Motor neuron diseases involve the degeneration and death of motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common and devastating form of motor neuron disease. It is characterized by the progressive loss of both upper and lower motor neurons, leading to muscle weakness, atrophy, and eventually paralysis. There is no cure for ALS, though some treatments can prolong survival.

1. MOTOR NEURON DISEASES

2. DR.PRAVEEN NAGULA MOTOR NEURON DISEASES

3. 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

4. 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..

8. By example

9. Differ by activity Increased activity – muscle hypertrophy –type IIa ,IIb fibers Inactivity –atrophy – type I fibers are susceptible MUSCLE UNITS

10. Muscle fibers

11. Original delineation of ALS – charcot – CHARCOT’S disease. Pathological apsects of disease – Joffroy,gambault Labioglossolaryngealparalysis – progressive bulbar palsy "Lou Gehrig's disease". HISTORY

12. STEPHEN HAWKING

13. 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

14. Introduction Heterogenous group of neurodegenerative disorders. Unknown etiology Selective loss of motor neurons controlling voluntary movements.

15. Essentials for diagnosis Weakness No sensory loss No sphincter disturbances Progressive course No identifiable underlying cause

16. Spectrum of MND

17. AMYOTROPHIC LATERAL SCLEROSIS

18. AMYOTROPHIC LATERAL SCLEROSIS M.C form of progressive motor neuron disease. Prime ex. of neurodegenerative disease. Most devastating of the neurodegenerative disorders.

19. 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.

21. 20%--SOD1 gene mutation

22. 21q chromosome

23. Copper , zinc dependent superoxide dismutase gene

24. Autosomal dominant

25. Indistinguishable from sporadic

26. Dynactin,senataxin

27. Alsin –AR

30. BETZ CELLS

32. 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..

33. 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

34. Atrophy,wasting

35. 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.

36. 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.

37. 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.

38. 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

40. EXTENSORS >FLEXORS in upper limbs

41. Difficulty in chewing ,swallowing,movements of face and tongue.

42. Early involvement of resp.muscles—death

43. Hyperactivity of muscle stretch reflexes

44. Spastic response to passive movements

45. Muscle stiffness out of proportion

48. Weight loss

49. Wide spread muscle pains

50. Experience fear,anxiety,depression

51. Limb symptoms>bulbar

52. Proximal weakness—limbs,trunks,neck

53. Hemiplegia

54. Spastic paraparesis

55. Foot drop

57. 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

58. COMPLETELY SPARED THE ENTIRE SENSORY APPARATUS REG. MECH. FOR CONTROL AND COORDINATION OF MOVEMENTS COGNITION SEXUAL FUNCTION OCULAR MUSCLES

60. Simultaneous inv. Of UMN,LMN

61. PROGRESSIVE WEAKNESS

62. EXCLUSION OF ALTERNATE DIAGNOSIS

63. DEFINITE ALS-3 or 4 ---bulbar,cervical,thoracic,lumbosacral

64. 2sites—probable

65. 1 site-possible

67. 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

68. 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

69. REHABILITATION Foot drop splints Finger extension splints Respiratory support Respiratory devices Cough assist devices Gastrostomy Speech synthesizers

70. LMN disorders 1.KENNEDY DISEASE—X LINKED SPINOBULBAR MUSCLE ATROPHY Males Androgen receptor insensitivity Gynaecomastia Absence of pyramidal tract signs Sensory symptoms present CAG

71. 2.TAY SACHS—hexosaminidase Cerebellar atrophy Absent spasticity Dysarthria 3.SMA-5q Floppy infant Infantile—werdinghoffman disease 4.MMNCB— Improved on immunoglobulins,chemotherapy.

72. UMN 1.primary lateral sclerosis Sporadic No fasciculations No denervation Selective l oss of pyramidal cells 2.familial spastic paraplegia AD Respiratory function spared

73. miscellaneous

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

75. Thank you

77. Thank you