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n_mnd

motor neurone disease (MND)

Introduction

  • a group of progressive neuronal degenerative diseases with generally poor prognosis
  • when one talks on MND, they are usually referring to ALS which is a type of motor neuron disease

Patterns of weakness

  • Asymmetric distal weakness without sensory loss
    • ALS, PLS, PMA, MMA
  • Symmetric weakness without sensory loss
    • PMA, PLS
  • Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement)
    • ALS, PBP, PLS

Amyotrophic lateral sclerosis (ALS)

  • aka Lou Gehrig's disease
  • progressive degeneration of motor nerve cells in the brain (upper motor neurons) and spinal cord (lower motor neurons) associated with impaired folding of neuronal intracellular proteins resulting in mSOD1 toxicity and TDP‐43 pathology
  • in 2021 it was reported than a new compound NU-9 was able to reduce this protein abnormal folding, improve mitochondrial and endoplasmic reticulum function and reverse the neuronal degeneration over 90 days in mice1)
  • most develop it between 40-70yrs, especially 60-70yrs but can occur younger
  • similar incidence as multiple sclerosis (MS) and accounts for 5 of every 100,000 adult deaths
  • no cause found in 90% of cases hence are regarded as “sporadic”, 5% have a clear AD genetic cause with:
    • 25-40% of the familial form of ALS in adults is caused by a defect in a gene known as “chromosome 9 open reading frame 72,” or C9ORF72
    • 10-12% of the familial cases having mutations in the gene for the enzymes superoxide dismutase 1 (SOD1) or copper zinc superoxide dismutase
  • Ubiquilin-2 (UBQLN2)2) gene mutations result in loss of UBQLN2 which reduces expression of ATP6v1g1, a critical subunit of the ATPase pump that regulates vacuolar acidification and is required for the maturation of autophagosomes.3)
  • there is a suggestion that dietary exposure to a blue-green algae toxin known as β-N-methylamino-L-alanine (BMAA) may be causative and that a diet of L-serine may partly prevent it, at least in animal models 4)

Classification of ALS

Classical ALS

  • 2/3rds of cases of ALS
  • “people first experience awkwardness when walking or running or even tripping over or stumbling may be experienced and often this is marked by walking with a “dropped foot” which drags gently on the ground. Or if arm-onset, difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock may be experienced”

Progressive Bulbar Palsy (PBP)

  • 25% of cases of ALS; mainly causes a LMN bulbar palsy
  • early cases may have:
    • difficulty with pronunciations, particularly lateral consonants (linguals) and velars
    • drooling of saliva
    • gagging, choking, aspiration of food and saliva
    • 25% develop widespread symptoms common to ALS
  • later, loss of gag reflex, tongue fasciculations, and inability to protrude the tongue occur
  • some may develop pseudobulbar palsy and emotional changes
  • death, usually from aspiration pneumonia, usually occurs within 1-3 yrs of onset of disorder

Progressive Muscular Atrophy (PMA)

  • rare, mainly affects LMN neurones

Familial

  • 5-10% of cases of ALS

Primary Lateral Sclerosis (PLS)

  • rarest form of ALS; mainly affects UMNs

Diagnosis of ALS

  • Body segments for the diagnostic criteria are: bulbar, cervical, thoracic and lumbar myotomal regions
  • Lower motor neuron (LMN) findings include muscle atrophy and fasciculations
  • Upper motor neuron (UMN) findings include hyperreflexia, spasticity, and muscle spasm
  • bulbar (LMN) features are:
    • difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea)
    • wasted tongue with fasciculations
    • absent gag reflex
    • nasal speech
  • pseudobulbar (UMN) features are:
    • labile emotion with pseudobulbar affect, problems in word fluency, decision-making, and memory
    • small, tight, spastic tongue which cannot be protruded and lies on the floor of the mouth
    • monotonous, slurred, high-pitched, ‘Donald Duck’ dysarthria”
    • increased jaw jerk

World Federation of Neurology (WFN)

  • clinically definite:
    • UMN and LMN signs in at least 3 body segments
  • clinically probable:
    • UMN and LMN signs in at least 2 body segments with some UMN signs in a segment above the LMN signs
  • Clinically probable, laboratory-supported ALS:
    • UMN and LMN signs in 1 segment or UMN signs in 1 region coupled with LMN signs by electromyography (EMG) in at least 2 limbs
  • Clinically possible ALS:
    • UMN and LMN signs in 1 body segment, UMN signs alone in at least 2 segments, or LMN signs in segments above UMN signs
  • Clinically suspected ALS:
    • Pure LMN syndrome with other causes of LMN disease adequately excluded
n_mnd.txt · Last modified: 2021/02/24 21:25 by gary1