Chronic inflammatory demyelinating polyneuropathy (CIDP); Creutzfeldt-Jakob disease (CJD); narcolepsy Flashcards
Describe what is meant by Chronic inflammatory demyelinating polyneuropathy (CIDP)
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive polyneuropathy. The underlying cause is not fully understood, but involves a deranged immune response causing peripheral nerve myelin damage and CIDP is thus classed as an autoimmune disorder
What are the key stages of pathophysiology of CIDP [3]
Although not yet fully defined, it is thought that it results from cell-mediated and humoural mechanisms. Inflammatory CD4 and CD8 T cells and autoantibodies to myelin proteins are thought to be key mediators of the attack on peripheral nerve tissue.
A key step is the breakdown of the blood-nerve barrier allowing attack on the endoneurium.
The resulting inflammatory lesions affecting peripheral myelin in combination with proposed auto-antibody binding to nodes of Ranvier cause the electrophysiological deficits observed and the clinical symptoms.
What are the clinical features of CIDP? [3]
No definitive clinical criteria have been described, and diagnosis is based on the constellation of typical clinical signs and electrophysiological test results.
The European Federation of Neurological Societies describe typical CIDP
- as a ‘chronically progressive, step-wise, or recurrent symmetrical proximal and distal weakness and sensory dysfunction of all extremities, developing over at least 2 months (cranial nerves may be affected), and absent or reduced tendon reflexes in all extremities.’
This is accompanied by supportive electrodiagnostic criteria for typical CIDP which include:
* More than 50% prolongation of motor distal latency above upper limit of normal (ULN) in 2 nerves
* More than 30% reduction of motor conduction velocity below the lower limit of normal (LLN) in 2 nerves
NB: 50% of patients present with typical CIDP (motor and sensory symptoms), whilst 5-35% have sensory-predominant CIDP, and 7-10% present with motor-dominant CIDP.
Which Ix findings would support CIDP?
Sensory and motor nerve conduction studies, performed bilaterally
* Electrodiagnostic test results form a key part of diagnostic criteria
Lumbar puncture, including cytology and protein analysis
* Elevated CSF protein with leukocyte count < 10/mm3 supports the diagnosis of CIDP
MR imaging
* Gadolinium enhancement and/or hypertrophy of the cauda equina, lumbosacral or cervical nerve roots, or the brachial or lumbosacral plexuses supports CIDP diagnosis.
Nerve biopsy
* Evidence of demyelination and/or remyelination by electron microscopy of nerve biopsy supports CIDP diagnosis
Tx fpr CIDP? [5]
Guidelines suggest that patients with confirmed CIDP whose symptoms are mild or do not interfere with activities of daily living may be observed without treatment initially.
In those requiring treatment:
Corticosteroids
* 60mg OD oral prednisolone for 6 weeks recommended as first line
Plasma exchange
* Effective for quick relief of symptoms, but requires combining with other treatments to demonstrate longer term benefits.
Intravenous immunoglobulin (IVIG)
* A Cochrane systematic review concluded that IVIG improves symptoms for at least 2-6 weeks compared with placebo, with one trial demonstrating benefits up to 48 weeks.
Analgesia for neuropathic pain
* Some patients may require analgesia e.g. gabapentin, pregabalin for neuropathic pain if this contributes a significant part of their symptoms.
Describe what is meant by Creutzfeldt-Jakob disease (CJD) [1] and basic pathophysiology [2]
A rapidly progressive neurological condition caused by prion proteins. – These proteins induce the formation of amyloid folds resulting in tightly packed beta-pleated sheets resistant to proteases.
What are the features of CJD? [2]
What Ix would you use to dx? [3]
Features
* dementia (rapid onset)
* myoclonus
Investigation
* CSF is usually normal
* EEG: biphasic, high amplitude sharp waves (only in sporadic CJD)
* MRI: hyperintense signals in the basal ganglia and thalamus
What is the diference in presentation of sporadic [3] and new variant CJD?
Sporadic CJD
* accounts for 85% of cases
* 10-15% of cases are familial
* mean age of onset is 65 years
New variant CJD
* younger patients (average age of onset = 25 years)
* psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting features
* the ‘prion protein’ is encoded on chromosome 20 - it’s role is not yet understood
* methionine homozygosity at codon 129 of the prion protein is a risk factor for developing CJD - all patients who have so far died have had this
* median survival = 13 months
a 65-year-old man is investigated for rapid onset memory problems. On examination he is noted to have cerebellar signs and myoclonic jerks
Define transverse myelitis [1]
Transverse myelitis is a rare neuro-immune condition that causes focal inflammation of the spinal cord.
- typical patient presents with acute or subacute symptoms below the level of the lesion, including sensory impairment, motor weakness and bladder or bowel dysfunction
Describe the pathophysiology of transverse myelitis [+]
PM:
Due to the diverse spectrum of transverse myelitis, the pathophysiology greatly depends on the underlying cause.
* This heterogeneity and the involvement of both white and grey matter means that transverse myelitis is classed as a mixed inflammatory disorder.
* Inflammation affects myelin, oligodendrocytes, neurons and axons.
* In the majority of cases, there is perivascular infiltration by lymphocytes and monocytes in the spinal cord lesion.
* This is accompanied by axonal degeneration.
Osmosis:
- Inflammation of spinal cord across whole segment or segments
- Most commonly in thoracic region
- Inflammation might be caused by infection, MS, or idiopathic
- Pathogens - mycoplasma pneumonia; HSV or dengue; schistosomiasis
- causes damage to myelin in spinal cord causing messages up and down spine fail to be delivered
NB: Spinal cord - grey matter (middle): cell bodies; white matter - myelinated neurons
What are the three main tracts of spinal cord (and functions) [3]
Corticospinal tract (descending pathway)
- Motor from brain to muscles
- voluntary muscle movement
Dorsal column: (ascending pathway)
- sensory: pressure, vibration, fine touch and prioprioception
Spinothalamic: ascending pathway
- lateral tract: pain; pressure and temp
- anterior tract: crude touch (cant localise)
Describe the presentation of transverse myelitis [+]
Depends on the track damaged
Usually a well defined sensory level (sensory loss below this level) but also motor and autonomic dysfunction
If corticospinal tract:
- weakness and problems with voluntary muscle movement below level
If spinothalamic:
- loss of temp and pain sensation
Dorso-column:
- Problems with balance and spatial orientation
PM:
- The most common first symptom is sensory change (39%), weakness (25%) and pain (22%) with autonomic dysfunction in the form of bladder and bowel symptoms being less frequent first symptoms.
Motor symptoms (80%)
* Weakness of lower or all extremities (depending on the level of the lesion)
* Hyperreflexia
* Spasticity
* Very acute cases may initially present with flaccidity and absence of reflexes due to spinal shock
Sensory symptoms (75%)
* Pain
* Paraesthesia
* Dysaesthesia (unpleasant sensation upon touch)
Autonomic symptoms (60%)
* Urinary frequency, urgency and retention
* Bladder and bowl incontinence
* Sexual dysfunction
Describe how you dx transverse myelitis
PM:
The diagnostic criteria of transverse myelitis rely on the presence of motor, sensory and/or autonomic dysfunction localised to a spinal cord segment, in the absence of spinal cord compression.
- Investigations are used to rule out compression and then to find the underlying cause.
Investigations
MRI spinal cord with and without gadolinium
* To exclude spinal cord compression and confirm inflammation
* In transverse myelitis, the cord appears swollen with gadolinium enhancement of the lesion
Lumbar puncture
* To confirm the inflammation
* CSF analysis for cell count, cell differential, protein level, IgG index and oligoclonal bands
* Abnormal in approximately half of the patients with transverse myelitis.
Tx of TM? [2]
Acute management
* IV methylprednisolone once a day for 3-5 days
* For patients not responding to glucocorticoids: plasmapheresis of 1.1 to 1.5 plasma volumes exchanged, once every two days for ten days.
Supportive care
* Patients with cervical transverse myelitis may need critical care team involvement due to a risk of neurogenic respiratory failure.
* Acute urinary retention is managed by catheterization.
* Deep vein thrombosis prophylaxis
* Acute rehabilitation which includes passive and active physiotherapy to maintain range of movement, manage spasms and decrease the risk of contractures.
patients who develop acute complete transverse myelitis have at least a 5-10% chance of developing []
Multiple sclerosis: patients who develop acute complete transverse myelitis have at least a 5-10% chance of developing multiple sclerosis.
Describe what is meant by narcolepsy [+]
Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis.
What causes narcolepsy? [1]
It is caused by the loss of hypocretin-producing neurons in the hypothalamus, which regulate wakefulness and sleep.
Describe the clinical features of narcolepsy [4+]
Features
* typical onset in teenage years
* hypersomnolence
* cataplexy (sudden loss of muscle tone often triggered by emotion; without LOC)
* sleep paralysis
* vivid hallucinations on going to sleep or waking up
Tx of narcolepsy? [3]
Treatment options include stimulants to improve wakefulness
- modafinil
antidepressants to reduce cataplexy and other symptoms
sodium oxybate
- to improve nighttime sleep and reduce daytime sleepines
