Neuro-ophthalmology Flashcards
What are the aims when we perform a neurological examination?
- Do the clinical signs refer to a nervous system problem? (others that mimic = orthopaedic, cardiorespiratory or metabolic disturbances)
- What is the location of this lesion within the nervous system and is it focal, multifocal or diffuse?
- What are the types of disease process that can explain these clinical signs (think Vitamin D)
- How severe is the problem?
1st 2 questions answered by performing general PE and neurological exam.
Last 2 questions answered by looking at patient signalment, and progression with the anatomic diagnosis to determine the differentials.
Describe the steps of a neurological examination.
Observation - mental status, behaviour, posture, gait evaluation, involuntary movements, is the patient ambulatory etc.
Hands on - cranial nerves, postural reactions, spinal reflexes, muscle tone/size, nocioception, sensory evaluation
Why should we always try to identify the anatomic location of neurological lesions after performing our clinical and neurological exam?
- DDx list is almost entirely dependent on the anatomic location
Also helpful to know if lesion is focal, multifocal or diffuse as can help to further narrow differential list. - Number of diseases may only be diagnosed by excluding others mimicking a similary history and clinical presentation. If lesion isn’t localised deciding which diagnostics to perform and interpreting them can be challenging.
- Allows us to run more specific investigations - less cost for owners, less time to reach diagnosis and less risk for patient.
What are the regions with can anatomically localise to after performing a neurological examination?
- Forebrain
- Brainstem
- Cerebullum
- Spinal cord - segments C1-C5, C6-T2, T3-L3 and L4-S3
- Neuromuscular system (peripheral nervous system)
Localisation is not pathognumonic for any 1 particular neurological condition.
What makes up the cerebrum and what is its function?
Includes cerebrum and diencephalon and is the area of the brain rostral to the tentorium cerebelli
Cerebrum = cerebral cortex, white matter, basal nuclei.
Important for behaviour, vision, hearing, fine motor activity and conscious awareness of touch, pain, temperature and body position.
Basal nuclei = muscle tone and initiation of voluntary motor activity
Diencephalon = autonomic and endocrine function, VISION AND PLR (CN II - optic nerve) and emotional behaviour patterns associated with limbic system.
Also acts as sensory relay system to cerebral cortex for the functions of vision, hearing conscious awareness of pain (nociception) and awareness of body position (proprioception)
Describe the function of the brainstem.
Brainstem = regulatory centres for conciousness, cardiovascular system and breathing.
Links cerebral cortex to spinal cord
11 pairs of cranial nerves (CN II - XII) originate within this region.
Describe the function of the cerebellum.
Cerebellum = control the rate, range and force of movements without actually initiating any motor activity.
Co-ordinates muscle activity and smoothes movements once they have been induced by upper motor neurons.
Maintenance of posture (close association with vestibular nucleus) and regulation of muscle tone when the body is at rest or during motion.
Inhibitory influence on urination.
What are the spinal cord segments?
What do the segments of the spinal cord each contain?
Spinal cord segments - C1-C5, C6-T2, T3-L3, L4-S3
Contain cell bodies of the lower motor neurons (LMN)
Segments C6-T2 - LMN controlling thoracic limbs
Segments L4-S3 - LMN controlling the pelvic limbs
Lesions at these levels will affect corresponding limbs.
C1-C5 and C6-T2 lesions = tetraparesis and often postural reaction deficits in all limbs
C1-c5 or T3-L3- normal, sometimes increased spinal reflexes (upper motor signs)
C6-T2 or L4-S3 - reduced muscle tone and reduced spinal reflexes in thoracic/pelvic limbs (lower motor signs)
T3-L3 and L4-S3 = paraparesis and postural reaction deficits in hindlimbs
What is the peripheral neuromuscular system composed of?
Neuromuscular system = motor units
Composed of neuron cell body (within spinal cord grey matter or within the cranial nerve nucleus of the brainstem), its axon (leaves via ventral nerve roots to join successively a spinal nerve to a peripheral nerve), neuromuscular junction (cholinergic/nictotinic synapse) and muscle fibres.
Disease affecting any of these levels will manifest as signs of neuromuscular disease.
LMN = connects central nervous system to a target muscle.
Can see with peripheral neromuscular system lesions:
Neuropathy
Junctionopathy
Myopathy
As well as classifying the anatomic location of a neurological lesion how else should we further define it in terms of distribution?
Focal - all signs explained by one anatomic location
Multifocal - signs affecting multiple parts of the nervous system
Diffuse - affecting globally or symmetrically one or more parts of the nervous system
What mnemonic can be used to help determine a differential list for neurological problems?
VITAMIN D
V= Vascular
I = Inflammatory/Infectious
T = Trauma/Toxic
A = Anomalous
M = Metabolic
I = Idiopathic/immune mediated
N = Neoplastic/Nutritional
D = Degenerative
Describe the general progression of the different vitamin D differentials with neurological disease (draw the graph if you wish)
Vascular = improves with time
Inflammatory/Neoplastic- worsens dramatically in short space of time
Metabolic = wax and wane type signs
Degenerative - worsens gradually over time
Traumatic - improves with time
Describe the types of aetiologies we typically see with focal, multifocal and diffuse neurological disease.
Focal:
Vascular - focal and often asymmetric, peracute to acute onset, chronic to non progressive/regressive signs
Neoplastic - can be focal, chronic progressive signs
Trauma - peracute to acute signs, signs static or improve with time, can be symmetrical or asymmetical.
Inflammatory - can be focal, asymmetrical or symmetrical, acute, subacute or insidious onset with progressive signs.
(Occasionally degenerative)
Multifocal - infectious, inflammatory (loves multifocal presentation), neoplastic (often metastatic)
Diffuse - metabolic, toxic, degenerative
Idiopathic - specific to each syndrome, acute onset and generally non progressive/regressive.
What is the optic nerve an extension of? What neuro-ophthalmic roles does it have?
Not a true nerve but an extension of the brain!
Therefore pathology of the brain can often affect the optic nerve.
Central visual pathway - involved in sensory visual perception
Afferent (sensory) component of the pupillary light reflex and dazzle reflex
Describe the visual pathway. How many neurons are involved and how much decussation is there cats vs dogs vs humans)
3 consecutive neurons involved
- Neuron 1 represents the bipolar cells of the retina and receives visual information from the neuroepithelial cells of the retina (rods and cones)
- Neuron 2 = retinal ganglion cells, it’s axons lie in the optic nerve and continue through the optic chiasm and proximal part of the optic tract of the opposite side
(66% decussation in cats, 75% decussation in dogs, 55% humans) - Neuron 3 = cell body in lateral geniculate nucleus in the diencephalon. It’s axon projects to the visual cortex (mostly contralateral occipital centre) in a band of fibres called the optic radiation.
Describe the pathway for the generation of a PLR. What type of reflex is this?
Afferent = optic nerve (CN II)
Efferent = parasympathetic fibres occulomotor (CN III)
1.Bright light enters retina and initiates impulse that travels through to optic nerve, optic chiasm and optic tract.
2.The stimulus is the relayed to the pretectal nucleus within the rostral colliculus.
- Parasympathetic nucleus of the occulomotor nerver (CN III) is then stimulated in the mesencephalon and signal transmitted through is parasympathetic branch resulting in contraction of the iris sphincter muscle and constriction of the pupil.
A lesion in any of those regions can disrupt the PLR pathway.
Subcortical reflex - no involvement of the cortex/visual processing centre therefore IS NOT A TEST OF VISION but can help identify the location of a lesion in a blind animal.
Why do we see a consensual PLR?
Why is the direct PLR stronger compared to the consensual?
Due to decussation of axons within the PLR pathway
at the level of the optic chiasm
Most of the axons that then arise from the pretectal nucleus decussate again and synapse in on the parasympathetic component of the occulomotor nucleus (ipisilateral to the stimulated eye) in the mesocephalon.
Still some neurons that do not decussate and project to the contralateral side to the stimulated eye.
Proportion of axons that decussate at this level is higher than the ones that do not and explains why the direct PLR is stronger than a consensual PLR.
What methods have we got for assessing vision in the consult room?
Obstacle course evaluation
Menace response test
Visual placing reaction
Object tracking
How should an obstacle course evaluation be performed? What is its limitation.
Evaluates ability of animal to navigate in unfamiliar surroundings
Most reliable if perform binocularly or monocularly (but difficult to perform in small animals)
Light/dark conditions
Poorly sensitive method to assess subtle or unilateral visual impairment.
From what age can we assess the menace response?
May not be developed until 10-12 weeks
Response not a reflex are learnt behaviour - cortically mediated behaviour
IS an assessment of vision (unlike PLR/dazzle)
Describe the menace response? What neurons are involved in this pathway?
Menace = eyelid closure with/without head withdrawal produced by threatening or unexpected image suddenly appearing in the near visual field.
Afferent arc involves following neurons:
1. Bipolar cells of the retina - recieves impulses from the rods and cones
2. Retinal ganglion cells - axon lies within optic nerve and continues through optic chiasm and proximal part of the optic tract of the opposite side (due to decussation)
3. Lateral geniculate nucleus - axons then project to visual cortex via band of fibres known as optic radiation
Efferent arc is not well understood
Information generated in visual cortex is forwarded to the motor cortex via association fibres
Cortico-bulbar pathways of the facial nerve (CN VII) then transmit the motor information
Response requires intact facial nerve function!
Some experimental and clinical evidence for cerebellar involvement in the menace response efferent pathways also (unilateral cerebellar lesions can lead to ipsilateral menace response loss with normal vision) - neuronal pathways through cerebellum however are not known
What reflex should be tested alongside the menace to determine whether the absence of a blink is due to vision loss or the inability to blink?
What reaction would we see to the menace in a patient with facial paralysis unable to blink?
Palpebral reflex
If absent as well as defined menace response think facial nerve lesion.
If patient does have facial nerve paralysis should still see some retraction of the globe via the action of retractor bulbi (abducens)
Give a summary of the menace response pathway. What are the afferent and efferent arms?
Afferent = optic nerve (CN II)
Efferent = facial nerve CN VII (abducens CN VI for retractor bulbi)
- Menacing stimulus detected by retina
- Impulse travels down optic nerve, to optic chiasm and contralateral optic tract
- Impulse reaches lateral geniculate nucleus within thalamus
- Optic radiation to occipital/visual cortex
- Signal then travels rostrally and synapses in motor cortex
- Projection fibres through internal capsule, crus cerebri and longitudinal fibres of pons to synapse in pontine nucleus
- Transverse fibres of pons through the cerebellum, synapsing in cerebellar cortex
- Signal then travels through efferent cerebellar pathway to facial nuclei
- Signal relayed through right and left facial nerves synapsing on facial muscle - orbicularis oculi.
- Contraction of orbicularis oculi and generation of a blink and closure of eyelids
(Abducens may also stimulate retraction of the globe via retractor bulbi)
How is a visual placing reaction performed?
Dog or cat carried under chest towards table edge without letting its limbs touch the table.
On approaching the table the animal will reach out to support itself.
Requires intact visual and motor pathways.
What is the difference between peripheral and central blindness?
Peripheral blindness = any lesion along the visual pathway shared with the PLR pathways (i.e within eye, CN II, optic chiasm or proximal optic tract)
Central blindness = lesion in visual pathway not shared with the PLR pathway (a lesion caudal to thalamus, e.g distal optic tract, lateral geniculate nucleus, optic radiation or occipital cortex)
How can we test the integrity of the optic nerve?
Combining results of tests such as the PLR, menace, visual placing etc.
PLR = tests integrity of the optic nerve to the lateral geniculate nucleus but does not test the animals vision
Fundic examination and evaluation of the optic disc also indicated as part of examination of integrity of optic nerve in animals presenting with blindness.
Describe the pathway of the dazzle reflex? Is it a test of vision?
NOT a test of vision - subcortical (so can be present in a blind animal)
Reflex not a learnt response
Bright light shone into eye should cause a partial blink response
Afferent = optic nerve (CN II)
Efferent = facial nerve (CN VII)
- Bright light stimulus enters retina
- Travels through optic nerve, optic chiasm and optic tract
- Stimulus relayed to pre-tectal nucleus of rostral colliculus
- Signal transmitted to ipsilateral facial nucleus in brainstem
- Facial nerve then carries the efferent stimulus to orbicularis oculi resulting in a reflex blink.
What findings on examination may make you suspect a central cause to blindness.
CNS signs = change in mentation, seizures, change in behaviour, circling, head turn, head pressing, hemi-neglect syndrome (forebrain)
Cranial nerve deficits (brainstem)
Loss of postural reactions
Abnormal gait (ataxia with/without paresis)
What are the ddx for unilateral abnormal vision with a PLR deficit?
PLR deficit = peripheral blindness
Lesion affecting - ocular media, retina, ipsilateral optic nerve and contralateral optic tract to the level of the lateral geniculate nucleus)
DDx:
Opacification of ocular media - cornea, AH, lens, vitreous humour
Retina - chorioretinitis/retinitis, retinal detachment
Optic nerve - optic nerve hypoplasia, neoplasia of optic nerve or compression from neoplasia, infectious or non infectious optic neuritis, retrobulbar abscess/cellulitis, trauma to globe or orbit
Contralateral optic tract to level of lateral geniculate nucleus - hypothalmic/thalmic neoplasia, cerebrovascular accident.
What are the ddx for unilateral abnormal vision with an intact PLR?
PLR intact - suggestive lesion not within portion of visual pathway shared with PLR pathway i.e central portions of visual pathway from contralateral lateral geniculate nucleus to contralateral visual cortex)
Sole neurological finding = focal contralateral forebrain disease
DDX - primary or secondary brain neoplasia, inflammatory/infectious CNS disease, head trauma, cerebrovascular accident.
What are the ddx for bilateral abnormal vision and a PLR deficit?
PLR deficit - peripheral blindness within PLR pathway = up to level of lateral geniculate nucleus
Bilateral ocular medial, bilateral retina, bilateral optic nerve or optic tract up to the level of lateral geniculate nucleus or focal optic chiasm lesion.
DDX:
Bilateral opacification of ocular media
Bilateral retina - SARDS, PRA, retinitis/chorioretinitis, bilateral retinal detachments
Bilateral optic nerves - hypoplasia, infectious/non infectious optic neuritis
Focal optic chiasm - neoplasia, inflammatory/infectious CNS disease, ischaemic necrosis
Optic tracts up to level of lateral geniculate nuclei - neoplasia e.g meningioma, pituatary macroadenoma, inflammatory/infectious CNS disease.
What are the ddx for bilateral abnormal vision with an intact PLR?
Intact PLR + central blindness, lesion affecting portions of visual pathway not shared with PLR (bilateral lateral geniculate nucleus to contralateral visual cortex)
Indicates diffuse/multifocal CNS disease and is often associated with other signs of brain disease e.g forebrain signs (other possibility is can get partial lesions of proximal pathways e.g retina and optic nerve that spare the PLR whilst causing a loss of vision so do assess for other brain signs)
DDX - diffuse/multifocal
Hydrocephalus
Metabolic encephalopathy - hepatic encephalopathy/hypoglycaemia
Inflammatory - granulomatous meningoencephalitis
Infectious - neosporosis, toxoplasmosis, distemper, bacterial CNS disease
Head trauma
Toxins - lead poisoning
Cerebrovascular disease
Space occupying lesions - primary and secondary brain tumours and brain haemorrhage
What is a cerebrovascular disease defined as? What pathological process can cause these?
Any abnormality of the brain as result of a pathological process compromising its blood supply.
Pathological processes:
1. Occlusion via thrombus or embolism
2. Rupture of a blood vessel wall
3. Lesion or altered permeability of the vessel wall
4. Increased viscosity or other changes to the blood
What is the most common form of cerebrovascular disease causing blindness?
Stroke or cerebrovascular accident (CVA)
Sudden onset, non progressive focal brain signs secondary to cerebrovascular disease
> 24hrs of signs to qualify as a stroke - permanent damage to brain
<24hrs = transient ischemic attack (temporary fall in blood supply, signs resolve in 24hrts, no permanent brain damage, mostly embolic disease. Often diagnosed retrospectively)
What are the 2 main pathological causes of a stroke/CVA?
- Ischaemia (with or without infarction) secondary to obstructed vessels
- Haemorrhage caused by rupture of a blood vessel wall.
Define an ischaemic stroke.
Brian relies on permanent supply of oxygen and glucose to maintain ionic pump function.
Lack of perfusion - once at critical levels ischaemia develops sometimes progressing to infarction (tissue death) if it persists long enough.
Infarct = compromised area of brain parenchyma caused by focal occlusion of one or more blood vessels.
Define a haemorrhagic stroke.
Blood leaks from the vessel directly into brain forming haematoma within brain parenchyma or into sub-arachnoid space.
Mass of clotted blood = physical disruption of tissue and pressure on surrounding brain.
Increased intracranial pressure and decreased cerebral blood flow.
Describe the clinical presentation of a cerebrovascular accident (stroke)
What may the fundic examination indicate in patients who have had a CVA?
Peracute/acute onset
Arrest then regression of signs in all except fatal strokes
Worsening of oedema can cause worsening of signs for short period 24-72hrs
Often focal anatomic diagnosis
Neurological deficits dependent on location of stroke
Secondary increased ICP can lead to non specific signs of forebrain, brainstem or cerebellar disturbance.
Fundic exam may show tortuous vessels (systemic hypertension), haemorrhage (coagulopathy/systemic hypertension) or papilloedema (increased ICP)
Which imaging modalities are indicated when assessing a patient for a potential cerebrovascular accident/stroke?
CT and MRI
CT - acute phase of ischaemia, very sensitive for detection of haemorrhagic strokes
MRI - ischaemic stroke within 12-24hrs of the onset of signs, distinguish haemorrhagic lesions from infarction
Functional MRI - improve sensitivity/specificity for diagnosing acute stroke - ideal for identification of hyperacute stroke, can discriminate acute from chronic lesions.
What are the suspected underlying causes for ischaemic strokes?
Thromboemboli (septic, aortic or cardiac)
Atherosclerosis - primary hypothyroidism
Hypertriglyceridemia(Miniature Schnauzers)
Aberrant parasite migration/emboli
Metastatic tumour cells
Intravascular lymphoma
Fibrocartilagenous embolism
Hypertension (CKD, hyperadrenocorticism)
50% concurrent medical condition associated with brain infarcts.
What else should be assessed in an animal diagnosed with an ischaemic stroke?
Blood pressure measurement
Bloods - endocrine disease, CKD, diabetes etc
Assessment of heart (greater risk factor in cats with cardiomyopathy)
Assessment for metastatic disease
Thromboelastography, D-dimer assays and/or antithrombin III evaluation - screening for thromboembolic disease.
What are the underlying triggers for a haemorrhagic stroke?
Rare in dogs compared to people
Congenital vascular abnormalities
Primary and secondary brain tumours
Inflammatory diseases of arteries/veins
Intravascular lymphoma
Brian infarction
Impaired coagulation
Hypertension (cats)
FIP (Cats)
Cerebral amyloid angiopathy (cats)
Intracranial neoplasia
What ancillary diagnostic tests should be considered for a patient who has had a haemorrhagic stroke?
Blood pressure checks
Coagulation profile (prothrombin/activated partial thromboplastin time)
CBC/Biochem
Metastatic disease screening - thoracic/abdo imaging
How do we manage an ischaemic stroke and what is the general prognosis?
No specific treatment - supportive care only
Treat any underlying disease/triggers
Nursing care - holistic patient management
MOST CASES OF ISCHAEMIC STROKE WILL RECOVER IN SEVERAL WEEKS WITH ONLY SUPPORTIVE CARE
Therapeutic target for thrombolytic and neuroprotective therapy = ischemic penumbra
Window of opportunity is approximately 6hrs before irreversible neurological damage occurs.
- Avoid aggressive treatment of hypertension in acute stages unless considerably high >180 as cerebral autoregulation of blood pressure often lost and perfusion to injured areas relies of systemic blood pressure.
- Neuroprotection - prevent excitotoxicity, reduce infarct volume by 30-50%
NDMA antagonists, calcium channel blockers, sodium channel modulators - no efficacy in clinical trials at moment. - Restoration/improvement of cerebral blood flow
Thrombolytic agents but not efficacious/practical in veterinary patients
NO EVIDENCE FOR USE OF GLUCOCORTICOIDS AND INCREASE RISK OF GI COMPLICATIONS AND INFECTION.
ACE inhibitors - enalapril/benazepril or amlodipine
