hpp.pptx hyperkalemic periodic paralysis

Hppppppp

1. HYPERKALEMIC PP VS HYPOKALEMIC PERODIC PARALYSIS

2. OUTLINE Causes Of Primary Periodic paralysis Causes Of Secondary Periodic paralysis PRESENTATION OF HYPERKALEMIC PP COMPARISON BETWEEN Hyper PP Vs Hypo PP

3. Primary Periodic paralysis Secondary Periodic paralysis Causes of Primary Periodic paralysis Hypokalemic (CACNA1S/ SCN4A) Hyperkalemic (SCN4A) Anderson Tawil syndrome (KCNJ2) 3 Periodic paralysis

4. Secondary Periodic Paralysis Hypokalemic: Thyrotoxic periodic paralysis hyperaldosteronism RTA villous adenoma cocaine binge diuretics, licorice, steroids, ETOH Hyperkalemic (k>5.5 ) hyporeninemic hypoaldosteronism (DM/CKD)  ( ie , GFR or ≤ 20 mL/min). type IV renal tubular acidosis (RTA) AKI/Metabolic acidosis High oral K, DRUGS chronic heparin therapy Rhabdomyolysis Adrenal insufficiency 4

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6. HYPERKALEMIC PERIODIC PARALYSIS MUTATED GENE SCN4A CHROMOSOME 17q DEFECTIVE CHANNEL SODIUM MODE OF INHERITENCE AUTOSOMAL DOMINANT

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 SMALL ER, 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

15. TREATMENT MILD SUSTAINED EXERCISE LOW POTASSIUM DIET BETA AGONIST THIAZIDES HIGH SUGAR LOAD CALCIUM GLUCONATE PROPHYLAXIS ACETAZOLAMIDE , MEXILETINE (125-1000 Mg)

16. ACUTE ONSET WEAKNESS –AIDP VS HYPOKALEMIC PERODIC PARALYSIS

17. OUTLINE DIFFERENTIAL DIAGNOSIS OF AIDP PRESENTATON OF AIDP CAUSES OF PERIODIC PARALYSIS PRESENTATION OF HYPOKALEMIC PP COMPARISON BETWEEN AIDP Vs Hypo PP

18. DIFFERENTIAL DIAGNOSIS OF AIDP PERIPHERAL NEUROPATHIES    Toxic    •     Vincristine    •     Glue sniffing    •     Heavy metal    •     Organophosphate pesticides    Infections    •     HIV    •     Diphtheria    •     Lyme disease    Inborn errors of metabolism    •     Leigh disease ( Subacute Necrotizing Encephalomyelopathy )    •     Tangier disease (Familial alpha-lipoprotein deficiency)    •     Porphyria    Critical illness: polyneuropathy SPINAL CORD LESIONS Acute transverse myelitis Epidural abscess  Tumors  Poliomyelitis  Vascular malformations  Cord infarction  Cord compression from vertebral subluxation related to congenital abnormalities or trauma  Acute disseminated encephalomyelitis (ADEM) NEUROMUSCULAR JUNCTION DISORDERS    Tick paralysis, myasthenia gravis, botulism, hypercalcemia Myopathies Periodic paralyses, dermatomyositis , critical illness myopathy

19. OTHER NAMES LANDRY’S ASCENDING PARALYSIS ACUTE INFLAMMATORY DEMYELINATING POLYNEUROPATHY (AIDP) ACUTE IDIOPATHIC POLYRADICULONEURITIS ACUTE IDIOPATHIC POLYNEURITIS FRENCH POLIO LANDRY GUILLAIN BARRE SYNDROME

20. 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

21. 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 .

22. 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.

23. 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.

24. 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

25. 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

26. 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

27. 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 1 st week, 82% have it by 2 weeks after symptom onset. no association with clinical severity. Some have oligoclonal bands or Myelin basic protein

28. 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.

29. 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.

30. 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 %

31. Primary Periodic paralysis Secondary Periodic paralysis Causes of Primary Periodic paralysis Hypokalemic (CACNA1S/ SCN4A) Hyperkalemic (SCN4A) Anderson Tawil syndrome (KCNJ2) 34 Periodic paralysis

32. Hypokalemic: Thyrotoxic periodic paralysis hyperaldosteronism RTA villous adenoma cocaine binge diuretics, licorice, steroids, ETOH Hyperkalemic (k>7): hyporenemic hypoaldosteronism (DM/CRF) oral K, CRF, chronic heparin, rhabdomyolysis Normakalemic : Guanidine, sleep paralysis, MG, TIA, conversion 35 SecondaryPeriodic Paralysis

33. HYPOKALEMIC PERIODIC PARALYSIS MUTATED GENE CALCL1A3 SCN4A CHROMOSOME 1q31 17q DEFECTIVE CHANNEL CALCIUM SODIUM MODE OF INHERITENCE AUTOSOMAL DOMINANT TYPE 1 TYPE 2

34. 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

35. 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

36. 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

37. 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.

38. Hypokalemic Periodic Paralysis 41

39. 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

40. 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.

41. 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 .

42. 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/RESPIRATORY 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 PROLONGED EXERCISE H/O OF FEBRILE ILLNESS WITH GIT/RS INVOVLMENT PRIOR TO WEAKNESS IN 66%.H/O VACINATIONS+

43. 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

44. 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