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Amyotrophic Lateral Sclerosis

Updated : February 27, 2024





Background

Commonly also known as Lou Gehrig’s Disease, ALS is a disease which causes neurodegeneration of motor neurons. Amyotrophic lateral sclerosis does not have a single proven etiology. Instead, multiple pathways can cause very similar disease entities.

ALS has multiple patterns of onset, affecting both the lower and upper motor neurons, generally beginning with degeneration of the lower motor neurons in the proximal limbs.

ALS is an incurable and progressive disease which leads to paralysis and death. Interventions and medications can prolong life and manage symptoms for up to 10 or more years.

Epidemiology

90%-95% of ALS cases are sporadic, and the remaining have familial causes. ALS is rare worldwide, and within the US, the annual incidence of this condition is 5.2 cases per 100,000 individuals.

Individuals over the age of 40 are more susceptible to illness, and in sporadic ALS the ration of male-females is 1.3-1.5. White-skinned individuals are also more likely to be affected.

Until recently, genetic predisposition and age were the only proven risk factors for this condition, but now there’s significant evidence to suggest that another risk factors might be smoking cigarettes.

Anatomy

Pathophysiology

The pathogenesis of ALS is characterized by axonal deterioration and gliosis of axons in the lateral and anterior spinal cord columns. Eventually there’s a loss of Betz cells of the motor cortex, and motor neurons of the spinal cord.

Bunina bodies are often observed in the motor cells affected by ALS, a feature characteristic to this disease. Most cases of ALS also present with intracellular TDP-43 inclusions, a feature which pathologically links this condition to frontotemporal dementia.

Etiology

Many mechanisms have been hypothesized as the cause of sporadic ALS, but no hypothesis has been proven.

Some of the hypotheses are:

  • Free radical toxicity due to mutations of superoxide dismutase type 1 SOD1
  • Altered RNA processing which leads to prion-like self-aggregation
  • Large concentrations of glutamate
  • Surging inflammatory responses

Genetics

There are multiple genetic factors behind familial ALS, the most common of which include mutations of the SOD1 gene, and frequent expansion of the C9ORF72 gene.

Mutated SOD1 protein misfolds and accumulates, causing cellular damage and ultimately apoptosis. Both genetic abnormalities are primarily dominant autosomal traits.

Instead of having a single etiology, ALS is an etiologically complex clinical entity that results from a myriad of distinct potential preceding aberrations.

Prognostic Factors

Most patients diagnosed with ALS survive for 3-5 years, but 30% of individuals live for over 5 years, and 10%-20% for over 10 years since diagnosis.

Some of the factors which suggest a better prognosis are:

  • Higher BMI at diagnosis
  • Onset of disease at a young rage
  • Forced Vital Capacity during diagnosis
  • Higher ALS functional rating scale score

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

lactobacillus 

(Orphan)
Lactobacillus plantarum is designated for the treatment of ALS (Amyotrophic Lateral Sclerosis)



tofersen 

Indicated in patients with the above condition who have SOD1 (superoxide dismutase 1 gene)
100 mg intrathecally as a lumbar puncture
Loading dose- (1 dose every 14 days) x 3 doses
Maintenance dose- Every 28 days
tofersen does not underdo hepatic enzyme metabolism



sodium phenylbutyrate and taurursodiol 

Initial dose: one packet containing 1g taurursodiol /3g sodium phenylbutyrate orally daily for first three weeks
Maintenance dose: one packet orally twice a day



Dose Adjustments

Dosage Modifications
Hepatic impairment
Pharmacokinetics have not been studied
Mild: dose adjustment is not necessary; there have been no reports for safety issues in clinical studies.
Moderate/severe: do not use
Renal impairment
Pharmacokinetics have not been studied
Mild: dose adjustment is not necessary; there have been no reports for safety issues in clinical studies.
Moderate/severe: do not use

dextromethorphan/quinidine 

dextromethorphan/quinidine is indicated as an orphan drug for the above condition



sodium phenylbutyrate/ taurursodiol 


Indicated for Amyotrophic Lateral Sclerosis
Initial dose: one packet of 3 gm of sodium phenylbutyrate /1 gm of taurursodiol orally every day for the first 3 weeks
Maintenance dose: one packet orally two times a day



 
 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK556151/

Amyotrophic Lateral Sclerosis

Updated : February 27, 2024




Commonly also known as Lou Gehrig’s Disease, ALS is a disease which causes neurodegeneration of motor neurons. Amyotrophic lateral sclerosis does not have a single proven etiology. Instead, multiple pathways can cause very similar disease entities.

ALS has multiple patterns of onset, affecting both the lower and upper motor neurons, generally beginning with degeneration of the lower motor neurons in the proximal limbs.

ALS is an incurable and progressive disease which leads to paralysis and death. Interventions and medications can prolong life and manage symptoms for up to 10 or more years.

90%-95% of ALS cases are sporadic, and the remaining have familial causes. ALS is rare worldwide, and within the US, the annual incidence of this condition is 5.2 cases per 100,000 individuals.

Individuals over the age of 40 are more susceptible to illness, and in sporadic ALS the ration of male-females is 1.3-1.5. White-skinned individuals are also more likely to be affected.

Until recently, genetic predisposition and age were the only proven risk factors for this condition, but now there’s significant evidence to suggest that another risk factors might be smoking cigarettes.

The pathogenesis of ALS is characterized by axonal deterioration and gliosis of axons in the lateral and anterior spinal cord columns. Eventually there’s a loss of Betz cells of the motor cortex, and motor neurons of the spinal cord.

Bunina bodies are often observed in the motor cells affected by ALS, a feature characteristic to this disease. Most cases of ALS also present with intracellular TDP-43 inclusions, a feature which pathologically links this condition to frontotemporal dementia.

Many mechanisms have been hypothesized as the cause of sporadic ALS, but no hypothesis has been proven.

Some of the hypotheses are:

  • Free radical toxicity due to mutations of superoxide dismutase type 1 SOD1
  • Altered RNA processing which leads to prion-like self-aggregation
  • Large concentrations of glutamate
  • Surging inflammatory responses

There are multiple genetic factors behind familial ALS, the most common of which include mutations of the SOD1 gene, and frequent expansion of the C9ORF72 gene.

Mutated SOD1 protein misfolds and accumulates, causing cellular damage and ultimately apoptosis. Both genetic abnormalities are primarily dominant autosomal traits.

Instead of having a single etiology, ALS is an etiologically complex clinical entity that results from a myriad of distinct potential preceding aberrations.

Most patients diagnosed with ALS survive for 3-5 years, but 30% of individuals live for over 5 years, and 10%-20% for over 10 years since diagnosis.

Some of the factors which suggest a better prognosis are:

  • Higher BMI at diagnosis
  • Onset of disease at a young rage
  • Forced Vital Capacity during diagnosis
  • Higher ALS functional rating scale score

lactobacillus 

(Orphan)
Lactobacillus plantarum is designated for the treatment of ALS (Amyotrophic Lateral Sclerosis)



tofersen 

Indicated in patients with the above condition who have SOD1 (superoxide dismutase 1 gene)
100 mg intrathecally as a lumbar puncture
Loading dose- (1 dose every 14 days) x 3 doses
Maintenance dose- Every 28 days
tofersen does not underdo hepatic enzyme metabolism



sodium phenylbutyrate and taurursodiol 

Initial dose: one packet containing 1g taurursodiol /3g sodium phenylbutyrate orally daily for first three weeks
Maintenance dose: one packet orally twice a day



Dose Adjustments

Dosage Modifications
Hepatic impairment
Pharmacokinetics have not been studied
Mild: dose adjustment is not necessary; there have been no reports for safety issues in clinical studies.
Moderate/severe: do not use
Renal impairment
Pharmacokinetics have not been studied
Mild: dose adjustment is not necessary; there have been no reports for safety issues in clinical studies.
Moderate/severe: do not use

dextromethorphan/quinidine 

dextromethorphan/quinidine is indicated as an orphan drug for the above condition



sodium phenylbutyrate/ taurursodiol 


Indicated for Amyotrophic Lateral Sclerosis
Initial dose: one packet of 3 gm of sodium phenylbutyrate /1 gm of taurursodiol orally every day for the first 3 weeks
Maintenance dose: one packet orally two times a day



https://www.ncbi.nlm.nih.gov/books/NBK556151/