7. Hyperkalemic Periodic Paralysis
• term hyperkalemic is misleading since patients
are often normokalemic during attacks.
• Onset first decade
• M : F 1:1
• Attacks are brief and mild, usually lasting 30
minutes to 4 hours.
• Weakness affects proximal muscles, sparing
bulbar muscles.
• Attacks are precipitated by rest following exercise
and fasting.
8. • In a variant of this disorder, the predominant
symptom is myotonia without weakness
(potassium-aggravated myotonia).
• The symptoms are aggravated by cold, and
myotonia makes the muscles stiff and painful.
• Clinically apparent myotonia is seen less than
20% of patients, but electrical myotonia may
be found in 50-75%.
9. Pathophysiology
In hyperKPP, Na+ channels fail to inactivate and
prolonged openings and depolarization result.
Increased extracellular K+ levels worsen the
inactivation of Na+ channels
10. INVESTIGATIONS
• Potassium may be slightly elevated but may also
be normal during an attack.
• NCV reduced motor amplitudes and In between
attacks of weakness, the conduction studies are
normal.
• EMG may be silent in very weak muscles.
• often demonstrate myotonic discharges during
and between attacks.
• Muscle biopsy shows vacuoles that are smaller,
less numerous, and more peripheral compared to
the hypokalemic form or tubular aggregates.
11. TREATMENT
• For patients with
frequent attacks,
acetazolamide (125–
1000 mg/d) is helpful.
• mexiletine is helpful in
patients with significant
myotonia.
12. HYPOKALEMIC HYPERKALEMIC
PREVELANCE 1:100,000 1:200,000
AGE OF ONSET FIRST AND SECOND
DECADE OF LIFE
FIRST DECADE
SYMPTOMS
DURING ATTACKS
ACUTE ONSELT
FLACCID PARALYSIS
PROXIMAL >>>
DISTAL
WEAKNESS OF
PROXIMAL
MUSCLE,SPARING
BULBAR MUSCLE
SYMPTOMS
BETWEEN ATTACKS
ASYMPTOMATIC ASYMPTOMATIC
FREQUENCY Daily to yearly May be 2–3/d
DURATION 2–12 h From 1–2 h to >1 d
13. HYPOKALEMIC HYPERKALEMIC
Effect of muscle
cooling
No change Increased myotonia
TRIGGERS HIGH
CARBOHYDRATE,
HIGH SALT,
DRUGS-BETA
AGONISTS, INSULIN
REST FOLLOWING
PROLONGED
EXERCISE
REST AFTER
EXERCISE
STRESS
FATIGUE
FOOD HIGH IN
POTASSIUM
ALCOHOL
INFECTION
POSTASSIUM
SUPPLEMENTATION
TREATMENT PROVOCATIVE TEST
14. SERUM
POTASSIUM
CONCENTRATION
LOW HIGH, NORMAL
ECG HYPOKALEMIC
CHANGES
HYPERKALEMIC CHANGES
CHANGES
MUSCLE BIOPSY SINGLE OR MULTIPLE
CENTRALLY PLACED
VACUOLES
SMALLER, LESS
NUMEROUS
PERIPHERALLY PLACED
VACUOLES
NERVE CONDUCTION TEST REDUCED
AMPLITUDE OF
ACTION POTENTIAL
REDUCED AMPLITUDE OF
ACTION POTENTIAL
ELECTROMYGRAPHY ELECTRICALLY SILENT ELECTRICALLY SILENT
MYOTONIC DISCHARGE
BETWEEN ATTACKS
GENETIC STUDY CALCL1A3, SCN4A SCN4A
18. OUTLINE
• DIFFERENTIAL
DIAGNOSIS OF AIDP
• PRESENTATON OF AIDP
• CAUSES OF PERIODIC
PARALYSIS
• PRESENTATION OF
HYPOKALEMIC PP
• COMPARISON
BETWEEN AIDP Vs
Hypo PP
21. AIDP
• The most common acute neuromuscular disease seen in the intensive care
unit is GBS
Epidemiology
• incidence 2 /100,000/year.
• Sex
• M/F 1.1-1.7:1
• Age
• 2 months to 95 years
• Average 15-35 years
• Childhood GBS average age is 4-8 years
22. Antecedent events (causes)
• 60-70% cases –post infectious .
– 1-3 weeks after an acute infectious process respiratory or
GIT.
– 20-30% cases –campylobacter jejuni
– Other agents –HHV (EBV,CMV)
– Mycoplasma pneumoniae
• Recent immunisation –swine influenza vaccine,older
rabies vaccine (nervous system)
• Can be seen in patients with lymphoma,HIV
positive,SLE.
23. Presentation
• FEVER AND CONSTITUTIONAL SYMPTOMS ARE ABSENT AT THE ONSET
AND IF PRESENT ,CAST DOUBT ON DIAGNOSIS.
• Progressive weakness usually begins in the feet. at
presentation, 60% have weakness in all 4 limbs. usually
symmetric.
• GBS with a descending pattern of weakness seen in 14%
cases.
• Paresthesias often precede the onset of weakness by 1 or
more days. Often gait ataxia with distal limb
paresthesias. Pain, temp relatively spared.
• At presentation half have some facial weakness
• Ophthalmoparesis see in 10-20% of patients. (around
10%.Dyck and Thomas ). Abducens palsy most common;
usually bilateral.
24. Oropharyngeal weakness present in almost 50% of
cases
>1/3 require mechanical ventilation
Areflexia: 70% at presentation and eventually in all
58 to 76% of patients have sensory NCS abnormalities
(Oh et al, NEUROLOGY 2001)
Autonomic dysfunction two thirds of patients. most
common is sinus tachycardia. Retention of urine 1/3
cases, GI dysmotility 15% (Semin Neurol 2008)
plateaus 50% in 2 weeks, over 90% by 4 weeks
Improvement usually begins 1-4 weeks after the plateau.
25. IMMUNOPATHOGENESIS
• An autoimmune basis.
• Both cellular and humoral immunity involved.
• T cells activation –IL2,IL2 receptor,IL-6,TNF alpha,IFN gamma.
• All GBS results from immune responses to non self
anitgnes(infectious agents,vaccines) that misdirect to host
nerve tissue through a resemblance of epitope(molecular
mimicry).
• Neural targets are gangliosides.
• Anti ganglioside ab –GM1 (20-50% cases of C.jejuni)
• Anti GQ1b ab - >90% MFS
26.
27. GM1 on nerve, nodes of ranvier
Anti GB1 ab as part of
molecular mimicry
Complement mediated injury at
Paranodal axon – glial junction
Disrupts the cluster of sodium
channels
Conduction block
Flaccid paralysis
28. Asbury Criteria for diagnosis
REQUIRED :
• 1.progressive weakness of 2 or more limbs due to neuropathy.
• 2.areflexia
• 3.disease course < 4 weeks
• 4 exclusion of other causes (vasculitis,PAN,SLE,churg strauss
syndrome,toxins,lead,botulism,diptheria,porphyria.,cauda equinal
syndrome)
SUPPORTIVE:
• 1.relatively symmetric weakness
• 2.mild sensory involvement
• 3.facial nerve or other cranial nerve involvement
• 4.absence of fever
• 5.typical CSF profile(aceelualr,increase in protein level)
• 6.electrophysiologic evidence of demyelination
29. Variants
• MFS: most common variant, ophthalmoplegia, areflexia, and ataxia usually in
adults, also common in children. Most have GQ1b Ab
• Regional variants : eg pharyngeal-cervical-brachial weakness are rare (acute
progression of oropharyngeal, neck, and shoulder weakness. facial palsy,
blepharoptosis, no sensory disturbance, preserved DTR in the legs, elevated CSF
protein and denervation and decreased conduction velocity on EMG, reported in
1986 by Ropper )
• Pure pandysautonomia usually no weakness, many have areflexia
• AMAN China, developing countries. weakness only. little or no demyelination or
inflammation, more prevalent in kids
• AMSAN
30. Work up
• ESR and SE are normal ,Sometimes Liver enzymes
are elevated
Albuminocytologic dissociation on CSF
• protein > 55mg/dl
• cells <10 mononuclear leukocytes/ml
• 2/3 in 1st week, 82% have it by 2 weeks after
symptom onset.
• no association with clinical severity.
• Some have oligoclonal bands or Myelin basic protein
31. • Early on, NCS often normal.
• 90% are abnormal within 3 weeks of onset.
• 3 of the 4 NCS criteria = clear primary demyelinating neuropathy
(Cornblath)
• Reduced conduction velocity
• Conduction block or abnormal dispersion
• Prolonged distal latencies
• Prolonged F-waves
• Autonomic tests
• PFT: FVC < 20 mL/kg ICU; FVC< 15mL/kg or NIF<-25 Intubation
• Nerve biopsy if prolonged clinical course.
32. Treatment
• Initiate as soon as possible.
• Each day counts 2 weeks after the first motor symptoms –
immunotherapy is no longer effective.
• IVIg IVIg-first choice,easy to administer Five daily infusions
2g/kg body weight
• Plasmapheresis - 40-50ml/kg four times a week
• Combination is not effective
• Treatment reduces need for ventilation by half.,increases full
recovery at an year.
• Glucocorticoids are not effective in GBS.
• Conservative management in mild cases.
33. Prognosis
• total recovery in adults around 75%
• during the early stage of GBS, increasing severity in neurologic
disability scores ,cranial nerve involvement, urinary
incontinence, respiratory signs, and the need for ventilator
support are associated with poor prognoses
• Low CMAP amplitudes (< 20% of normal) bad prognostic
indicator.
• 10% may have a relapse in 1-6 weeks after completing
immunomodulatory therapy
• 15% end up with significant neurological residuals
• Mortality 2-6 %
36. HYPOKALEMIC PERIODIC PARALYSIS
MUTATED GENE CALCL1A3 SCN4A
CHROMOSOME 1q31 17q
DEFECTIVE
CHANNEL
CALCIUM SODIUM
MODE OF
INHERITENCE
AUTOSOMAL DOMINANT
TYPE 1 TYPE 2
37. HYPOKALEMIC PERIODIC PARALYSIS
PREVELANCE 1:100,000, AD
AGE OF ONSET FIRST AND SECOND DECADE OF
LIFE
M:F 3 or 4:1
SYMPTOMS DURING ATTACKS Occur anytime of the day; more
common in morning
Absence of myotonia
Proximal > distal weakness; legs
> arms
Sparing of facial, ventilatory
and sphincter muscles
Lasts several hours to more
than a day
38. HYPOKALEMIC PERIODIC PARALYSIS
SYMPTOMS BETWEEN ATTACKS REGAIN FULL STRENGTH
BETWEEN ATTACKS
TRIGGERS HIGH CARBOHYDRATE,HIGH
SALT,
DRUGS- BETA AGONISTS,
INSULIN
REST FOLLOWING PROLONGED
EXERCISE
FEVER /LACK OF SLEEP/STRESS
ETOH consumption
39. SERUM POTASSIUM
CONCENTRATION
LOW
ECG U waves, flattening of T
waves
MUSCLE BIOPSY SINGLE OR MULTIPLE
CENTRALLY PLACED
VACUOLES
NERVE CONDUCTION TEST REDUCED AMPLITUDE OF
ACTION POTENTIAL
ELECTROMYGRAPHY ELECTRICALLY SILENT
40. TREATMENT ORAL KCL
SUPPLEMENTATION
KCL VIA INFUSION
DONOT GIVE IN DEXTROSE
PROPHYLAXIS ACETAZOLAMIDE
(125-1000 Mg)
PROGNOSIS USUALLY GOOD
RARE DEVELOPMENT OF
PROXIMAL MYOPATHY
*Never forget to measure the thyroid hormones.
42. • Frequency Of Attacks : highly variable
• Frequency decreases after age 30; may become
attack free in 40s and 50s
• Permanent fixed weakness or slowly progressive
weakness more common with HypoKPP1
42
PROGNOSIS
43. SUMMARY
• 1.acute rapidly evolving areflexic ascending motor paralysis
with or without sensory disturbances.
• 2.fever is absent at the onset of weakness
• 3.bladder involvement in severe cases –transient
• 4.campylobacter jejuni 20-30 % cases
• 5.autoimmune basis ,molecular mimicry
• 6.anti GM1 ab (MC),anti GD1a,anti GQ1b (MFS)
• 7.autonomic involvement is common
• 8.facial nerve is the one most commonly affected,optic nerve.
• 9.30% require ventilatory support.
44. • 10.course is usually < 4 weeks
• 11 .typical CSF profile shows high protein,no pleocytosis
• 12.electrographically conduction block present
• 13.treatment as soon as possible
• 14.IVIg,plasmapheresis –both are equally good
• 15.glucocorticoids are not effective in GBS
• 16.think of miller fischer variant in presence of
ophthalmoplegia,ataxia,areflexia.
45. HYPOKALEMIC AIDP
PREVELANCE 1:100,000 AD M>>>F 2:100,000 S M>F
AGE OF ONSET FIRST AND SECOND
DECADE OF LIFE
ANY AGE SROUP[MC 2-
4]
SYMPTOMS ACUTE ONSELT FLACCID
PARALYSIS
PROXIMAL >>> DISTAL
WITHOUT SENSORY
COMPLAINTS BUT BODY
ACHE PRESENT
ASCENDING WEAKNESS
OF PROXIMAL AND
DISTALMUSCLES WITH
PARASTHESIAS AND
PAIN
CRANIAL
NERVE/BULBAR/RESPIR
ATORY MUSCLE
INVOVLMENT
RARELY SEEN
BLADDER/BOWEL- NOT
SEEN
AUTONOMIC
DYSFUNTION - ABSENT
COMMON++++
URINARY RETENTION +
CONSTIPATION +
COMMONLY+++
TRIGGERS HIGH CARBOHYDRATE,
HIGH SALT,FEVER
DRUGS-BETA
AGONISTS, INSULIN
REST FOLLOWING
H/O OF FEBRILE ILLNESS
WITH GIT/RS
INVOVLMENT PRIOR TO
WEAKNESS IN 66%.H/O
VACINATIONS+
46. HYPOKALEMIC AIDP
COURSE Episodic
Lasts several hours to
more than a day
AttacksFrequency :
highly variable
Frequency decreases
after age 30; may
become attack free in
40s and 50s
Permanent fixed
weakness or slowly
progressive weakness
more common with
HypoKPP1
Progressive initially
plateaus 50% in 2
weeks, over 90% by 4
weeks Improvement
usually begins 1-4
weeks after the plateau
3 attacks or >8 weeks -
CIDP
47. SERUM
POTASSIUM
CONCENTRATION
LOW NORMAL
ECG U waves, flattening of
T waves
TACHYCARDIA 2nd or 3rd
degree conduction
block, QRS
prolongation and T
wave abnormality
MUSCLE BIOPSY SINGLE OR MULTIPLE
CENTRALLY PLACED
VACUOLES
NI/NORMAL
NERVE CONDUCTION
TEST/EMG
REDUCED
AMPLITUDE OF
ACTION
POTENTIAL/EMG
ELECTRICALLY SILENT
Primary
demyelinating
neuropathy
CSF EXAM NI/NORMAL Albuminocytologic
dissociation on CSF
