MOTOR NEURON

DISEASES

DR.PRAVEEN NAGULA

MOTOR NEURON DISEASES

Each single motor neuron and the muscle fibers it innervates constitute a MOTOR UNIT.

No .of muscle fibers in a motor unit varies.HAND,MOTION OF EYE – 3-6 muscle fibers.LEG MUSCLES – 600 muscle fibers.Group of muscle fibers (forming a motor unit )

can be intermixed in a muscle.ALL THE MUSCLE FIBERS IN A MOTOR UNIT

ARE OF SAME TYPE.

MOTOR UNIT

Based on type of muscle fibers innervated ,duration of twitch contraction

Motor units are divided intoS- slow -- small unitsFR – fast resistant to fatigueFF fast fatiguable --- large unitsRECRUITMENT of motor units follows size

principle:S muscle units – relatively slow

contraction,controlled contraction ---FR more powerful response –FF muscle units most demanding tasks..

S MUSCLE UNITS

RELATIVELY SLOW

CONTRACTION

CONTROLLED

CONTRACTION

FR MUSCLE UNITS MORE

POWERFUL

RESPONSE

FF MUSCLE UNITS

MOST DEMAN

DING TASKS

By example

STANDING

WALKING

RUNNING OR JUMPI

NG

Differ by activityIncreased activity – muscle hypertrophy –type

IIa ,IIb fibersInactivity –atrophy – type I fibers are susceptible

MUSCLE UNITS

If nerve to slow muscle

is cut,the nerve to a

fast muscle is spliced to the cut end

The fast nerve

grows and innervates

the previously

slow muscle

Muscle becomes

fast,changes in portein

isoforms,changes in myosin ATPase activity

Muscle fibers

Original delineation of ALS – charcot – CHARCOT’S disease.

Pathological apsects of disease – Joffroy,gambault

Labioglossolaryngealparalysis – progressive bulbar palsy

"Lou Gehrig's disease".

HISTORY

STEPHEN HAWKING

Amyotrophic comes from the greek language:  A- means "no", myo refers to "muscle",

and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic  atrophication of the sufferer's disused muscle tissue. 

Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located.

As this area degenerates it leads to scarring or hardening (“sclerosis") in the region.

TERMS

IntroductionHeterogenous group of neurodegenerative

disorders.Unknown etiologySelective loss of motor neurons controlling

voluntary movements.

Essentials for diagnosisWeaknessNo sensory lossNo sphincter disturbancesProgressive courseNo identifiable underlying cause

Spectrum of MNDDISORDER PRIMARY SECONDARY

UMN PRI. LATERAL SCLEROSIS

HIV,SYPHILIS,HTLV,LYME,TB

PROG.PSEUDO BULBAR PALSY

LEAD,Hg,Al,LATHYRISM,VASCULAR,TRAUMA

HER.SPASTIC PARAP.

LMN PROG.MUSCULAR ATR. AC ANTER.POLIO

S.M.A POST POLIO SYN.

P.J.B.P PARANEOPLASTIC

HUNTINGTONS

FREDERICHS

COMBINED A.M.L HYPERTHYROIDISM

HYPERPARATHYROIDIS

POST RADIATION

AMYOTROPHIC LATERAL

SCLEROSIS

AMYOTROPHIC LATERAL SCLEROSISM.C form of progressive motor neuron

disease.Prime ex. of neurodegenerative disease.Most devastating of the neurodegenerative

disorders.

EpidemiologyPrevalence 4-6/100,000Incidence-1-3/100,000Equal presentation in all racial groups20-90 years of agePeak between 50-70 yearsM:F—1.5:1Relentlessly progressiveDeath from resp. paralysisSurvival 3-5 yearsRisk factors-pesticides,smoking.

familial 5-10% 20%--SOD1 gene mutation 21q chromosome Copper , zinc dependent superoxide

dismutase gene Autosomal dominant Indistinguishable from sporadic Dynactin,senataxin Alsin –AR DYNACTIN

Pathology

HALLMARK-death of LMN ,.UMNLMN-ant.horn cells of spinal cord,bulbar

musclesUMN—layer 5 of motor cortex,descending via

pyramidal tracts.Other motor neuron disease involves only

subset of motor neurons.

BETZ CELLS

Onset-----UMN or LMN-----Involves both---absence of them ?diagnosis.

Acc of lipid pigmented—LIPOFUSCHIN.Normally seen in aged cells.Focal enlargements are frequent –SPHEROID

—acc of neurofilament proteins.Proliferation of astrocytes,microglia.Combined grey and white matter disease.Motor cells and motor fibre tracts.ATROPHY,DEGENERATION.LOSS OF MOTOR

NEURONS OF CN..

Death of the peripheral motor neurons in brainstem,spinal cord.

Denervation

Consequent atrophy of the muscle fibres

Histo chemical,electrophysiological

Early stages

Reinnervation

Less than poliomyelitis.peripheral neuropathy

Atrophy,wasting

Progressive degeneration –muscle atrophy is readily recognised in muscle biopsies and on clinical exam,---AMYOTROPHY.

Thinning of corticospinal tractsLoss of fibers in the Lateral columns—

fibrillary gliosis-LATERAL SCLEROSIS.SELECTIVITY OF NEURONAL CELL DEATH.

UBIQUITIN-marker for degeneration is seen.Nucleus of Onuf –innervates bowel ,bladder is

not involved.Max involvement in cervical spinal cordLoss of large pyramidal cells BETZ cells in

motor ,premotor cerebral cortex.Gliosis of lateral cordsNONE ARE PATHOGNOMONIC.

PathogenesisCause not well defined..Excitatory neurotransmitters.Glutamate participate in death of motor

neurons in ALS.EAAT2.SOD1—cellular defense against excitotoxicityWhen mutated—catalytic.Non neuronal cells –influences the disease

course.

CLINICAL MANIFESTATIONSVariable on motor neurons involved.Asymmetric weakness ,usually distally in one

of the limbs.Insidious onsetDevelopment of cramps with volitional

movements in early hours of morning.WeaknessWasting Atrophy

Cont.. Spontaneus twitching of motor units or

fasciculation EXTENSORS >FLEXORS in upper limbs Difficulty in chewing ,swallowing,movements of

face and tongue. Early involvement of resp.muscles—death Hyperactivity of muscle stretch reflexes Spastic response to passive movements Muscle stiffness out of proportion Exaggeration of motor expression of emotion—

weeping,laughing—pseudobulbar effect

Cont…Asymmetric—symmetricWhether UMN or LMN at onset—both laterSensory,bowel,bladder –not involved.Cognitive function,ocular motility –preservedDementia is not a component of sporadic ALSFamilial—ALS+ FRONTO TEMPORAL

DEMENTIA.

Cont… Fatigue Weight loss Wide spread muscle pains Experience fear,anxiety,depression Limb symptoms>bulbar Proximal weakness—limbs,trunks,neck Hemiplegia Spastic paraparesis Foot drop Pes cavus

Cont..Upper limb> lower limbDistal> proximalExtensor>flexorClawing of handsAsymmetric at onset

Cont..Spontaneus clonusDTR—incBabinski—postiveAbd. Reflexes –preservedBed sores are uncommon—collagenDysphagia worse for liquids > solidsChoking Flaccid dysarthriaInability to purse lips

COMPLETELY SPAREDTHE ENTIRE SENSORY APPARATUSREG. MECH. FOR CONTROL AND

COORDINATION OF MOVEMENTSCOGNITIONSEXUAL FUNCTIONOCULAR MUSCLES

Diagnosis WORLD FEDERATION OF NEUROLOGY Simultaneous inv. Of UMN,LMN PROGRESSIVE WEAKNESS EXCLUSION OF ALTERNATE DIAGNOSIS DEFINITE ALS-3 or 4 ---

bulbar,cervical,thoracic,lumbosacral 2sites—probable 1 site-possible exception –mutation in gene encoding

SOD1-21q

INVESTIGATIONSMUSCLE BIOPSYELECTROMYOGRAPHYNERVE CONDUCTION STUDIESMRIOTHER ROUTINE INVESTIGATIONS

D.DATYPICAL—only UMN or LMNInv. of neurons other than motor neuronsMotor neuronal conduction block1.cervical2.MFMN CB3.lead poisoning4.thyrotoxicosis5.recovery from poliomyelitis6. parkinsonism

TREATMENTNo treatment arrests the progression.RILUZOLE—100mg/day

Increases survival,18 monthsM.O.A- not knownDecreases glutamate release well tolerated

IGF –1Ceftriaxone—anti excitotoxicInhibitory RNA

REHABILITATIONFoot drop splintsFinger extension splintsRespiratory supportRespiratory devicesCough assist devicesGastrostomySpeech synthesizers

LMN disorders1.KENNEDY DISEASE—X LINKED

SPINOBULBAR MUSCLE ATROPHYMalesAndrogen receptor insensitivityGynaecomastiaAbsence of pyramidal tract signsSensory symptoms presentCAG

2.TAY SACHS—hexosaminidase Cerebellar atrophyAbsent spasticityDysarthria

3.SMA-5qFloppy infantInfantile—werding hoffman disease

4.MMNCB—Improved on immunoglobulins,chemotherapy.

UMN1.primary lateral sclerosis

SporadicNo fasciculationsNo denervation Selective l oss of pyramidal cells

2.familial spastic paraplegiaADRespiratory function spared

miscellaneous

1.what is a motor unit?differentiate UMN and LMN signs? Add a note on ALS ?

questions

Thank you

Thank you