17. Chronic Neurology Flashcards
MS Definition
A chronic inflammatory multifocal, demyelinating disease of the central nervous system of unknown cause, resulting in loss of myelin, and oligodendroglial and axonal pathology
MS Common Symptoms and Signs
Symptoms depend on where in the CNS damage is
Optic neuritis
Motor weakness (with spasticity and hyper-reflexia), pyramidal signs
Sensory disturbances (Paraesthesiae, pain or sensory loss in limbs or trunk)
Fatigue
Lhermitte’s sign (electric shock radiating down back and triggered by neck flexion)
MS other symptoms
Urinary urgency and incontinence
Sexual dysfunction
Dysarthria
Paraesthesiae, pain (incl.trigeminal neuralgia) or numbness of face or tongue
Visual field defect - unilateral, Conjugate eye movement disorders: diplopia, nystagmus
Seizures
Psychiatric disturbances
Vertigo and nystagmus
Impairment of concentration or memory
Hemiparesis
Hemi sensory loss
Ataxic and spastic gait
Impaired coordination, action and intention tremor
Dysmetria
MS Invx
Fundoscopy - eye signs e.g. papillitis. Diplopia, nystagmus, internuclear ophthalmoplegia
Retro-bulbar optic neuritis (2/3)
Optic neuritis with papillitis (1/3)
Multiple Sclerosis Epidemiology
Around 2.5 millions worldwide
Higher prevalence among white people of Nordic origin - ‘Latitude effect’
Highest in UK, Sweden, Denmark
Multiple Sclerosis RF
AI PMHx
HLA-DLRB1*15
VItamin D levels (more sunlight)
Latitude
Multiple Sclerosis MRI
The demyelinated plaques in the white matter of the CNS are the pathological substrate of relapses
Areas of inflammation, with loss of myelin are scattered around the CNS.
The location and size of plaques determine the type and severity of symptoms (given rise to such varied symptoms)
Often plaques are silent, as may be in area of white matter that is of little importance. Or could appear in area of importance like the brainstem, possible leading to respiratory failure.
MS Pathophysiology
During an acute relapse, there is inflammation in response to myelin basic protein. The inflammation leads to demyelination, which causes delay of the nerve impulse and eventually the neurological symptoms. At first these completely resolve (treatment can speed up process- give steroids), but as disease progresses can often be left with residual symptoms.
3 types of MS phenotypes
Relapsing-remitting (RR) - 85%
Patients mostly fine, but suffer from relapses (acute symptoms) which then resolve; for most of these patients this eventually converts to SPMS (mean 10-15 years)
Secondary Progressive MS: gradually more and more disabled, may have more relapses superimposed on this, but often with incomplete recovery.
Primary progressive MS – progressing immediately, without the initial relapsing remitting stage
MS Dx
Clinical - Absence of alternative diagnosis
Dissemination in time (DIT)
Dissemination in space (DIS)
Based off: Clinical history and examination Radiological evidence – MRI Laboratory evidence – CSF Electrophysiology – VEPs
How can we differentiate old and new lesions?
MRI with gadolinium contrast
During an acute attack, inflammation makes the BBB leaky (for 2-6 weeks) to allow immune cells into the CNS (normally brain is immune privileged). GAD also crosses the barrier = lights up any active lesions, and old lesions remain darker
Anything that lights up is at most 6 weeks old.
What is diagnostic of MS in the CSF?
Oligoclonal bands (95% sensitive) present in the CSF but not the serum (B cells release IgG Ab targeting myelin)
NB if present in serum = infection/inflammation systemically
What are VEPs and what are they used for?
Visual evoked potentials (VEPs) – these look for subtle abnormalities in the visual pathways (commonly affected in MS) which may help clinical to pick up subclinical features even the patient was not aware of
A 28 year old Norwegian woman presents to A&E after she was unable to fell the hot water on her left leg whilst taking a bath. CSF analysis demonstrated oligoclonal bands that were unmatched with the serum. Which of the following would most likely confirm a diagnosis of Multiple Sclerosis?
Multiple lesions on MRI that all enhanced with gadolinium
The patient’s symptoms reoccur 1 year later
The patient develops blurry vision in one eye a year later
The patient reports blurry vision currently
A 1 year follow up finds oligoclonal bands matched with the serum
Risk factors of being young, Nordic woman. Also demyelination can be precipitated by a hot bath
DIT
DIS
A 40 year old woman visits her GP complaining of tiredness. On questioning, she reports getting tired when climbing the stairs or during a conversation. She often has to stop what she is doing to regain her energy. The GP asks her to look upwards, and after a few seconds she begins to develop ptosis. What is the most likely diagnosis?
Iron Deficiency Anaemia Myasthenia Gravis Lambert Eaton Myasthenic Syndrome Carcinoma Horner’s Syndrome
This question demonstrates the classical presentation of myasthenia gravis – muscles fatiguing after use. Also a 40 year old woman which is typical group of people affected.
If it were not for the final sentence then IDA would be most likely statistically, but it wouldn’t produce the stereotypical ptosis on upwards gaze.
LEMS would be tiring at first and improve with use, so wrong way around for this question.
Carcinoma can obviously lead to tiredness, but firstly it is a little vague and secondly wouldn’t give the ptosis after a few seconds, likely provide some other symptoms too.
Horner’s syndrome is characterised by ptosis, but that is at rest.
Myasthenia Gravis Symptoms and signs
Symptoms - Muscles fatigue with use Ptosis Diplopia Dysarthria Dysphagia ±SOB
Signs
Fatigable muscles
Normal reflexes
Who does MG normally affect
It most commonly impacts young adult women (under 40) and older men (over 60) – as it is an autoimmune condition
What muscles does MG usually implicate
Those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing
Muscles that control breathing and neck and limb movements may also be affected.
MG Aetiology
Antibodies block, alter, or destroy nAChR or MuSK
May also have seronegative myasthenia
Muscles will fatigue with repeated use as more and more ACh is required to maintain contraction; in MG this happens quicker compared to normal person
MG Associations
Thymic hyperplasia (70%) Thymoma (10%)
Mg Investigations
Bloods – anti-AChR or anti-MuSK
EMG -demonstrate muscle weakness, action potentials will gradually decrease over time
CT/MRI - for thymomas
Lambert Eaton Myasthenic Syndrome Symptoms
Symptoms – weakness where muscles improve with use
Difficulty walking (upper legs and hips)
Weakness in upper arms and shoulders
Similar symptoms to myasthenia gravis - mild weakness in eye, talking + chewing muscles etc
Autonomic: Dry mouth, constipation, incontinence
Signs
Muscles function better following use
Hyporeflexia
Lambert Eaton Myasthenic Syndrome Aetiology
Anti voltage gated calcium channels on nerve endings that are required to trigger exocytosis of Ach –> less Ach cannot cause normal contractions
Improves with repeated use as incoming stimulus leads to cumulative opening of the few calcium channels not blocked by antibodies
Lambert Eaton Myasthenic Syndrome Associations
Small cell lung cancer (paraneoplastic - producing Ab); older age of onset (averaging 60 years) and is caused by an accidental attack of the nerve terminal by the immune system as it attempts to fight the cancer. Tx of cancer removes LEMS
Autoimmune disease (onset = 35)
Lambert Eaton Myasthenic Syndrome Investigations
Bloods - Antibodies to voltage-gated calcium channels (VGCCs) have been reported in 75-100% of LEMS patients who have small cell lung cancer (SCLC) and in 50-90% of LEMS patients who do not have underlying cancer.
EMG
CT/MRI - lung cancer?
A 50 year old man visits his GP complaining of weakness in his right arm. He reports the weakness has gradually developed over the last 2 months. On inspection, the GP notices wasting of his tongue and hyperreflexia. His right arm is rigid. What is the most likely diagnosis?
Stroke Multiple Sclerosis Parkinson’s disease Motor Neuron Disease Carpel Tunnel Syndrome
Motor Neuron Disease
The key thing is spotting the mixture of UMN (hyperreflexia and rigidity) and LMN signs (wasting).
Men are more likely to get MND
Stroke would be an acute onset, not progressive. MS would not really give wasting as it involved UMN’s, would also most likely be an acute attack.
Parkinson’s does have motor signs, but doesn’t give wasting as again it’s CNS not PNS. Also missing the classic triad.
Carpel tunnel syndrome can give arm/hand weakness, but no signs/symptoms outside of this.
MND Definition and Incidence
5-8/100,000
(AML/Charcot’s Disease)
Chronic neurodegenerative condition (hardening of the lateral corticospinal tracts) causing progressive muscle wasting, paralysis and death usually within 3-5 years due to respiratory failure
Progressive denervation and secondary muscle weakness of limbs, trunk, tongue and respiratory(Intercostal) muscles. Onset usually occurs in distal muscles of a single limb or may be bulbar, followed by widespread progression
MND Symptoms
Bulbar symptoms - dysphagia, impaired speech
Spastic weakness/paralysis of all skeletal musc –> respiratory failure
SOB
Changed cognitive function (15%)
Sparing of oculomotor, sensory and autonomic function (bladder, bowel, sexual function preserved)
Signs of MND
Wasting of:
- Thenar hand muscles (base of the thumb
- Tongue (bulbar onset)
What does bulbar mean?
Relating to the medulla oblongata (it’s shaped like a bulb)
