Amyotrophic Lateral Sclerosis - Overview.pptx

Motor neuron disease

1. Amyotrophic Lateral Sclerosis - Overview Hatem Shawky Ahmed Assistant Lecturer of Neurology Cairo University 2024 Adapted from Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases By Aaron Izenberg , MD CONTINUUM) 2023;29(5, PERIPHERAL NERVE AND MOTOR NEURON DISORDERS

2. MND – Variants Injury of the cell body of the motor neuron – either UMN or LMN or both

3. MND – Variants Isolated UMN : POC Primary lateral sclerosis Hereditary Spastic Paraplagia Age 50 Childhood to 7 th decade Inheritance None - Acquired AD mainly Clinical picture Gradually progressive bilateral leg followed by arm spasticity and stiffness and spastic dysarthria . Pseudobulbar palsy and pseudobulbar affect. Repeated falls, imbalance rather than weakness Paraplegia : Spasticity > weakness Minimal UL , Bulbar , sphincter Other rare finidings : Optic atrophy, Cataracts Ataxia Dementia Extrapyramidal manifestations Investigations MRI : Cortical (precentral gyrus) atrophy EMG : No denervation TMS : Delayed central motor conduction TMS : minimally delayed central motor conduction Progression Fast Slow , gradual

4. MND – Variants Isolated LMN : POC Progressive Muscle Atrophy Spinal Muscle Atrophy Age men below the age of 50 year Types: Birth to >30 years Inheritance None AR mainly Clinical Picture Wasting and weakness. UL > LL but rare/late bulbar. Rare Bladder Rare Dementia Anxiety and depression are common Symmetric Proximal weakness . LL > UL. Lost DTR. +/- Respiratory Treatment Supportive and similar to the treatment for ALS but better prognosis Survival Motor Neuron (SMN)1,2 genes delivery or modification e.g. Nusinersen Progression Slow

5. SMA

6. ALS - Epidemiology Global incidence 2 per 100,000 people/year prevalence is 5 per 100,000 people Men : Women = 1.5 :1 60 - 75 years, although the disease can present from the second to beyond the ninth decade of life. Risk Factors Age Family history Smoking Other: Higher levels of physical activity and participation in sports associated with concussion Exposure to heavy metals, electromagnetic fields, and toxins such as pesticides Military service Global, regional, and national burden of motor neuron diseases 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology VOLUME 17, ISSUE 12, P1083-1097, DECEMBER 2018

7. The incidence of MND is 5.7% in patients with cervical spondylotic myelopathy

8. Clinical picture – Limbs Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease .Lauren B Elman, MD Leo McCluskey , MD, MBE Colin Quinn, MD . Literature review current through: Dec 2023

9. Clinical picture – Bulbar

10. Clinical picture – Axial

11. Clinical picture – Respiratory

12. Clinical picture – Cognitive Nonmotor manifestations of ALS 50 % of patients with ALS will have some degree of cognitive or behavioral dysfunction on neuropsychological assessment, 15 % of patients will develop frontotemporal dementia (FTD ). 15% of patients initially diagnosed with FTD will develop features of ALS. ALS-FTD Genetic susceptibility Disinhibition, apathy , and loss of empathy

13. Diagnosis

14. Diagnosis : El Escorial Criteria Redler , R.L., & Dokholyan , N.V. The Complex Molecular Biology of Amyotrophic Lateral Sclerosis ( als ). UMN and LMN where the LMN is rostral

15. Diagnosis : Revised El Escorial Criteria

16. Diagnosis : Awaji Shima

17. Diagnosis : Gold Coast Criteria ALS is No longer a clinical diagnosis

18. Diagnosis : Gold Coast Criteria ALS is No longer a clinical diagnosis

19. ALS : D. Diagnosis

20. ALS : D.Diagnosis Weakness > wasting

21. ALS : D.Diagnosis

22. Investigations

23. Investigations

24. Investigations

25. Treatment Supportive measures Associated symptoms Life threatening Respiratory and feeding support Disease Modifying Measures Staging and Scoring

26. Supportive treatment

27. Supportive treatment Management algorithm for respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). FVC = forced vital capacity; H 2 O = water; MIP = maximal inspiratory pressure; NIV = noninvasive ventilation; Pco 2 = partial pressure of carbon dioxide; SNIP = sniff nasal inspiratory pressure; SVC = slow vital capacity. Modified with permission from Shoesmith C, et al, CMAJ. 77 © 2020 Joule Inc.

28. Treatment - DMD Riluzole ( Rilutek ) Edaravone ( Radicava ) sodium phenylbutyrate and tauroursodeoxycholic acid TUDCA ( Relyvrio ) MoAction inhibitor of glutaminergic excitotoxicity free-radical scavenger Reducing endoplasmic reticulum stress and mitochondrial dysfunction Approved since 1995 IV : 2017 Oral : 2022 2022 Efficacy 6-19 m survival over placebo reduction in decline (33%) in ALSFRS-R over placebo 4.8 m survival over placebo Duration Beyond 48 weeks : no proven benefit Dose 50 mg TAB BID IV: 60 mg (2vials) IV infusion PO : 105 mg (5 mL suspension) daily for 2 w, followed by a 2w drug-free period. Oral : Initial dosage:1 packet daily for the first 3 weeks maintenance dosage: 1 packet twice daily Side effects GIT upset, dizziness, increased Liver enzymes (need 3m testing) and fatigue. Neutropenia injection site reactions, gait disturbance, headaches GIT,URT, Salt and water retention, Hyperbillirubinemia

29. Treatment - DMD Other DMDs include Stem cell therapy Gene Therapy

30. Scoring 2. The revised ALS Functional Rating Scale (ALSFRS-R) 1 . The Short Form (SF-12) Health Survey 3 . The ALS Assessment Questionnaire (ALSAQ-5 Score ) 4. The CareGiver Burden Scale (CGBS ) The ALS CARE program https://www.outcomes-umassmed.org/als/sf12.aspx

31. Scoring (ALSFRS-R)

32. Scoring (ALSFRS-R)

33. Staging The King’s staging four categories based on the sequential involvement of body regions and the need for respiratory or swallowing support. The ALS Milano-Torino staging based on ALSFRS-R scores. Patients progress through stages 0 to 5 based on the number of functional domains involved (with stage 5 indicating death ). The Personalized European Network for the Cure of ALS (ENCALS) survival model Clinical predictors: including age at onset, time to diagnosis, rate of ALSFRS-R progression, FVC, bulbar onset, revised El Escorial criteria definite ALS diagnosis, FTD, and C9orf72 expansion, categorize patients into five survival groups ranging from very short (predicted median survival, 17.7 months) to very long (predicted median survival, 91.0 months).

34. MND – Variants Isolated UMN : Primary lateral sclerosis Isolated UMN degeneration (but some patients presenting will subsequently develop LMN manifestations, as an UMN-predominant form of ALS ) Age of Gradually progressive bilateral leg followed by arm spasticity and stiffness and spastic dysarthria . Pseudobulbar palsy and pseudobulbar affect. Repeated falls , and patients may report imbalance rather than weakness. Investigations MRI : Cortical atrophy of precentral gyrus EMG : No denervation TMS : delayed central motor conduction diagnostic criteria probable PLS : isolated UMN involvement between 2-4 years from symptom onset definite PLS : beyond 4 years . D.D. : hereditary spastic paraparesis (HSP), bilateral lower limb spasticity and weakness . But in contrast to PLS, HSP shows: Bladder dysfunction or sensory manifestations Rarely Affected upper limb and bulbar muscles. Strong familial pattern More gradual progression

35. MND – Variants Isolated LMN : Progressive Muscular Atrophy Isolated LMN involvement ( however, 20 % of patients will ultimately develop UMN features ) Similar to PLS, progressive muscular atrophy is typically associated with more prolonged survival. Compared with ALS, median survival in PMA was higher (48 versus 36 months) Kim WK, Liu X, Sandner J, Pasmantier M, Andrews J, Rowland LP, Mitsumoto H Neurology. 2009;73(20):1686.