery in patients with orbital cellulitis.
What should the presence of diabetes or immunosuppression make you suspicious of?
Orbital Cellulitis
What are the three main components of investigation in orbital cellulitis?
Examination of the patient should have three main components: the eye, the nose and the neurology of the patient. Examination should ideally be repeated four to six hourly to ensure no progression of symptoms.
What should you examine in orbital cellulitis?
Examination of the eye should ascertain signs of chemosis, degree and position of proptosis, relative afferent pupillary defect, diplopia, visual acuity, colour vision and discrimination, ocular movements, and inspection of the optic disc.
Can do blood investigations, CT and radiology also
