Aetiology of Neurogenic Palsies Flashcards
What nerve goes through the nerve nucleus in the midbrain, through the cavernous sinus and through the SOF?
Trochlear IV Nerve
What nerve originates at the pontomedullary junction, goes through the cavernous sinus, SOF and annulus of zinn?
Abducens
What nerve is located in the midbrain, passes along the cavernous sinus, through the SOF where it splits into inferior and superior divisions before going through the common tendinous ring?
Oculomotor
Which nerve is contralateral?
Trochlear
Which nerve travels through the medial lemiscus, trapezoid body and cortiospinal tract?
Abducens
Which nerve travels around the periaqueductal grey matter and around the inferior colliculus before travelling contralaterally to its muscle?
Trochlear
What are the neural pathways separated into?
Supranuclear pathway
Cranial Nerve Nuclei
Infranuclear (focusing on this in this lecture)
EOMs
Globe
Why can nerve palsies occur?
Anything that interrupts neural blood supplies such as:
- Interruption of blood supply
- Intracranial vascular abnormality
- Space occupying lesion
- Ophthalmoplegic migraine
- Trauma
- Surgery
- Changes in intracranial pressure
- Diseases (e.g. diabetes, multiple sclerosis)
- Inflammatory conditions (e.g. meningitis)
- Infections
- AIDS
- Stroke
What are Microvascular causes of nerve palsies?
- Due to ischaemic attacks which are small vascular accidents as a result of a blockage or bleed
- Isolated palsies are more common in the elderly due to these (Choi et al., 2019)
- High recovery rate (Jung & Kim, 2015)
What is the most common aetiology of nerve palsies?
Microvascular (Choi et al., 2019)
Which cause of nerve palsies has a high recovery rate (Jung & Kim, 2015)?
Microvascular causes
What risk factors should you ask about in reference to microvascular causes of nerve palsies?
- Diabetes
- Arteriosclerosis - Clogged artery, high cholesterol
- Hypertension - Hypertensives need to be asked about
According to Choi et al. (2019) what is the most common aetiology of isolated nerve palsies in >50’s?
Microvascular
What does CCF stand for?
Carotid Cavernous Fistula
According to Choi et al. (2019) what is the most common aetiology of isolated nerve palsies in <50’s?
Less defined aetiology so ‘other’
According to Dhume & Paul (2013) what % of non-microvascular palsies have vascular risk factors?
60%
What are microvascular risk factors?
- Age
- Hypertension
- Diabetes
- Hypercholesterolemia
- Arteriosclerosis
- Smoking
- Coronary artery disease
- Alcoholism
What did Patel et al (2005) find about VI nerve palsy, diabetes and hypertension?
Diabetes gives VI palsy a 6x increase
Diabetes + Hypertension gives VI palsy a 8x increase
Hypertension = 0x
What did Jacobson et al (1994) find out about oculomotor nerve palsies, diabetes and hypertension?
Diabetes gives III palsy a 5.75x increase
Left ventricular hypertrophy gives a 5.5x increase
Hypertension = 0x
What is left ventricular hypertrophy?
Thickening and weakens of lower left heart chamber
Uncontrolled high blood pressure can cause this.
What happens in diabetes pathophysiology?
Jacobson et al. (1994) -
Diabetes: alterations in blood-nerve barrier causing demyelination and conduction block.
Recovery occurs as remyelination occurs.
How many risk factors are associated with longer recovery time in microvascular palsies?
Jung & Kim (2015) – Patients with 2+ risk factors or intracranial abnormalities were associated with longer recovery time for microvascular palsies.
How often should we follow up a microvascular nerve palsy?
Follow-up in a 1 or 2 weeks to monitor the progress and thereafter see them on a 2-3 weekly basis as by 9 weeks may have spontaneously recovered
What is recurrence rate of VI (6th) nerve palsy according to Sanders et al. (2002)?
- 31% had subsequent episode
- 14 had one recurrence
- 1 had four recurrences
But duration of follow-up ranged from 2-13yrs
What is a stroke?
When blood supply to part of the brain is cut off
What is an ischaemic stroke?
Decreased blood supply caused by a blockage (most strokes)
What is a Haemorrhagic stroke?
Bleeding in or around the brain which is more rare, making up 20% of cases
What is a Transient Ischaemic Attack (TIA)?
Acute vascular disturbance where the disability lasts less than 24 hours
What is an Infarction?
Development of an area of localised tissue death (necrosis) as a result of lack of oxygen (anoxia) caused by an interruption in blood supply e.g. occlusion of an artery.
What is Thrombosis?
Aggregation of platelets, fibrin, clotting factors and cellular elements of blood which become attached to the interior wall of a vein or artery
How much time does Microvascular CNIII take to progress to maximal ophthalmoplegia?
Capo et al. (1992) - Average interval from onset to development of maximal ophthalmoplegia in microvascular CNIII is 3.3 days
Median - 10 days but the range is 3 - 23 days
How long can it take for complete CNIII to show maximal ophthalmoplegia in microvascular CNIII?
3.3 days
Need to tell the patient it can get worse before it gets better as they may get drooping (ptosis) and be prescribed an eyepatch
What, as well as microvascular CNIII, can cause maximal ophthalmoplegia CNIII in 3 days?
Posterior Communicating Artery aetiology (which is far more serious so do not use the 3 days as a way to determine the cause of the palsy)
What symptoms arise from a microvascular CNIII palsy?
Pain & sudden diplopia in both ischaemic or compressive disorders
In Jacobson et al. (1995) which palsies recover the quickest?
Non-progressive palsies recovered quicker (mean 7.2 weeks)
Why do we expect CNIII to get worse before getting better?
Thought to get worse before getting better because of intraneural compression and further microvascular ischaemia from oedema after initial insult/onset
What do we suspect if someone has a CNIII and dilated pupils that do not respond to light?
Assume compression by a posterior communicating artery aneurysm almost aways results in pupil involvement.
‘Fixed and dilated’
Posterior Communicating Artery always involves an aneurysm so needs to be imaged right away. If someone has a blown pupil that is not reactive to light t’s an urgent referral to A&E, never let them go home without it!
If someone has a complete CNIII with Pupil Sparing what is the likely cause?
Likely microvascular
Caution in young patients <50yo as aetiology is less defined
If someone has a complete CNIII without Pupil Sparing what is the likely cause?
Compression by expanding posterior communicating artery aneurysm
If someone has an incomplete CNIII what is the likely cause?
It might yet become a complete CNIII with pupil involvement so they need to have urgent neuroimaging as we may be able to see the start of compression.
What is a “pupil sparing CNIII palsy”?
A “pupil-sparing 3rd nerve palsy” refers only to a complete 3rd nerve palsy in which all the extraocular muscle it serves are without any activity and in which the pupil remains normal in size and reactivity.
What does the flowchart for CNIII and pupils look like?
See Slide 29
What is ‘aberrant regeneration’ also known as?
Sometimes referred to as: ‘Misdirection Syndrom0e’ or ‘Oculomotor Synkinesia’
What nerve palsy does aberrant regeneration happen in?
CNIII
When does aberrant regeneration occur in CNIII palsies?
6+ weeks after onset
What is often the cause of aberrant regeneration in CNIII palsies?
trauma or space-occupying lesions
What doesn’t happen in microvascular palsies?
Aberrant Regeneration
What is aberrant regeneration?
A misdirection of axons that occurs in the process of repair following mechanical disruption of a nerve. Looks like a retraction/fluttering of eyelid due to the miscommunication of signals to the nerves. New growth of nerves that is going all wrong.
What are the features of aberrant regeneration in a CNIII palsy?
- Retraction of upper lid on down gaze
- Elevation of upper lid on adduction
- Constriction of the pupil on elevation, depression or adduction
- Adduction on attempted elevation (and occasionally on depression
All of these can occur, or they can occur in isolation
What does PEARL stand for?
Pupils equal and reactive to light
See slide 32
Which cranial nerve is the thinnest, has longest intracranial route and is most vulnerable?
CNIV
What trauma causes CNIV palsy?
Closed head trauma
What trauma causes CNIV palsy?
Downward displacement of the brainstem
What trauma causes CNIII palsy?
Least frequently affected by trauma, frontal blow to accelerating head
What can shaken baby syndrome lead to?
Isolated or bilateral palsies may occur
What is shaken baby syndrome also known as?
Also known as NAI in clinic which is a non-accidental injury
What is an aneurysm?
A dilatation in the wall of an artery supplying blood to a specific area. Burst = haemorrhage. Can clip an aneurysm to prevent the haemorrhage.
What is a subdural haematoma?
Bleeding under the membrane covering the brain called, the dura. Sometimes after head injury.
What is a tumour (neoplasm)?
Abnormal tissue growth
What is an arteriovenous malformation (AVM)?
An arteriovenous malformation (AVM) is a rare tangle of arteries and veins with no capillaries between them
What is a fistula (dural arteriovenous fistula)?
Irregular connections between arteries and veins occurring in the tough covering over the brain or spinal cord (dura mater). (abnormal passageway between arteries and veins)
Where might an aneurysm come from?
Persistent localised dilations of a blood vessel wall which may result from a developmental defect or be acquired from:e.g. acquired degenerative change, infection, inflammation, trauma
Symptoms occur from pressure, bleeding or rupture
Aneurysm facts from Barrow & Reisner (1996)
- Ruptured aneurysm can cause intracerebral / subarachnoid haemorrhage
- 90% asymptomatic until rupture
- Only 10% present pre-rupture with symptoms of mass effect
- Interval between warning signs to rupture - 1 day to 4 months (median 14 days)
What is the prognosis following a ruptured aneurysm?
- 12% of patients die before receiving medical attention,
- 40% of hospitalized patients die within 1 month of rupture
- More than 1/3 of survivors have major neurological deficits
(Barrow & Reisner, 1996)
What are the symptoms of an aneurysm?
- Patients describe as ‘the worst headache of their life’ (& look at the pupils)
- Absence of pain is unusual BUT doesn’t rule out aneurysm
- Medical emergency – aim is to repair the artery and stop bleeding with immediate surgery
- They may leak before they rupture
If a patient presents with diplopia and a terrible headache what should you do?
Treat it like a medical emergency as it is likely an aneurysm
What can an internal carotid and posterior communicating artery (PCA) aneurysm lead to?
CNIII palsy
What can intracranial portion of the internal carotid aneurysm lead to?
Compression of the anterior visual pathway
What can an aneurysm of the cavernous sinus lead to?
CNIII & VI palsy
OR
Isolated VI nerve palsy that is frequent with ipsilateral Horner syndrome
What is aneurysm clipping?
Small metal clip is placed across the neck of the aneurysm to prevent blood flow to it.
What are arteriovenous malformations (AVMs)?
- Collection of tightly tangled, abnormal and enlarged blood vessels between arterial & venous circulations
- Blood is shunted from arteries to veins without an intervening capillary bed
- Rare, congenital
- Usually become symptomatic during 2nd & 3rd decades of life
When do AVMs become symptomatic and what are the symptoms?
- Usually become symptomatic during 2nd and 3rd decades of life
- Presence of objective bruit (whooshing noise)
- Headache (often misdiagnosed as a migraine)
Occur as a result of compression, haemorrhage, ischaemia or vascular steal
What is a Carotid-Cavernous Fistula (CCF)?
Abnormal connection between carotid artery and cavernous sinus
Highly pressurized arterial blood can be transmitted directly into the cavernous sinus
What are the symptoms of high flow CCF?
- Often after head injury
- Pulsating exophthalmos
- Conjunctival chemosis (red eye)
- Cranial Bruit (whooshing sound)
- Diplopia in 60-70%
What are the symptoms of low flow/dural (indirect) CCF?
- Minor signs and symptoms
- Onset of redness one or both eyes
- Mild proptosis, minimal eyelid swelling, conjunctival chemosis
- May or may not be cranial bruit (whooshing)
- Diplopia - most often 6th nerve palsy
- 20-30% result in visual loss
How does Cavernous Sinus Syndrome happen?
- Trauma (Basal/base of skull fracture, operative trauma to cavernous sinus after skull base surgery)
- Infection (Mucormycosis, mycobacterium, herpes zoster)
- Vascular (CC fistula, aneurysm, thrombosis)
- Tumour (e.g cavernous sinus meningioma)
- Inflammatory disease (Tolosa-Hunt syndrome, sarcoidosis)
What is Cavernous Sinus Syndrome?
Any disease that affects the cavernous sinus
What are the characteristics of cavernous sinus syndrome?
- 3rd, 4th, 6th nerve palsy, alone or in combination (usually ipsilateral)
- Oculosympathetic paralysis
- Proptosis
- Ophthalmic and maxillary division of 5th nerve may be affected
- Periorbital or hemicranial pain
- Trigeminal neuralgia (chronic pain disorder that causes sudden, severe facial pain in the distribution of the trigeminal nerve)
How is cocaine related to nerve palsys?
Cocaine is a vasoconstrictor
Consider Cocaine use in differential diagnosis for oculomotor abnormalities especially in young patients.
(Migita et al, 1997)
Can precipitate or exacerbate Myasthenia Gravis symptoms.
What are the systemic sign and symptoms of GCA?
Jaw claudication (pain in the jaw whilst chewing)
Headache
Weight loss
Malaise (general feeling of being ill or having no energy)
Anorexia
Scalp tenderness
Abnormal temporal artery (tender, nodular, or non-pulsating temporal artery)
Myalgia (muscle pain)
Fever
Anaemia
Neck pain
What is Giant Cell (Temporal) Arteritis (GCA)?
Inflammatory disease of blood vessels. Affects artery walls, predominantly extracranial vessels - particularly superficial temporal arteries with up to 70% irreversible visual loss.
Occult giant cell arteritis - where there are no systemic symptoms (ocular only)
Median age of onset: 75 years. Rare under 50 years
(Kawasaki and Purvin, 2009)
What are the ocular symptoms of GCA?
- Amaurosis fugax (painless, transient, monocular or binoc visual loss)
- Visual loss
- Diplopia
- Eye pain
What are 4 types of ocular ischaemic lesions?
- Anterior ischaemic optic neuropathy (lack of blood supply to ON)
- Central retinal vein occlusion
- Cilioretinal artery occlusion
- Posterior ischaemic optic neuropathy (lack of blood supply to retrobulbar ON)
What does ESR in GCA stand for?
Erythrocyte Sedimentation Rate
What does GCA stand for?
Giant Cell Arteritis
What is ESR in GCA?
ESR: blood test to measures how quickly red blood cells fall to the bottom of a tube.
Measures rate of inflammation.
Inflammation causes red blood cells to stick together and fall faster.
What are the rates of ESR in GCA?
Normal: 0-30 mm/hr
Generally lower in the young
96% of GCA patients had ESR>50mm/h – hallmark of GCA
(Martinez-Taboada et al, 2000)
What is Herpes Zoster Ophthalmicus?
It’s a reactivation of varicella zoster virus that can spread to the skin via afferent nerves. In healthy individuals it lies dormant in the dorsal root nerve ganglion after chickenpox.
What % of the herpes zoster infection does herpes zoster ophthalmicus account for?
Herpes zoster ophthalmicus accounts for 10-20% of cases of herpes zoster infection. (Liesegang, 2008)
What are the symptoms of herpes zoster ophthalmicus?
Painful, vesicular, dermatomal rashes affecting the ophthalmic division of the trigeminal nerve (V1).
Muscle palsies may be ipsilateral, contralateral or bilateral, and may affect one or more nerves
Who are most commonly affected by herpes zoster ophthalmicus and how is it treated?
Can affect any age, but more common in elderly or immuno-compromised
Treated with anti-viral therapy (e.g acyclovir)
What other inflammatory conditions can cause nerve palsies?
- Meningitis
- Encephalitis
- Poliomyelitis
- Tertiary Syphilis (late stage)
- Tolosa-Hunt Syndrome
What is Tolosa-Hunt Syndrome?
Non-specific granulomatous inflammation in anterior part cavernous sinus / SOF area
What are the symptoms of Tolosa-Hunt Syndrome?
Possible involvement 3rd, 4th, 6th nerves with severe constant pain
Visual loss if Optic Nerve involved
Proptosis
Sluggish Pupil
How is Tolosa-Hunt Syndrome diagnosed and treated?
Diagnosis: CT scan, ESR may be raised
Treatment: Systemic steroids (e.g. prednisolone)
What does SLE stand for?
Systemic Lupus Erythematosus
What are the symptoms of Systemic Lupus Erythematosus (SLE)?
Immunological disorder affecting connective tissue and nervous system
Nerve palsy may be due to vaso-occlusion of small vessels
No cure, pain relief used, if severe immunosuppressives
What is Sarcoidosis?
Granulomatous disease
Isolated or multiple nerve palsies reported, may be accompanied by pain
No cure, but treated with steroids
What is Guillan-Barre Syndrome?
Acute inflammatory demyelinating polyradiculoneuropathy – Aetiology not fully understood. May occur after viral infection.
Sudden, acute motor paresis peaking within 4 weeks
Ocular involvement to varying extent: ophthalmoplegia, fixed dilated pupils, optic neuritis, facial nerve palsy
Who does Guillan-Barre Syndrome affect most and how is it treated?
Slightly more common in males than females, can affect any age but most common 20-50 yrs age
Treatment: Intravenous immunoglobulin treatment, steroids, plasma exchange (treatment removes antibodies from blood
What is Miller Fisher Syndrome?
Possibly a variant of Guillan-Barre
May occur after upper respiratory tract infection
What are the symptoms of Miller Fisher Syndrome?
- Ophthalmoplegia – usually symmetrical (divergence paralysis, impaired smooth pursuit have also been reported)
- Ataxia
- Hyporeflexia or areflexia
What is the diagnosis and management of Miller Fisher Syndrome?
agnosis: Increased protein in CSF from lumbar puncture.
Management: As for Guillan-Barre. Good prognosis.
How is Demyelination related to nerve palsies?
Sometimes the first sign of MS is a nerve palsy. Disease of the central nervous system and is remitting and relapsing in nature. Ask if has happened before, need more than one episode to be diagnosed with MS.
Who is Demyelination/MS most common in and when should you suspect MS in a nerve palsy?
Onset: generally 15 – 45 years
Suspected in young adults with isolated nerve palsy
May have other symptoms or history of previous episode
What sort of infections (examples) can cause nerve palsies?
Cytomegalovirus (Greco et al, 2006)
Herpes Zoster (Shin et al, 2007)
Lyme Disease (Sharma & Biswas, 2010)
Measles (Werner et al, 1983)
Syphilis (Singh et al, 2020)
Covid-19 (Francis, 2021) – lots of patients presenting with 6th
What is Gradenigo’s Syndrome?
Infection of middle ear leading to petrositis and affecting 6th nerve as it crosses petrous part of temporal bone
What are the symptoms of Gradenigo’s Syndrome?
- Ipsilateral pain of trigeminal nerve distribution
- Constant ottorhea (ear discharge)
Should ask patients in their recent history about ear infections
How might HIV/AIDS (acquired immune deficiency syndrome) be involved in nerve palsies?
When a person becomes infected with HIV, the immune system doesn’t work as well. As a result, cancers may develop more quickly and become harder to treat, since the immune system usually helps fight cancerous cells before they turn into tumors. People who are taking anti-HIV medicines—medicines that help boost the immune system—may be better able to benefit from anticancer treatments.
Infections:
Parasitic e.g toxoplasmosis
Fungal e.g cryptococcosis
Bacterial e.g. Syphilis (Singh et al, 2020)
Neoplasms (abnormal growth of tissue)
Greater risk of cancers including: Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer.
Vascular (high risk of infarct or haemorrhage)
How does one end up with multiple cranial nerve palsies?
Infectious
Neoplastic
Inflammatory
Traumatic
Idiopathic
Less common:
Cavernous Sinus Lesions,
Aneurysms,
Herpes Zoster, Meningitis, Encephalitis,
Tolosa-Hunt, Miller Fisher.
What can cause congenital neurogenic palsies?
- Congenital conditions
Hydrocephalus
Cerebral palsy
Inherited SO palsy - Intoxications from mother
Lead poisoning, drugs, alcohol - Birth trauma e.g. forceps used
In Paediatrics what is the most common cause of 4th, 6th and multiple (3rd, 4th & 6th) nerve palsy?
4th = Congenital
6th = Neoplasia, post-viral & idiopathic
Multiple = Traumatic
At how many weeks are we expecting 6th nerve palsies in paediatrics to resolve?
12.3 weeks (Chang & Borchert, 2022)
What are the most common causes of 6th nerve palsies in paediatrics? Both isolated and non-isolated?
Isolated: post viral / post vaccination, idiopathic, tumour!
Non-isolated: Tumour, Increased ICP (non tumour), trauma
What’s the most likely cause of a non-isolated VI nerve palsy?
Tumour
If a VI nerve palsy is getting worse and not better what should we suspect?
Tumour.
E.g. post-viral will get back to normal as blood supply reestablishes itself but if it’s getting worse then think tumour.
Can be from viral infections in paeds, 6th nerve palsy in child can be benign and recurrent but need to exclude other causes (Knapp and Gottlob, 2004)
What are some non-neurogenic (not caused by issues with the nervous system) causes of nerve palsies?
Nucleus of CN: aplasia (absent); hypoplasia (partial development); maldevelopment
Nerve: as above or incorrect distribution
Muscle: aplasia; abnormal insertion, check ligaments or connections
Orbit: malformation
When is recovery more likely in nerve palsies?
When treatment of underlying cause successful (Park et al, 2008)
Notably in tumours after treatment (Huang et al, 2017)
Microvascular aetiology (Capó et al, 1992)
If the word ends in ‘oma’ what is it?
A tumour
What is a skull-base tumour?
Skull base tumourcan be any type of tumour that forms in the skull base, which is the bottom of the head and the body ridge in the back of the eyes.
E.g. Pituitary adenomas & Craniopharyngioma
What is the most common aetiology in children with CN VI palsy?
Tumour is most common aetiology in children with 6th nerve palsy
(Chang & Borchert, 2022)
What are the most commonly affected nerves in tumours?
CNVI and CNIII
What nerve palsy do pituitary tumours most commonly cause?
Pituitary tumours most commonly cause 3rd nerve palsies
(Kim et al, 2007)
What did Volpe & Lessell (1993) find out about tumours that are presumed idiopathic?
Volpe and Lessell (1993) described 7 cases of remitting sixth nerve palsy in skull base tumours.
Recovery time: 1 week to 18 months
So they might be tumours and not idiopathic
What reasons did Volpe & Lessell (1993) consider might be mechanisms for recovery in tumours?
Possible mechanisms for recovery:
- Remyelination
- Axonal regeneraton
- Relief of transient compression
- Restoration of impaired blood flow
- Slippage of a nerve previously stretched over tumour
- Immune responses to tumour
When are tumours more likely to recover after treatment?
Huang et al. (2017)
Tumours such as nasopharyngeal carcinoma (NPC) can extend to the cavernous sinus and compress multiple cranial nerves.
Patients with CN palsy presenting 2 months before diagnosis were less likely to recover.
What is an Ophthalmoplegic Migraine?
Rare condition – sometimes called intracranial neuralgia
Unilateral headache
Followed by 3rd nerve palsy - partial or complete, pupil often affected
6th nerve may be affected and a suggested cause of recurrent 6th nerve palsy in children - in absence of any pathology
Will always be scanned as presents like an aneurysm but in these cases tend to be transient and come back to Orthoptics . Migraines can change the blood flow to the brain
What is an Intracranial Neuralgia also known as?
Ophthalmoplegic Migraine
What is Idiopathic Intracranial HYPERtension (IIH)?
(aka Benign Intracranial Hypertension; Pseudotumour Cerebri)
Increased intracranial pressure (in an alert and orientated patient)
Possibly due to reduced cerebrospinal fluid absorption
Occurs rarely in children
In adults: higher incidence in females and in the obese
Mx: Acetazolamide, relief following Lumbar Puncture
What are the main symptoms of Idiopathic Intracranial HYPERtension (IIH)?
- Headache
- Nausea and vomiting
- Papilloedema (swelling of optic disc)
- Pulsatile tinnitus
- 6th nerve palsy (unilateral/bilateral)
- 3rd & 4th also reported
(N.B. Also concomitant strabismus or decompensation has been reported)
When might Idiopathic Intracranial HYPOtension occur? What are the symptoms?
Following dural puncture (e.g. diagnostic lumbar puncture; accidentally during epidural anaesthesia)
Headache (and nausea), worse when upright, may occur after puncture
Extraocular muscle palsy is a rare complication
6th nerve palsy commonest – 3rd & 4th also reported
Unilateral or bilateral
Onset 1 – 3 days after puncture
(Nishio et al, 2004)
What must we do when we have an ‘unknown’ aetiology?
Some aetiologies may ‘unknown’, ‘presumed’ or ‘suspected’ so proceed with caution when diagnosis is unknown = see the patient more often in clinic
