CRF clinics: non-MND Flashcards
Stiff person syndrome (SPS)
a) My presentation
b) Common features
c) Antibody, and positivity
d) Diagnostic criteria
e) Common differentials
f) Management
a) - Truncal stiffness - “like a plank”, could not bend in the middle
b) - Truncal stiffness
- Limb stiffness
- Spasms, may be triggered by startling
- Severe spasms can cause dyspnoea, tachycardia –> status spasticus
- A third have autoimmune disease like T1DM
- Cerebellar signs in 15% - dysarthria, ataxia, etc.
c) Anti-GAD. Should be very high. 20% seronegative, in this case do CSF anti-GAD. If this negative, need to go through all the others.
d) 1. stiffness of the axial muscles, especially abdominal and thoracolumbar paraspinals, leading to hyperlordosis
2. superimposed painful spasms triggered by anxiety, tactile or auditory stimuli;
3. electromyographic evidence of continuous motor unit activity of agonist and antagonist muscles;
4. high-titre GAD antibodies with the cut-off positivity titres > 10.000 IU/ml by ELISA. In patients with suspected SPS-SD but with anti- GAD antibody-titre lower than 10,000, a spinal tap is necessary to assess GAD positivity in 5. absence of other neurological findings that may suggest an alternative diagnosis.
e) - ALS (may mimic PLS)
- Dopa responsive dystonia, other Parkinsonism/PD
- HSP
- MS
- Functional
f) - Symptomatic - diazepam, baclofen, gabapentin, Botox, physiotherapy
- If still symptomatic, trial IVIG, then rituximab, then HSCT (PLEX and steroids generally ineffective)
Parkinsonian examination*.
a) Bradykinesia - movements, what to look for
b) Rigidity - vs spasticity, where most sensitive, activation manoeuvres, cogwheeling
c) Tremor - position, testing tremor types
d) Gait and balance - assessment, normal gait vs PD gait
a) - Tap index finger and thumb as big and fast as they can for 10 reps.
- If struggles with this, fist open and close instead, or supinate/pronate
- Toe tap for lower limbs
Look for reduction in amplitude and velocity
b) - Not velocity- or direction-dependent (same with flexion and extension) unlike spasticity
- Hold weight of the forearm to relax the arm
- Most sensitive at wrist - roll wrist and then do wrist flexion/extension
- Also try at elbow flexion/extension and pronation/supination
Activation manoeuvres - tapping the opposite hand on the opposite thigh while testing for rigidity can bring it out
- Cogwheeling is rigidity with tremor superimposed (so if patient does not have tremor they won’t have cogwheeling)
c) - Rest tremor most sensitive by resting hands on ulnar side on their thighs (not flat on thighs), and observe while distracted
- Postural tremor - hands outstretched
- Action (kinetic) tremor - Finger/nose. Moving object to test for ataxia
PD patients should have more resting tremor vs postural/kinetic tremor
d) Balance
- assess getting out of chair with arms across chest in one movement
- Pull test - can they correct balance in 1-2 steps? (do it with wall behind you and coach patient beforehand)
Gait
- Normal gait involves normal arm swing, heel strike, stride length and turning
- PD gait involves reduced arm swing and heel strike, reduced stride length and difficulty turning
Myotonia congenita
a) What is it?
b) clinical features
c) treatment
a) In Myotonia Congenita, the Chloride channels in muscles are not working properly, due to a mutation in the CLCN1 gene - can be autosomal dominant or recessive
b) - Myotonia (impaired relaxation of muscles after activation)
- muscle cramps/pain/ stiffness
- triggers: after sitting still for a while, on exercise, cold weather, stress
c) Mexiletine (namuscla) - sodium channel blocker which works as an antiarrhythmic and a muscle relaxant
Inclusion body myositis (IBM)
a) What is it?
b) Pattern of weakness
c) Investigations
d) Management
a) Slowly progressive degenerative muscle wasting disease.
Characterised by muscle biopsy showing ‘inclusion bodies’ - rimmed vacuoles in muscle tissue
b) Asymmetrical weakness, classically finger flexors and knee extensors (quads)
- medial forearm wasting
- can sometimes cause bulbar weakness
- more slowly progressive than MND
c) - Raised CK (>1000)
- EMG
- Muscle biopsy
d) Supportive
- Steroids generally ineffective
Myasthenia gravis: assessment, diagnosis and investigations
a) 1st line diagnostic tests
b) classification subtypes
a) - Serum AChR antibody (followed by serum MuSK if AChR negative)
- TFTs
- Neurophysiology - repetitive nerve stimulation (followed by single fibre EMG if negative)
- CT thorax for thymoma
- MR brain if any ambiguity to r/o SOL
- Tensilon test if diagnostic doubt
b) - Ocular/generalised
- AChR or MuSK seropositive/negative
- Thymoma/no thymoma
- Congenital myasthenia
c)
Myasthenia gravis: treatment
a) Choosing OP vs IP care
b) Who to do thymectomy in?
c) Pyridostigmine dose titration
d) Prevention of pyridostigmine SEs
e) Steroid dose titration
f) Clinical remission on steroids
Guidelines from Sussman et al (BMJ):
https://pn.bmj.com/content/15/3/199
a) Indications for inpatient care
- Respiratory involvement
- Significant bulbar involvement
- Progressive severe limb weakness
b) - Thymoma present
- Consider at presentation if AChR positive and aged under 45
c) - Initially 30 mg (½ tablet) QDS for 2–4 days
- Then 60 mg (1 tablet) QDS for 5 days
- Then 90 mg QDS over 1 week if required
- The duration of action varies, and some patients require five divided daily doses.
If pyridostigmine does not control symptoms satisfactorily within a few weeks, start prednisolone
- When weaning, withdraw slowly at 30–60 mg per week until lowest effective dose or total withdrawal
d) Propantheline or mebeverine, to reduce procholinergic SEs like diarrhoea/ abdo cramps/ hypersalivation
e) If pyridostigmine does not effectively control MG, start prednisolone (after a few weeks or less)
Ocular MG:
- Start 5 mg on alternate days for three doses and increase by 5 mg every three doses until symptoms improve.
- The maximum dose is 50 mg on alternate days
Generalised MG:
- Start 10 mg on alternate days for three doses and increase by 10 mg every three doses until symptoms improve.
- Maximum dose is 100 mg alternate days
- It may take many months to achieve full remission.
f) Absence of symptoms and signs having withdrawn pyridostigmine. Steroids should only be weaned down once this has been achieved
MG management: continued
a) When to consider immunosuppression above steroids?
b) Which drugs to try?
c) Relapsing myasthenia - causes
d) Relapsing myasthenia - management
a) - Where lowest effective prednisolone dose on weaning higher than 7.5–10 mg/day (15-20mg alternate days), indicates need for azathioprine
b) - Azathioprine first line (check TPMT levels first - if severe deficiency then to avoid)
- Slow to achieve maximum effect - can take around 2 years
- Alternatives include MMF, methotrexate and ciclosporin (consider teratogenic risk of MMF in females and MTX in males and females)
c) - Drug reduction
- Infection
- Medications given that are CI in MG - beta-blockers,
d) - Resume steroid escalation as per normal protocol
- Add AZT if the steroid dose is already >15-20mg on alternate days
Parkinson’s stages
a) Preclinical / early features
a) - Genetic risks
- Hyposmia
- REM sleep behaviour disorder
Spinal muscular atrophy.
a) What is it?
b) Presentation, classification and progression
c) Management
a) - A genetic neuromuscular disease that is the leading genetic cause of infant mortality, affecting 1 in 6,000 live births
- Autosomal recessive and caused by mutations in the survival motor neuron 1 (SMN1) gene on Ch 5q13
- Leads to defective SMN protein, which is involved in pre-mRNA splicing
- results in alpha- motor neuron deterioration in the brainstem/spinal cord
b) Classification types 1-4 based on severity related to amount of functional SMN protein:
- Type 1 - onset 0-6 months
- Type 2 - early childhood
- Type 3 - late childhood/adolescence
- Type 4 - adult onset, often live normal life
Leads to limb and respiratory muscle weakness
Note - most have type 1 and 50% die before the age of 2
c) Zolgensma:
- Gene replacement therapy. Delivers functional SMN1 gene via AAV-9 vector to lead to functional SMN protein
- It does not integrate with the host DNA but remains separate
- It is given as a one-off intravenous infusion
Nusinersen (Spinraza):
- ASO therapy that binds to the pre-mRNA of the SMN2 gene
- Due to splicing, SMN2 produces a truncated and less functional version of the SMN protein
- Nusinersen affects this splicing to include exon 7 in SMN2 and produce a more functional SMN protein
- It is given as regular intrathecal injections
Baclofen
a) weaning.
b) alternatives for spasticity
a) 5mg every 3 days.
b) Tinazidine
Botox
Post-polio syndrome
a) What is it and when it develops
b) Presentation
a) Acute polio infections that cause some neuromuscular weakness, then a period of stability/improvement, followed by post-polio syndrome around 15 years or more later, with worsening or new neurological weakness
- Affects the anterior horn cells
b) 15 years or more following polio infection
- LMN weakness of limbs, wasting, pain, fasciculations
- Gradual onset and slow progress
- can less commonly involve bulbar and respiratory muscles
Ulnar claw
a) What is it?
b) What surgery can be done for ulnar nerve compression?
Inability to extend the 4th/5th digits due to ulnar pathology
(as opposed to hand of benediction which is median pathology causing inability to flex 2nd/3rd digits)
b) Ulnar nerve transposition
- moves ulnar nerve from behind medial epicondyle to prevent irritation/compression here
Reflexes
a) frontal release signs
b) DTRs and nerve roots
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075597/
https://m.youtube.com/watch?v=Fz4kAa4Wj_g&feature=youtu.be
a) Palmomental, glabellar, snout, rooting
b) Supinator - C5-6 (brachioradialis)
Biceps - C5-6 (musculocutaneous)
Pectoralis - C5-T1 (medial and lateral pectoral nerves)
Triceps - C7-8 (radial)
Knee - L3-4
Ankle - S1
Crossed adductors
Hoffmann
Babinkski
Peripheral neuropathy: small-fibre vs large-fibre
a) Tracts affected
b) Symptoms
c) O/E
d) EMG
e) Causes
Small fibre:
- A-delta and C-fibres, controlling pain/temperature
- No motor features
- Pain more common
- May have autonomic symptoms
- Loss of pain/temp on examination
- Ankle jerks normal
- EMG normal
Large fibre:
- A-alpha fibres controlling light touch, vibration, proprioception
- May have some motor involvement
- Pain less prominent
- Loss of vibration/light touch, later will lose proprioception and have sensory ataxia
- Ankle jerks absent
- May have wasting
- EMG abnormal
Peripheral neuropathy: screening tests
a) Bloods
b) Other
a) - FBC, U&E, LFT, bone profile
- CRP/ESR, ?vasculitis screen
- HbA1c (high in 20%)
- B12/folate/vitamin D
- Myeloma screen (high in 5%)
- Infection screen - Lyme, HIV, (not syphilis)
- ?genetic screen for CMT
b) - Urine Bence Jones protein if paraproteinaemia
- NCS/EMG
- Usually don’t require imaging unless concern for lumbar radiculopathy
