Neuromyelitis optica; Holmes-Adie pupil; Chronic Fatigue Syndrome Flashcards
Describe what is meant by Neuromyelitis optica (NMO) [1]
Neuromyelitis optica (NMO), also known as Devic’s disease, describes a spectrum of rare autoimmune demyelinating CNS conditions.
What is the pathophysiology of NMO [+]
NMO predominately affects the optic nerve and spinal cord and most cases follow a relapsing pattern (80-90%) compared to a monophasic pattern. It can occur at any age and occurs more frequently in women.
- It is believed that most cases of NMO occur due to IgG Antibodies to Aquaporin-4 (AQP4-Abs)
- Aquaporin 4 is a water channel protein highly expressed in the body and can be located in the brain, spinal cord, and optic nerves.
- Peripheral production of AQP4-Abs leads to demyelination, axonal loss and perivascular lymphocytic –> presents as optic neuritis and/or transverse myelitis
NB: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG), are also seen in NMO, particularly in the non-relapsing variant.
Describe the common features of NMO [5+]
Optic neuritis
* May be bilateral, unilateral or sequential
* Eye pain, typically worse with movement
* Visual loss (more severe than in multiple sclerosis)
Transverse myelitis
* Limb weakness- symmetric paraparesis or quadriparesis
* Bladder dysfunction
* Sensory loss-below the level of the spinal cord lesion
* Paroxysmal tonic spasms-affects the trunk or limbs
* Radicular pain
Brainstem syndromes
* Area postrema (located on the floor of the 4th ventricle) lesions-intractable hiccups, nausea, or vomiting
Pruritus
* Caused by inflammation of fibres in the spinothalamic tract
Pain
* Very common symptom (80% of attacks)
* Involving the eye in cases with optic neuritis
* Involving the trunk or legs in cases transverse myelitis
What is the hallmark presentation of NMO? [1]
In general, the hallmark presentation of NMO is of attacks of optic neuritis and/or transverse myelitis.
A 2015 neurology international consensus agreed that diagnosis should be made on the following criteria [3]
A 2015 neurology international consensus agreed that diagnosis should be made on the following criteria:
* At least 1 core clinical characteristic
* Positive Aquaporin 4-Antibodies
* Alternative diagnosis exclusion
Investigations done usually for NMO and to exclude other diagnoses include [5]
Lumbar puncture
- CSF oligoclonal bodies-absent
MRI Head
- Often done to differentiate from Multiple sclerosis
- Most often normal; demyelinating lesions may be found
MRI of the spinal cord-longitudinal and central cord lesions
* >/= 3 contiguous vertebral segment lesions
MRI of the optic nerve
* Longitudinal Lesion
Bloods:
* Aquaporin 4-antibodies & Anti-MOG (myelin oligodendrocyte glycoprotein) antibodies
What are the core clinical characteristics of NMO? [6]
Optic neuritis
Area postrema syndrome
Myelitis
Brainstem syndrome
Narcolepsy or acute diencephalic syndrome
* Present with diencephalic MRI lesions
Cerebral syndrome
* Present with diencephalic MRI lesions
How do you differentiate NMO from MS (similarities vs differences) [3]
Similarities:
- Both have relapsing courses, both can feature optic neuritis and/or transverse myelitis, both respond to similar treatment including corticosteroids
Differences:
- Multiple sclerosis can affect regions outside of the optic nerves and spinal cord where as NMO rarely does,
- Lumbar puncture is normal usually in NMO
- MRI of the head is often normal
What are the main aims of treatment of NMO? [2]
The main aims of treatment are;
* To reduce the frequency of attacks
* To reduce the severity of attacks when they do occur
How do you treat NMO acutely?
Acute attacks
Corticosteroids
* 1st Intravenous Methylprednisolone for 5 days
* 2nd Oral prednisolone tapered over weeks to months
Plasma exchange therapy (PLEX)
* If unresponsive to corticosteroids
* Usually for 5 cycles
What is the long term prophylaxis and remission treatment for NMO?
Long-term immunotherapy is recommended to incept as soon as a diagnosis is made. There is a lack of guidelines on a set regimen but a host of drugs have been shown to be effective in sustaining remission.
Corticosteroids; Oral prednisolone should be given alongside other immunosuppressives drugs
Azathioprine; Around 70% reduction in relapses
Mycophenolate mofetil; Around 80% reduction in relapses
Monoclonal antibodies
* Options include Eculizumab, Rituximab and Satralizumab.
* In the UK used as second line treatment; they are not used first line mainly owing to cost.
What are possible complications of NMO? [6]
complications may be related to optic neuritis, transverse myelitis and the other features of an NMO acute attack. Examples include
* Vision loss from optic neuritis
* Erectile dysfunction from transverse myelitis
* Paralysis or paraplegia from transverse myelitis
Complications may occur as a result of treatment, including;
* Osteoporosis from steroid use
* Agranulocytosis from monoclonal antibody, azathioprine or mycophenolate use
NMO is associated with as significant mental health burden, with cases of anxiety and depression noted among patient.
Describe what is meant by Holmes-Adie pupil [1]
What causes this condition [1]
Holmes-Adie pupil is a neurological condition characterized by an enlarged pupil that reacts slowly to light and near stimuli
- The exact cause of Holmes-Adie pupil is unknown, but it is believed to be related to damage or degeneration of the ciliary ganglion or its nerve supply which has parasympathetic fibers responsible for pupillary constriction and accommodation.
Describe the clinical features of Holmes-Adie pupil [6+]
Anisocoria:
- Patients with Holmes-Adie pupil commonly present with anisocoria, i.e., unequal size of pupils.
- The affected pupil appears dilated in comparison to the contralateral side.
Tonic Pupillary Response:
- The hallmark feature of this condition is the tonic response observed upon direct light stimulation. When exposed to light, the affected pupil demonstrates slow and prolonged constriction followed by gradual redilation.
- This sluggish reaction is best appreciated when comparing it to the normal brisk constriction of the unaffected side.
Light-Near Dissociation:
- Another characteristic feature is light-near dissociation, where there is a reduced or absent pupillary reaction to light while maintaining a relatively preserved response to near stimulus (accommodation).
- This phenomenon occurs due to the selective involvement of parasympathetic fibres innervating the iris sphincter muscle.
Vermiform Movements:
- Upon close examination of the affected iris under slit-lamp biomicroscopy, one may observe irregular, undulating movements known as vermiform movements. These subtle movements are attributed to segmental denervation and reinnervation of iris sphincter muscle fibres.
Accommodative Dysfunction
- Patients may report difficulty focusing on near objects or experience blurred vision at near distances due to impaired accommodation reflex.
Associated Neurological Findings:
- Holmes-Adie syndrome, a variant of this condition, is characterized by the presence of additional neurological findings such as areflexia or hyporeflexia, particularly in the lower extremities. This manifestation results from damage to the peripheral nerve fibres that supply the muscle spindle stretch receptors.
What is meant by chronic fatigue syndrome? [1]
Characterized by persistent fatigue that is not relieved by rest, and often accompanied by other symptoms such as muscle pain, headaches, and cognitive impairment.
Describe the diagnostic criteria for chronic fatigue syndrome
The diagnosis of CFS is primarily based on clinical presentation and exclusion of other potential causes of fatigue. According to the Institute of Medicine (IOM) criteria from 2015, a diagnosis of CFS requires the following three core symptoms:
- 1. Substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social or personal activities that persists for more than six months and is accompanied by fatigue.
- 2. Post-exertional malaise (PEM), defined as worsening of symptoms following physical or mental exertion.
- 3. Unrefreshing sleep despite adequate hours spent asleep.
dditionally, at least one of the two following symptoms must be present:
- 4. Cognitive impairment affecting attention, memory, information processing speed or executive function.
- 5. Orthostatic intolerance manifested by lightheadedness, dizziness or fainting upon standing up.
NICE recommend that we suspect CFS if: [3]
- the person has had all of the persistent symptoms for a minimum of 6 weeks in adults and 4 weeks in children and young people and
- the person’s ability to engage in occupational, educational, social or personal activities is significantly reduced from pre-illness levels and
- symptoms are not explained by another condition.
A diagnosis of CFS should be made if which symptoms are present for 3 months [6]
All of these symptoms should be present:
Debilitating fatigue that is worsened by activity, is not caused by excessive cognitive, physical, emotional or social exertion, and is not significantly relieved by rest.
Post-exertional malaise after activity in which the worsening of symptoms:
* is often delayed in onset by hours or days
* is disproportionate to the activity
* has a prolonged recovery time that may last hours, days, weeks or longer.
Unrefreshing sleep or sleep disturbance (or both), which may include:
* feeling exhausted, feeling flu-like and stiff on waking
* broken or shallow sleep, altered sleep pattern or hypersomnia.
Cognitive difficulties (sometimes described as ‘brain fog’), which may include problems finding words or numbers, difficulty in speaking, slowed responsiveness, short-term memory problems, and difficulty concentrating or multitasking.
Describe the management for CFS [4]
refer to a specialist CFS service if the diagnostic criteria are met and symptoms have persisted for 3 months
energy management
* a self-management strategy that involves a person with ME/CFS managing their activities to stay within their energy limit, with support from a healthcare professional
physical activity and exercise
* do not advise people with ME/CFS to undertake exercise that is not part of a programme overseen by an ME/CFS specialist team
* should only be recommended if patients ‘feel ready to progress their physical activity beyond their current activities of daily living’
* graded exercise therapy used to be recommended but is now specifically not recommended by NICE
cognitive behavioural therapy
* NICE stress this is ‘supportive’ rather than curative for CFS
