M O T O R N E U R O N D I S E A S E SPresentation Transcript
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 into S- slow -- small units FR – fast resistant to fatigue FF fast fatiguable --- large units RECRUITMENT of motor units follows size principle: S muscle units – relatively slow contraction,controlled contraction ---FR more powerful response –FF muscle units most demanding tasks..
Differ by activity Increased activity – muscle hypertrophy –type IIa ,IIb fibers Inactivity –atrophy – type I fibers are susceptible MUSCLE UNITS
Original delineation of ALS – charcot – CHARCOT’S disease. Pathological apsects of disease – Joffroy,gambault Labioglossolaryngealparalysis – progressive bulbar palsy "Lou Gehrig's disease". HISTORY
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
Introduction Heterogenous group of neurodegenerative disorders. Unknown etiology Selective loss of motor neurons controlling voluntary movements.
Essentials for diagnosis Weakness No sensory loss No sphincter disturbances Progressive course No identifiable underlying cause
Spectrum of MND
AMYOTROPHIC LATERAL SCLEROSIS
AMYOTROPHIC LATERAL SCLEROSIS M.C form of progressive motor neuron disease. Prime ex. of neurodegenerative disease. Most devastating of the neurodegenerative disorders.
Epidemiology Prevalence 4-6/100,000 Incidence-1-3/100,000 Equal presentation in all racial groups 20-90 years of age Peak between 50-70 years M:F—1.5:1 Relentlessly progressive Death from resp. paralysis Survival 3-5 years Risk factors-pesticides,smoking.
20%--SOD1 gene mutation
Copper , zinc dependent superoxide dismutase gene
Indistinguishable from sporadic
Pathology HALLMARK-death of LMN ,.UMN LMN-ant.horn cells of spinal cord,bulbar muscles UMN—layer 5 of motor cortex,descending via pyramidal tracts. Other motor neuron disease involves only subset of motor neurons.
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 Histochemical,electrophysiological Early stages Reinnervation Less than poliomyelitis.peripheral neuropathy
Progressive degeneration –muscle atrophy is readily recognised in muscle biopsies and on clinical exam,---AMYOTROPHY. Thinning of corticospinal tracts Loss of fibers in the Lateral columns—fibrillarygliosis-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 cord Loss of large pyramidal cells BETZ cells in motor ,premotor cerebral cortex. Gliosis of lateral cords NONE ARE PATHOGNOMONIC.
Pathogenesis Cause not well defined.. Excitatory neurotransmitters. Glutamate participate in death of motor neurons in ALS. EAAT2. SOD1—cellular defense against excitotoxicity When mutated—catalytic. Non neuronal cells –influences the disease course.
CLINICAL MANIFESTATIONS Variable on motor neurons involved. Asymmetric weakness ,usually distally in one of the limbs. Insidious onset Development of cramps with volitional movements in early hours of morning. Weakness Wasting Atrophy
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—symmetric Whether UMN or LMN at onset—both later Sensory,bowel,bladder –not involved. Cognitive function,ocular motility –preserved Dementia is not a component of sporadic ALS Familial—ALS+ FRONTO TEMPORAL DEMENTIA.
Wide spread muscle pains
Cont.. Upper limb> lower limb Distal> proximal Extensor>flexor Clawing of hands Asymmetric at onset
Cont.. Spontaneus clonus DTR—inc Babinski—postive Abd. Reflexes –preserved Bed sores are uncommon—collagen Dysphagia worse for liquids > solids Choking Flaccid dysarthria Inability to purse lips
COMPLETELY SPARED THE ENTIRE SENSORY APPARATUS REG. MECH. FOR CONTROL AND COORDINATION OF MOVEMENTS COGNITION SEXUAL FUNCTION OCULAR MUSCLES
WORLD FEDERATION OF NEUROLOGY
Simultaneous inv. Of UMN,LMN
EXCLUSION OF ALTERNATE DIAGNOSIS
DEFINITE ALS-3 or 4 ---bulbar,cervical,thoracic,lumbosacral
D.D ATYPICAL—only UMN or LMN Inv. of neurons other than motor neurons Motor neuronal conduction block 1.cervical 2.MFMN CB 3.lead poisoning 4.thyrotoxicosis 5.recovery from poliomyelitis 6. parkinsonism
TREATMENT No treatment arrests the progression. RILUZOLE—100mg/day Increases survival,18 months M.O.A- not known Decreases glutamate release well tolerated IGF –1 Ceftriaxone—anti excitotoxic Inhibitory RNA
REHABILITATION Foot drop splints Finger extension splints Respiratory support Respiratory devices Cough assist devices Gastrostomy Speech synthesizers