The ALS

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, characterized by progressive dysfunction and death of motor neurons in the primary cortex, cortico-spinal tracts, brainstem and spinal cord. As a consequence of neural degeneration, a muscular paralysis develops that prejudice the use of hands, arms and legs, and hampers speech, swallowing and breathing. ALS usually progresses rapidly with 2-to 3-year average survival in bulbar onset patients and 3- to 5-year average survival in those with spinal onset disease. The cause of ALS is unknown although diverse theories for its pathogenesis have been proposed, including oxidative stress, excitotoxicity, mitochondrial dysfunction, apoptosis, alterations in growth factor signaling and abnormal protein/neurofilaments aggregation.

The incidence of ALS in Italy is approximately 2-3 cases/100.000/year with a point prevalence  of about 7 cases/100.000.

ALS is also known as a motor neuron disease or Maladie de Cahrcot after the French neurologist that was the first to describe the disease in 1860. In North America, the condition is often referred to as a Lou Gehrig’s Disease after the baseball player that was the first known case diagnosed with ALS and died from it in 1941, at age of thirty-seven.
Almost 150 years after the disease was first described by Jean Martin Charcot, the causes of ALS remain fundamentally unknown. Rare cases of familial ALS are known to arise from mutations in the gene encoding superoxide dismutase Cu/Zn (SOD1), an enzyme with an anti-oxidant function.  Several hypotheses have focused on the role of glutamate in motor neuron degeneration, others considered the impact of environmental factors such as exposure to toxic or infectious agents, or a lifestyle habits including diet, occupational risks or traumas. In this regard, recent observation of the increased frequency of ALS among Italian professional soccer players, in particular well-known cases such as that of ex Milan and Fiorentina striker Stefano Borgonovo, has evoked a considerable interest in the media and in the scientific community. Various possibilities were considered in order to explain the causative agent of ALS among soccer players, including also drugs and doping, dietary supplements, pesticides used on the playgrounds, head and spinal cord trauma history; nevertheless, no universal agreement have been achieved. Likely ALS/MND is multi-factorial disease triggered by a complex interaction of environmental factors and potentially susceptible gene alterations.
Typically, ALS is of insidious onset, with initial symptoms that are often overlooked and can considerably vary from one patient to another. The common feature is a progressive muscle weakness and atrophy that affects all voluntary movements. Approximately two thirds of ALS patients present with symptoms related to focal muscle weakness in the upper and lower limbs (spinal form of the disease or typical ‘Charcot ALS’). Other symptoms may involve speech impairment and chewing and swallowing disturbances. Besides muscle weakness and wasting, the patients may notice fasciculation and cramps. The involvement of respiratory muscles is usually evidenced by shortness of breath after only slight exertion and the coughing difficulties.
In case of bulbar onset ALS, patients usually present with dysarthhria of speech and swallowing difficulties.
Overall, the disease determines a progressive and irreversible loss of motor functions enabling scheletric muscle control, speech and swallowing, with the consequent paralysis that extends and eventually causes respiratory insufficiency leading first to the need for ventilation support and, ultimately, to death due to a respiratory failure and pulmonary complications.
ALS typically does not alter patient’s cognitive, sensorial and sexual functions; also bladder and bowel control are usually preserved.
No test is currently available for quick and certain diagnosis of ALS. Diagnosis is based on the exclusion of ALS mimics intending the presence of clinical findings of combined UMN and LMN signs that can not be explained by any other disease process evident upon electrophysiological imaging, CSF or serological studies. In fact, the mean diagnostic delay from symptom onset to a diagnosis of ALS has been reported to be between 8 to 15 months. Ongoing studies are aimed at identification of biomarkers that would enable efficient detection and treatment of the disease.
Currently, no efficient therapeutic treatment is available for ALS. Only FDA-approved drug is Riluzole, a glutamate release inhibitor, that has a modest effect on prolonging life and delaying disease progression in ALS patients