a case of oro-facio-bulbar weakness

DR.MAHESH KUMAR’S UNIT.

Case historySikkandar ,70 yrs male,retd from TNEB3 months ago,initially had fever /URI/ear block

which lasted for 5 days,subsided with RX.Later noticed insidious onset of diplopia&difficulty

in eye closurenasal speechdifficulty in chewing/swallowing&nasal regurgitation.

No h/o difficulty in smell perception. disturbances in color vision. altered sensory perception over face .

No h/o

HOH/tinnitus/vertigo

difficulty in turning from side to side/shoulder shrug

motor weakness of the arms & legs

sensory deficit/positive/negative sensory phenomena

involuntary movements

seizures/headache/vomiting/head injury

previous similar episodes

Not a known TB/DM/HT patient;no high risk behaviour.

o/e no neurocutaneous markers ht neck ratio normal vitals stable.Examination of CNS:HF:normal,MMSE:28/30

Cranial nerves Rt Lt

1.Smell perception Normal Normal

2.Visual acuity field of vision color vision fundus

Normal Normal

3,4,6 palpebral fissure pupil size&reacn EOM

ptosis +3 mm,reacn normalFull

Ptosis+3 mm ,reacn normalFull

5.Sensory perception muscles of mastication jaw jerk

Normal Weak Not exaggerated

Normal Weak Not exaggerated

7.Raising eyebrows eye closure pursing &whistling taste over ant 2/3

Weak Not completeNot possibleNormal

Weak Not completeNot possibleNormal

8. Rinne ‘ s test weber ‘s test

Positive Not lateralized

Positive Not lateralized

9&10Palatal reflex gag reflex

diminished diminished

11. Power of SCM shoulder shrug

Normal Normal

12. Size wasting strength fasciculations

Normal No Decreased No

Normal No Decreased No

Motor system: no muscle wasting/weakness supercial &deep tendon reflexes normalGait normalSensory system:normalNo cerebellar signsSpine &cranium normalOther systems:no abnormality detected.

orofaciobulbar weakness

DD?

DD of orofaciobulbar weakness1.Neurasthenia /depression2.Progressive external ophthalmoplegia3.Polymyositis /inclusion body myositis4.Congenital myasthenic states5.Progressive bulbar palsy6.Multiple sclerosis7.Stroke 8.GBS variants –Miller-fisher variant9.Initial stages of botulism

DD -contd..MCNP syndromes: Intracranial –extramedullary or extracranial

processes1.Neoplastic meningitis2.Nasopharyngeal carcinoma3.Osteopetrosis4.Vertebro-basilar dolichoectasia5.Neurosarcoidosis 6.Polyneuritis cranialis(GBS variant)7.Bannwarth ‘s syndrome(lyme disease)

Investigations done CBC:Hb :11 g% TC:8000 DC:P65L33E2 ESR:2/5RFT: Sugar:110 urea:22 creatinine:0.7ECG:NSR,WNLCXR:WNLMRI BRAIN:No significant abnormalityRNS:Done at 2 HZ,recording from the orbicularis

oculi,nasalis,deltoid.Normal amplitudes obtained with significant

decremental response in the nasalis,deltoid&orbicularis;consistent with MG.s

Sr AchR abs:18.98(neg <0.25;positive>0.40)CT thorax:No significant abnormalityTFT:normalRhematoid factor:negativeCRP:negativeANA:1:10 dilution &1:40 dilution

positive;speckledECHO:normal Lv systolic function;no RWMA

Treatment givenStarted on ,T.Pyridostigmine 60 mg qidT.Prednisolone 5 mg 2 od

MYASTHENIA GRAVIS

Myasthenia gravisA neuromuscular disorder,Characterised by, 1.weakness &fatiguability of skeletal

muscles 2.decrease in no of AchR at the NMJ due

to an antibody mediated autoimmune

attack.

PathophysiologyDecrease in the no of AchR at the post-synaptic

membrane;flattening of post-synaptic folds.Even with normal release of Ach end-plate

potentials are smallfailure to trigger MAP.Neuromuscular abnormalities d/t AchR abs.The abs are IgG and T cell dependent.The thymus plays a role in this process.?Myoid cells with AchR on surface-autoantigen

Clinical featuresAll age groups, women in 20-40 yrs&men in

50-60 yrs.Weakness increases with repeated use,may

improve following rest.Course variable with remissions and

exacerbations.Remissions rarely complete.

Muscle weakness-distributionCranial muscles: 1.lids &EOM are often the first affected. 2.facial weakness/ weakness in chewing. 3.nasal timbre to speech(palate)/dysarthric(tongue) 4.difficulty in swallowing/regurgitation. 5.bulbar weakness-esp with anti MUSK abLimb muscles 1.weakness generalizes in 80% 2.often proximal and asymmetric.

Others axial muscles. diaphragm/abdominal ms/intercostals. even the external sphincter of

bladder&bowel.Preserved DTR despite muscle weakness

Osserman’s grading Grade Weaknes

sProgress Crises Drug

responseIncidence

I Ocular ? No satisfactory

15-20%

II A Mild generalized

slow No satisfactory

30%

II B Moderately Severegeneralized

Slow No Less than satisfactory

25%

III Acute Fulminant

Rapid yes Poor 15%

IV Late severe

Steady Progression over 2 yrs

yes poor 10%

Diagnosis history/physical examinationLab 1.anti AchR radioimmunoassay 85% positive in generalized MG,50% in

ocular MG 40% of negative pts have antiMUSK abs. 2.repetitive nerve stimulation 3.single fiber EMG 4.tensilon test

Repetitive nerve stimulationAchEmedication stopped 6-24 hrs beforeBest to test weak/proximal musclesRepetitive stimulation of the nerve at 3/secDecremental response (decrease in muscle

CMAP)of atleast 10-15%Edrophonium can prevent this response.

Single fiber EMGMore sensitive than RNS.Identification of APs from single muscle

fibersInconstancy of the normally invariant interval

between firing of fibers connected to same motor unit(jitter)/blocking of successive discharges.

NCV &distal latencies are normal

Tensilon (AchE)testReserved for pts with neg abs/EDS.Edrophonium;onset:30 s,DOA:5 minAn objective endpoint selectedGiven in two divided doses(2+8 mg) to avoid

sideeffectAtropine should be kept ready.False +: ALS,placebo reactors

Disorders a/w MG1.Thymus Thymoma,hyperplasia2.Thyroid3.Autoimmune RA,SLE,sjogren’s and others4.Exacerbation of MG Hypo/hyperthyroidism,occult infn,stress etc5.Interference with therapy TB,DM,GIB,HT,BA,osteoporosis,obesity etc

lab testsCT/MRI of mediastinumANA/RF/anti thyroid absPPD skin testCXRFBS/HbA1cPFTBone densitometry in older pts.

Treatment Anticholinesterase drugsThymectomyImmunosuppressive agentsPlasmapheresis &IVIg

Pyridostigmine most widely used.Action begins in 15-30 min,lasts for 3-4 hrs.Rx started with 30-60 mg tds to qid.Tailored to individual requirements.Max useful dose rarely exceeds 120 mg every

3-6 hr.Over dosage may increased weakness.Muscarinic side effects in a few.Atropine/diphenoxylate can be used.

ThymectomyAdvantages :85% experience remission,drug-free remission in 35%Improvement typically delayed for months to yrs.Definite: All pts between puberty&55 yrs.Those with thymoma.Doubtful :Children & those >55 yrs.Ocular MG,MUSK ab positivity.

Immunosuppression Immediate improvement : IVIg Plasmapheresis Intermediate term: 1-3 months Glucocorticoids Cyclosporine Tacrolimus Long term: Mycophenolate mofetil /Azathioprine

Glucocorticoid therapy: Given in a single dose. Low initial dose(15-25 mg/d),increased stepwise. Until marked improvement/50-60 mg/d reached. Gradually modified to an alternate day regimen.Most common errors with steroid RX in MG: 1.Insufficient persistence 2.Too early/rapid/excessive dose tapering. 3. Lack of attention to side effects.

Myasthenic crisisExacerbation of weakness usually with respiratory

failure caused by diaphragm&intercostal muscle weakness.

Rarely occurs in properly managed persons.Anticholinesterases temporarily stopped.RX:antibiotics ,supportive measuresPlasmapheresis:usually 5 exchanges over a 10-14

day period.IVIg:usually 2 g/kg given over 5 daysBoth have intermittent benefit& are costly

Immunosuppresive drugsMycophenolate mofetil:1-1.5 g bd relative lack of side effects,high costAzathioprine :2-3 mg/kg ,beneficial effect takes 3 -6 months to

beginShould never be given AllopurinolCyclosporine/Tacrolimus:4-5mg/kg &0.1 mg/kg/d resply;nephrotoxicCyclophosphamide :reserved for refractory cases

DRUGS & MGDrugs that may exacerbate MGAntibiotics :aminoglycosides,quinolones,macrolid

esNondepolarising muscle relaxants(curare)Beta blockersLocal anaesthetics &related agentsQuinine derivativesMagnesiumPenicillamine Botulinum toxins

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