myogenic palsies Flashcards
what are examples of myogenic palsies
chronic progressive external ophthalmoplegia
cleo, cpeo+ , myotonic dystrophy
ocular myositis
tumours of muscle e.g. rhabdomyoscarm
define myogenic palsy
a primary disease of a muscle causing it to underact
what is cpeo
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
aetiology of cpeo
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+
what is cpeo+
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
what is Kearns Sayre syndrome
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
why are the eom’s affected in cpeo
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)
what is found for both neurogenic and myogenic palsies
degeneration of brainstem
increased latency of blink response
restriction of voluntary eye movements
abnormal mri
muscle co contraction
what is a common finding for both cpeo and cpeo+
significant reduction in grey matter and cerebellar volumes for both types of cpeo patients q
what structures are affected in cpeo +
muscle but also peripheral nerves and affected in cpeo+
what are the differential diagnosis for cpeo
cfeom - congenital fibrosis for the eom
myasthenia gravis
3rd nerve palsy
graves rbitopathy
oclopharangeal dystrophy
what is ocularpharanogeal dystrophy
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
what is necessary for the 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 for the presence 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 is cpeo managed
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
how would ocular symoptins and signs of cpeo be treated
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)
what eom surgery is done for people with cpeo
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)
what are the associated cognitive disorders associated with cpeo
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
what is myotonic dystrophy
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
what are the ocular features of myotonic dystrophy
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
what are the general features of myotonic dystrophy
General
Facial weakness
Sagging jaw, thin neck
General weakness
Baldness
Cardiac conduction defect (90%)
what are the general features of myotonic dystrophy
General
Facial weakness
Sagging jaw, thin neck
General weakness
Baldness
Cardiac conduction defect (90%)
what is ocular myositis
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
ocular 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% do not c/o pain!
Affect horizontal recti first followed by vertical recti
how do the muscles change in eom
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 are the differential diagnosis for ocular myositis
GO
Idiopathic orbital pseudo-tumour
Orbital cellulitis
Orbital rhabdomyosarcoma
what are the management options for ocular myositis
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.
what is a orbital pseudo tumour / idiopathic orbital inflammatory disease
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
what are the ocular characteristics of orbital pseduotumour
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%)
what is ocular myositis is a subgroup of
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
how are orbital pseduotumours diagnosed
Diagnosis
Often by exclusion
Lab tests normal
Orbital imaging
Biopsy
how is orbital pseudo tumour treated
Treatment
Steroids
Orbital decompression
Low dose radiation therapy
what is the prognosis for pseduotumour
Prognosis
Long term is favourable
30% recurrence rate
what are the types of orbital tumours
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
what are the characteristics of orbital tumours
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
what are orbital rhadbomyarcoma
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%
what would a child with orbital rhabdomyscarmo present with
child with protoptosis
recent onset diplopia
rapid vision changes
restricted motility
what would you find in a case example
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
what further investigations are necessary
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.
what management options would there be for orbital rhabdoscarmo
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
what would you find on histology for someone with cpeo
histopathology demonstrates ragged red fibres
a marker for dysfunction of mitochondrial dna
ragged fibres denote the absence of cytochrome oxidase
what is the aetiology of orbital cellulitis
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.
what are the clinical characteristics off orbital cellulitis
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.
what is the aetiology of orbital tumours
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.
how would you diagnose a 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.
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
