Muscle Channel Patient Day 2019 Dr Emma Matthews
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Muscle Channel Patient Day 2019
Dr Emma Matthews
The Team• Professor Michael Hanna • Emma Matthews • Doreen Fialho - neurophysiology• Natalie James – clinical nurse specialist• Sarah Holmes - physiotherapy• Richa Sud - genetics• Roope Mannikko – electrophysiology• Iwona Skorupinska – research nurse• Louise Germain – research nurse• Kira Baden- service manager• Jackie Kasoze-Batende– NCG manager• Jean Elliott – NCG senior secretary• Karen Suetterlin, Vino Vivekanandam• – research fellows
What is a skeletal muscle channelopathy?
Muscle and nerves communicate by electrical signals
Electrical signals are made by the movement of positively and negatively charged ions in and out of cells
The ions can only move through dedicated ion channels
If the channel doesn’t work properly, you have a “channelopathy”
Ion channels
• Myotonia congenita – CLCN1
• Paramyotonia congenita – SCN4A
• Hyperkalaemic periodic paralysis – SCN4A
• Hypokalaemic periodic paralysis – 80% CACNA1S
– 10% SCN4A
• Andersen-Tawil Syndrome – KCNJ2
MYOTONIA
PARALYSIS
POTASSIUM CHANNELS
CHLORIDE CHANNELS
SODIUM CHANNELS
CALCIUM CHANNELS
Myotonia and Paralysis
• Two main symptoms
• Paralysis = an inexcitable muscle
– Muscles are very weak or paralysed
• Myotonia = an overexcited muscle
– Muscle keeps contracting and become “stuck”
Muscle action potential
Calcium
Na+
Nav1.4
Ach
Cav1.1 and RYR1
Relaxed muscleMuscle contraction
Ach receptors
Motor nerve
Muscle membrane
T-tubule
Nerve action potential
Motor end plate
+
++
++Cl_ -
-
-
Na+
K+
Myotonia Congenita
• Myotonia = stiff or stuck muscles
• Difficulty starting to move
• “warm up” once I’m moving I’m ok
• Legs>arms or face
• Falls
• +/- Muscle weakness – usually improves with repetition
Paramyotonia Congenita• Myotonia
• COLD!!!
• It gets worse the more I do it
• Eyes + face + hands > legs
• Weakness/paralysis
Periodic Paralysis
• Hypokalaemic
• Night/early morning
• Hours to days
• Carbohydrates
• Hyperkalaemic
• Any time
• Mins to hours
• High potassium foods
POTASSIUM POTASSIUM
Andersen – Tawil Syndrome• Periodic paralysis• Cardiac conduction• Characteristic features
Investigations
• History and Clinical exam
• Blood tests: Potassium, CK, TFTs, Renal tests
• ECG
• Neurophysiology (electrical tests)
• MRI scan
• Genetic tests
EMG Myotonia
EMG - Myotonia Congenita
0
20
40
60
80
100
120
0 10 30 50 70 80 100 120 140 150 170 190 210
Time
CM
AP
am
plid
tue
an
d a
rea
(%
Bas
elin
e)
EMG – Paramyotonia Congenita
0
20
40
60
80
100
120
140
0 10 30 50 70 80 100 120 140 150 170 190 210
Time
CM
AP
am
plid
tue
an
d
area
(%
Bas
elin
e)
EMG – Periodic Paralysis
McManis long exercise test
0
50
100
150
200
0 1 3 5 1 3 5 8 12 16 20 24 28 32 36 40 44CM
AP
Am
plit
ud
e a
nd
Are
a
(% o
f b
asel
ine
)
CMAP amp CMAP area
Treatment
Exacerbating Factors
• Temperature
• Food
• Exercise
Pharmacological Therapies Periodic Paralysis
• Hypokalaemic Periodic Paralysis
– K supplements
– Acetazolamide
– Diuretics: Spirinolactone, Amiloride
• Hyperkalaemic periodic paralysis
– Acetazolamide
– Thiazide diuretics
• Anti-arrhythmic drugs
– Mexiletine
– Flecainide
• Anti-epileptic drugs
– Carbamazepine
– Topiramate, Lamotrigine
Pharmacological Therapies Myotonia
Magnesium
Mexiletine
• Mexiletine is a safe long term treatment for patients with non-dystrophic myotonia
• Patients with chloride channel myotonia may require a higher dose of mexiletine for efficacy.
• Slow dose titration of 100mg per week may help to reduce side effects
• Indigestion therapy may be needed
0
5
10
15
20
25
30
35
40
45
50
% o
f P
atie
nts
Re
po
rtin
g Sy
mp
tom
Acetazolamide
Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors Rev Urol. 2010 Spring-Summer; 12(2-3): e86–e96.
Risk of kidney stones
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