Neurology Case Presentation Dr. M. A. Sofi MD; FRCP (London): FRCPEdin; FRCSEdin

19 year old male admitted with acute onset generalized weakness for 1 day duration Woke up with diffuse weakness; no anti gravity strength in arms, unable to get out of bed Proximal > distal weakness; bilaterally symmetrical Denied diplopia, dysphagia, dysarthria, facial droop, drooling or change in level of consciousness 2 Case history

PMH: similar episode in Feb 2013, admitted to local hospital for 4-5 days, ?? Diagnosed with GBS, ?? treated with plasmapheresis, no LP/ EMG PMH: nil significant Home meds: None FH: Nil for HTN, migraine, DM, asthma, no similar problem in family members SH: denies smoking, ETOH or illicit drug use 3 Case history

Vitals stable General physical exam unremarkable Neurological exam – Mental status: AAO * 3 – Speech : fluent with comprehension intact – CN 2-12: PERRLA, EOMI, normal facial sensation and symmetry, normal facial strength, hearing intact, equal palatal elevation and tongue midline 4 Physical exam

– Motor: Flaccid tone, motor strength 2/5 proximally and 3-4/5 distally BUE and BLE – DTRs: Areflexic, planter both down going – Sensory: Intact to LT/PP/ Vibration and proprioception – Unable to test for cerebellar function and gait 5 Case history

Where?? What?? 6 Case scenario

Hb , WBC 6.1, Plt count 215 Sodium 143, K 1.3, Chloride 110, BUN 13, Creatinine 0.83, Glucose 151, Calcium 9.3, Magnesium 2.0, Phosphorus 2.4 CK 493, Aldolase 15.7 (on day 3) TSH: 2.082, free T3 – 3.8, free T4 – 0.9 Urine electrolytes: unremarkable 7 Labs

Aggressive Potassium replacement Started showing improvement in muscle strength on day 1 By day 2 – strength was 5/5 BUE and BLE Diagnosed with familial hypokalemic periodic paralysis Discharged with follow up care 8 Hospital course

The skeletal muscle genetic ion channelopathies are a distinct group of diseases caused by mutations which mainly occur in voltage-gated ion channel genes. They can be classified in to 2 categories – non dystrophic myotonias and periodic paralyses. NDMs are a group of conditions characterized by muscle stiffness on voluntary movement due to delayed skeletal muscle relaxation. This group includes : Myotonia congenita Paramyotonia congenita Sodium channel myotonias (potassium-aggravated myotonias (PAMs) Myotonia fluctuans Myotonia permanens Acetazolamide responsive myotonia The NDMs are mainly distinguished clinically from the dystrophic myotonias, myotonic dystrophy types 1 and 2, by the absence of extramuscular systemic involvement. Muscle channelopathies

The periodic paralyses are a group of autosomal- dominant disorders characterized by episodes of flaccid paralysis often triggered by an alteration in serum potassium concentration. They include hypokalemic periodic paralyses type 1 and 2, hyperkalemic periodic paralysis and Anderson Tawil syndrome Muscle channelopathies

Non dystrophic myotonias – Myotonia congenita (CLCN1) – Paramyotonia congenita (SCN4A) – Sodium channel myotonias (potassium aggravated myotonias) (SCN4A) Periodic paralyses – Hypokalemic (CACNA1S/ SCN4A) – Hyperkalemic (SCN4A) – Anderson Tawil syndrome (KCNJ2) 11 Muscle channelopathies

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 12 Periodic Paralysis Secondary

HypoKPP1 and 2 - CACNA1S/ SCN4A gene HypoKPP 1 is the most frequent form 1 in 100,000 Autosomal dominant inheritance pattern M:F – 3 or 4:1 Onset: first 2 decades of life 13 Hypokalemic periodic paralysis

Flaccid paralysis – mild focal weakness to severe generalized weakness 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 14 Clinical features

15 Effects of hypokalaemia on the ECG Changes appear when K+ falls below about 2.7 mmol/l Increased amplitude and width of the P wave Prolongation of the PR interval T wave flattening and inversion ST depression Prominent U waves(best seen in the precordial leads) Apparent long QT interval due to fusion of the T and U waves (= long QU interval)

Frequency: 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 Attacks may be preceded by sensation of heaviness and or aching in the low back 16 Hypokalemic periodic paralysis

Strenuous physical activity followed by rest or sleep High carb diet ETOH consumption Emotional stress Concurrent viral illness Lack of sleep Medications like beta agonists, corticosteroids, and insulin 17 Precipitating factors

Serum K < 3.0mEq/L Serum CK level elevated EKG changes – U waves, flattening of T waves Provocative testing - Intravenous glucose load/ insulin Electrophysiology – Sensory and motor NCS normal between attacks – During attacks – small CMAP. Reduced insertional activity, fibs and positive sharp waves – No myotonia on EMG – Short/ long exercise test 18 Diagnostic studies

Reducing exposure to known triggers Acute treatment – replacement of K Acetazolamide – prevent attack recurrence and severity – Acetazolamide may ppt weakness in HypoK PP2 Dichlorphenamide – no longer available Triamterene and spironolactone 19 Treatment

A 38-year-old man, feeling poorly after finishing a marathon, was brought to the medical tent near the finish line. He had run three marathons in the past two years. He was confused, but not hypotensive; pulse was 130 beats/min; his weight was 4.5 kgm higher than at the start of the race. Electrolyte measurements on site included a serum sodium concentration of 118 mEq/L. The most likely proximate reason for the hyponatremia is: A.Cerebral salt wasting B.NaCl-wasting nephropathy C.Excessive intake of hypotonic fluid D.Excessive sweating

A 60-year-old man with known lung cancer is seen in follow-up with no major symptomatic changes. His BP is 150/90 mmHg, pulse 86 and regular and he has no edema. Electrolytes reveal a serum sodium concentration of 125 mEq/L; BUN is 6mg/dl, uric acid is 2.8 mg/dl, and the urine osmolality is 280 mosm/kg. The most likely explanation for the hyponatremia is: A.Cerebral salt wasting B.Diuretic use/abuse C.SIADH D.Psychogenic polydipsia

The most appropriate therapy for patient #2 is: A.Solute-free water restriction B.DDAVP C.Cortisone D.5% hypertonic saline

60 Year old presented with recurrent attacks of syncope 1.What does ECG rhythm strip show? _______ 2.What treatment is recommended? ________

67 year old man presented with left side hemiplegia 1.Describe CT finding? ___ 2.What vascular territory is involved? _____

1.What is the diagnosis? _________ 2.What blood test has diagnostic value? _______________ Presented with severe acute pain inability to move foot.

On arrival, he is sweaty, distressed and peripherally cyanosed Vital Signs: RR45/min intercostal recession Tempt38 deg C BP 180/90 mmHg Upon arrival, arterial blood gases are taken (on 12L / min of O2): pH 7.15 (7.35 – 7.45) PO2 80 mmHg (80 – 95) PCO295 mmHg (35 -45) HCO342mmol/L (22 – 28) Base Excess + 17 ( ) SaO290% A 65 year-old man with severe dyspnoea. The patient has a history of Chronic Obstructive Airway Disease (COAD), with regular use of bronchodilators. He is still a heavy smoker, but has no other relevant past history. Name 2 abnormalities of blood gas analysis above? 1.___________ 2.___________