A CASE OF SEIZURE in a Young Girl

PROF.DR.MAGESHKUMAR’S UNITDevendra Patil

HISTORYI7 year old female pt presented with

• seizures 3 episodes since last 6 months.• GTCS; lasted for 5 mins,• Associated with frothing from mouth.• No h/o tongue bite, bladder and bowel disturbances.• With post ictal LOC • No h/o fever, head injury, altered sensorium.• No h/o vomiting, head ache, Blurring of vision.• No h/o chest pain, palpitation, dyspnea, syncope

PAST HISTORY:• Not a known case of DM/SHT/ CHD/BA/ TB• No h/o seizure in child hood or perinatal insult.• Pt studying in college. Performance is good.• Pt not on any chronic medications.• No h/o surgery in the past.Personal history: nil significant.Menstrual history: cycles regular, no

menorroghoea, dysmenorrhoea,

• ON EXAMINATION:• Pt conscious, oriented, afebrile.• Pulse : 78/ MIN, regular• Bp : 110/70 mm hg .• RR- 16/ min regular. Not in distress• No pallor, icterus, cyanosis, pedal edema,

cyanosis, clubbing, lymphadenopathy.

• CVS :S1, S2 heard. No murmurs.• RS: NVBS HEARD. No added sounds.• P/A : soft , non tender, no organomegaly, no

free fluid.

• CNS: • Higher functions: normal• Cranial nerves: normal • Spinomotor system:• Tone – normal• No motor deficit.• tendon reflexes – normal• Plantar- b/l flexor.• No cerbellar signs.• Fundus- normal

Provisional diagnosis seizures for evaluation

Lab investigations

CBC:Tc- 5100/cummDc – p -65. l-35Hb – 11.8 gmsPcv- 35%Platelets- 2 lakhs.

RFT:Urea- 34 mg, creat- 0.9 mgNa- 137 meq/l, k- 4, cl- 100, bicarb- 20meq/l

Urine routine:Albumin, sugar- nil.Pus cells -1to 3 cells /hpf

• Ecg :• Rate- 90/min• Regular ; normal axis ; p wave - normal• Pr interval- 120 msec• Qrs-0.08 sec• Qt interval- 448 msec• Bazets formula : Qtc- 546 msec • Rule of thumb in QT interval

CAUSES OF PROLONGED QTC• Hypokalemia• Hypocalcemia CARDIAC - • Acute myocarditis, acute MI, HOCM,• torsade de pointes.CONGENITAL- • Jervell-lange-nielsen syndrome• Romano-ward synd• Cerebral injury.• Hypothermia

• DRUGS:QUINIDINE,Procainamide, Tricyclic antidepressants.Antimalarials- halofantrine

• Chest radiograph : – NAD• Ct brain:- Normal study• EEG : Normal Study

Problems :• seizures• Prolonged QT in ECG• CT – Brain normal

• Serum calcium: 5.7 mg/dl[normal-8-10]

Investigations needed to work up a case of HYPOCALCEMIA

• Sr. Calcium ( total / ionised / unionised )• Sr. Albumin levels• Sr. Phosphate levels• Sr. Parathormone levels• ABG• 24 Hrs urinary calcium• Sr. Magnesium• Sr. 25 (OH)vit D levels• Sr. Alkaline Phosphatase levels

• Serum calcium: 5.7 mg/dl[normal-8-10]• Serum albumin : 3.8 gm /dl• Ionised calcium- 0.452 mmol/l[ 1.16-1.32]• Unionised calcium- 0.458 mmol/l• Serum Phosphorus : 6.2 (2.5 – 4.5 mmol/dl )• Serum PTH : 5.2pg/ml ( 8-51 pg/ml )• 24 Hrs urine Calcium : 7mg/L (< 300mg/day)• Sr. Alkaline Phosphatase : 37 IU/l ( 33-100)

ABG ( room air , at rest )Po2- 102.4mm hgPco2 -39.4 mm hgPh- 7.427Na -138.6. K- 3.17, Cl - 92.9 ( all in meq/l)Hco3 – 25.4 mmol/lOsmololity: 287.6 mosm/kgImpression : normal study.

Functional classification of hypocalcemia

PTH low/ absent: PTH ineffective Pth overwhelmed:

Hereditary

Acquired

Hypomagnesemia

CRF

Active VIT-D lacking:Reduced intake Low sunlightAnticonvulsant use Dependant rickets- type1

Active vitamin-d ineffective: Dependant rickets- type 2 Pseudo hypo PTH

severe acute hyperphosphatemia Tumour lysis ARF Rhabdomyolysis Burns Pancreatitis

Osteitis fibrosa after para thyroidectomy

• Serum magnesium: 2.1 mg/dl[1.7 to 2.55]• History didn’t suggest any cause that could lead

to acquired hypoparathyroidism• No significant history in family members• No facial dysmorphism ; short stature.• Skin –No hyperpigmentation / vitiligo / muco-

cutaneus candidiasis / abscess n scars / eczematous changes.

• Thyroid profile :Normal

• Further plan was:Anti parathyroid antibodiesDouble antigen PTH immune assayScreening for subclinical endocrine pathologies

Why this case was different

• Age of onset • Hypocalcemia without any evidence of signs

of peripheral neuro-muscular excitibility.• CT brain : not showing the evidence of basal

ganglia calcifications• Difference of treatment in a case of hypo PTH

as compared to HypoCa+ without hypoPTH

Age of onset

• Idiopathic and hereditary hypoparathyroidism usually manifest in the first decade but can present later.

Harrison 17/e

Clinical Manifestationof hypocalemia

• Neuromuscular– Numbness and tingling sensations in the perioral area or in the fingers and toes– Muscle cramps, particularly in the back and lower extremities; may progress to carpopedal spasm (ie, tetany)– Wheezing; may develop from bronchospasm– Dysphagia – Voice changes (due to laryngospasm)– Chovstek n Trosseau Sign ( Latent Tetany )

• Neurologic– Irritability, impaired intellectual capacity, depression, and personality changes– Fatigue– Seizures (eg, grand mal, petit mal, focal) – Other uncontrolled movements

• Cardiac– Shortness of breath– Symptoms of congestive heart failure (possible)

• Skin– Coarse hair– Brittle nails– Psoriasis– Dry skin

• Eyes-- subcapsular cataract

Few articles

• Arq. Neuro-Psiquiatr. vol.62 no.1 São Paulo Mar. 2004• doi: 10.1590/S0004-282X2004000100028 • Hypocalcemic myopathy without tetany due to idiopathic hypoparathyroidism: case report• Myopathy due to idiopathic hypoparathyroidism is very unusual. We report on a 30 years-old man

referred with complaints of sporadic muscle pain and mild global weakness for 10 years. His physical examination showed normal strength in distal muscle and slightly weakness in the pelvic

and scapular girdles with no atrophy. Deep muscle reflexes were slightly hypoactive. Trousseau's and Chvostek's signs were absent. He had bilateral cataract and complex partial seizures. His laboratory tests showed decreased ionised and total calcium and parathyroid hormone and increased muscle enzymes. EMG and muscle biopsy was compatible with metabolic myopathy. After treatment with calcium and vitamin D supplementation he showed clinical, neurophisiological and laboratorial improvement. In conclusion: patients with muscle symptoms, even when non-specific and with normal neurological examination, should have serum calcium checked, as myopathy due to idiopathic hypoparathyroidism, even being rare, is treatable and easy to diagnose.

• J Med Case Reports. 2007 Dec 3;1:167.• Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old

man: a case report.• Tonelli AR, Kosuri K, Wei S, Chick D.• A 40-year-old man without significant past medical history presented with a new-onset generalized

tonic-clonic seizure. He had no personal history of hypocalcemia or seizures. Physical examination

was remarkable for short stature, hypertelorism, prominent forehead and nasal voice. Trousseau's and Chvostek's signs were absent. His initial laboratory examination showed hypocalcemia (Calcium 5.2 mg/dl and Calcium ionized 0.69 mmol/l) with hypoparathyroidism (Parathyroid hormone intact < 2.5 pg/ml. NV: 14-72 pg/ml). Urine Calcium was 3 mg/dl on a spot and 88 mg in a 24-hour urine collection (NV: 100-300 mg/24 hs). The electrocardiogram showed a prolonged corrected QT interval. Echocardiogram, abdominal ultrasound and electroencephalogram were normal. A computer tomography of the brain showed basal ganglia calcification. The subtle physical findings and the presence of idiopathic hypoparathyroidism motivated the performance of fluorescent in situ hybridization which demonstrated a microdeletion on one of the homologs 22q11.2. The patient was treated with calcium citrate and calcitriol with good response.

• [Idiopathic hypoparathyroidism, a syndrome with various clinical expressions: analysis of 10 cases]

Rev Med Chil. 1989 Jun;117(6):647-52.

• Abstract• We report 10 patients with primary hypoparathyroidism. Age at onset varied from 7 months to 52

years (mean 28); 7 were female. Diagnosis was established at a mean of 4.1 years after the appearance of clinical manifestations. Unexplained hypocalcemia (mean 5.3 mg/dl) and hyperphosphatemia (mean 6.4 mg/dl) were present in all patients. Prevalent symptoms included tetany (9 patients), seizures (5) and hypocalcemic cataracts (4). Clinical manifestations may be grouped into 5 types 1) tetany; 2) seizures; 3) other neurologic disorders (basal ganglia calcification, pseudotumor of the brain, ataxia, nystagmus, hypertonus, paresis); 4) disorders of the lens including fully developed cataracts and 5) skin alterations like psoriasis and others. Some of these run on acute course (seizures, tetany), others a subacute one (skin alterations) while others are rather chronic (cataract and other neurologic disorders). Seizures and electroencephalographic disorders predominate in younger patients while tetany is more prevalent in older subjects.

• The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 4 1476-1477 , 2003• IMAGES IN CLINICAL ENDOCRINOLOGY• Calcification of the Basal Ganglia in Chronic Hypoparathyroidism • An 80-yr-old man with a more than 60-yr history of postsurgical hypoparathyroidism was evaluated

for hypocalcemia detected during hospitalization after a fall. The patient had long-standing

intermittent paresthesias in his distal extremities, but denied muscle cramps, tetany, or seizures. His past medical history was remarkable for an episode of nephrolithiasis in his 20s. He had been

taking up to 4000 mg calcium carbonate (oral, daily) before admission. On examination, Chvostek and Trousseau signs, tremor, and rigidity were absent. Laboratory studies included: 5.9 mg/dl serum calcium (normal range, 8.4–10.5), 0.78 mmol/liter ionized calcium (normal range, 1.13–1.32), 6.7 mg/dl phosphate (normal range, 2.7–4.5), 3.2 g/dl albumin (normal range, 3.5–5.3), and 1 pg/ml intact PTH (normal range, 10–65). In Fig. 1, brain computed tomography showed diffuse, symmetric parenchymal calcifications involving the dentate nuclei (A), thalami (B, curved arrow), globus palladi (B, arrowhead), caudate heads (B, straight arrow), and deep cerebral white matter (C). The patient was treated with 0.5 µg calcitriol and 1000 mg calcium carbonate (oral, daily). After 1 week, his chronic paresthesias resolved and serum calcium rose to 9.2 mg/dl.

Absence of Basal Ganglia calcification

• Upto 30 % of cases of Hypocalcemia have basal ganglia calcificationBASAL GANGLIA CALCIFICATIONBirth anoxia Idiopathic (most common) bilateral and symmetrical

Toxoplasmosis / CMV - usually not limited to basal ganglia

Hypoparathyroidism / pseudohypoparathyroidism

Fahr syndromeCockayne syndrome

• Garg R, Garg N, Tandon N, Khurana ML, Ammini AC. Idiopathic hypoparathyroidism presenting as epilepsy in a 40 years female. Neurol India 1999;47:244

• The patient was a 40 year old female who complained of generalized tonic clonic seizures for the last 4 years. The seizures used to occur once in every 2-3 months. positive Chvostek's and Trousseau's signs. Nervous system examination was normal. Investigations revealed a serum calcium level of 6.4 mg/dl (normal - 8.5-10.5 mg/dl) and serum phosphate level of 6.4 mg/dl (normal - 2.5-4.5 mg/dl). Serum albumin was 4.0 G/dl (normal - 3.8-4.0 G/dl) and renal function tests were normal. Serum alkaline phosphatase level was 8.8 KA units (normal - 3-13 KA units). Serum parathyroid hormone levels were 28 pg/ml (normal - 11-55 pg/ml) which were inappropriately low in the presence of hypocalcaemia. Plasma cortisol, thyroxin and gonadotropins were within normal range. EEG showed generalized spike and wave pattern. CT scan of the head was normal.

• Idiopathic hypoparathyroidism presenting as dementia.

D ErautBr Med J. 1974 March 9; 1(5905): 429–430. PMCID: PMC1633226Summary: 80 yr old male ……

Difference of treatment

1. High dose of vitamin D ( 20000 IU /day )( 100-120 times the RDA of Vit D )Why ?2. High dose of oral Calcium 3. Monitoring of urinary Ca to avoid the

risk of nephrolithiasisProphylactic use of Thiazide

Final Diagnosis :Hypocalcemia induced seizuresHypoparathyroidismMostly Idiopathic variety

THANK - YOU

Hereditary hypoparathyroidism May occur without any other endocrinological and

dermatological manifestations. Manifest within first decade or later.• Syndrome associated with hypopara thyroidism• Di George syndrome[ DSG1-chromosome-22. DSG1-

Chromosome10].• Kenney- Caffey syndrome: hypo parathyroidism, short

stature, osteo sclerosis, thick cortical bones.• Sanjad-Sakati synd: growth failure and dysmorphic

features. Basal ganglia calcification and extra pyramidal symptoms

are more common and earlier in onset.

Poly glandular auto immune type-1 deficiency:Mutation in APECED GENE.childhood onset. Disease association: muco cuateneous candidiasis,

hypo parathyroidism, adrenal insufficiency, hypogonadism, alopecia, hypothyroidism, dental enamel hypoplasia, mal absorption, vitiligo, chronic active hepatitis, pernicious anemia.

Kearns - Sayre and MELAS syndrome

AD- hypocalacemic hypercalciuria:• Abnormality in calcium sensing receptor.• Receptor senses normal calcium level as

excessive and suppresses pth secretion.• Increased renal excretion of calcium.• External calcium and vit-D supplements

exacerbate the symptoms leading to irreversible renal damage due to renal stones or ectopic calcifications.

Acquired hypoparathyroidism

• Surgery- para thyroidectomy for hyper para thyroidism.

• Irradiation .• Hemochromatosis. hemosiderosis.

Calcium Regulation

• 99% of body calcium in skeleton• Miscible Pool: 40% bound to protein, 13%

complexed w/ anions, 47% free ionized• PTH: Increased Ca, Decreased PO4, Increased

Vitamin D• Vitamin D: Increased Ca, Increased PO4,

Decreased PTH (slow)• Kidney, Bones, GI Tract

• Acute Hypocalcemia: Parathyroidectomy

– PTH undetectable at 8 hours

– Normalizes by 30 hours

– Calcium nadir at 20 hours, normal Day 2-3

– Hungry bone syndrome – Old, Labs

• Medications: I-131, Cimetidine, ETOH, Cisplatin, Digoxin, Ampho-B

– Hypomagnesemia

Hypocalcemia/Hypoparathyroidism

Hypocalcemia/Hypoparathyroidism

• Neuro: Paresthesias, fasciculations, muscle spasm, tetany, irritability, movement disorder, SEIZURE, laryngeal spasm.

• Visual: Cataracts, optic neuritis, papilledema- in association with increased ict

• Pulmonary: Bronchospasm• CV: Prolonged QT, CHF, Hypotension, digitalis

effect may be reduced.• GI: Dysphagia, abdominal pain, biliary colic• GU: Preterm labor• Psychiatric- depression, psychosis.• Chvostek’s sign and trousseau’s sgn can be used

latent tetany.

Hypoparathyroidism: Treatment

• Acute severe hypocalcemia

– Check ionized Ca

– 100-300 mg (10-30 ml) 10% Ca-gluconate in 150 cc D5W over 10 minutes

– Continuous infusion at 0.5 mg/kg/hr

– EKG monitoring

– Check Magnesium

– Check Phosphorous

Hypoparathyroidism: Treatment

TREATMENT

• Vitamin-D - 40000 to 1,20,000 iu/day[ 1-3 mg /day] combined with elemental calcium is satisfactory.

• Calcitriol- 0.5 to 1 micro gram/day.• They do not reverse the lowered urinary

calcium reabsorption.• Thiazide diuretics lower urinary calcium in

hypoparathyroid pts on vit-D.

HYPOMAGNESEMIA• Levels less than 0.4 mmol/l[ 0.8 meq/l]• Reduced PTH secretion or reduced response to

PTH• Severe hypomagnesemia is paradoxically

associated with low PTH level. Cause unknown.• Serum phosphate levels are usually not elevated.• When magnesium is repleted restoration of PTH

levels may preceed serum calcium by several days.

• Treatment- IV magnesium.

PTH overwhelmed

• Loss of ca from ECF is so severe that PTH cannot compensate.

• Pancreatitis,• Acute hyper phosphatemia- due to cell

destruction, tissue damage.• Renal failure.• PTH raises in response to hypocalcemia but

serum calcium do not return to normal.

Differential diagnosis of hypoclcemia

Low calcium, high phosphate- hypoparathroidism, psudo hypoparathyroidism.

Low calcium, low phosphate-absent or ineffective vitamin D.

Hypo magnesemia.Nutritional deficiency in alcohol.