As with many diseases, even those of non-neurological origin, ALS often presents with non-specific symptoms. This process can take place over several years and cannot be stopped at the moment.
The disease progresses silently and manifests itself when the progressive loss of motor neurons exceeds the compensatory capacity of the surviving motor neurons.
The initial symptoms of ALS can be quite varied in different people, often involving muscle weakness or stiffness as early symptoms. One person may have trouble grasping a pen or lifting a coffee cup, while another person may experience a change in vocal pitch when speaking. ALS is typically a disease that involves a gradual onset.Symptoms can begin in the muscles that control speech and swallowing or in the hands, arms, legs or feet. Not all people with ALS experience the same symptoms or the same sequences or patterns of progression. Progression, in fact, is not always a straight line in an individual either. It is not uncommon to have periods lasting weeks to months where there is very little or no loss of function. Progression of weakness, wasting and paralysis of the muscles of the limbs and trunk as well as those that control vital functions such as speech, swallowing and later breathing generally follows.
The rate at which ALS progresses can be quite variable from one person to another. Although the mean survival time with ALS is three to five years, many people live five, 10 or more years.
When the breathing muscles become affected, ultimately, people with the disease will need permanent ventilatory support to assist with breathing.
Since ALS attacks only motor neurons, it does not compromise internal organs (heart, liver, kidneys) and the sense of sight, touch, hearing, taste and smell are not affected. The sexual functions are also preserved. For many people, muscles of the eyes and bladder are generally not affected.
Unfortunately, ALS is a difficult disease to diagnose. Diagnosis requires several medical investigations and in each patient the progression can be evaluated only through periodic neurological controls (every 2-3 months), since there is no one test or procedure to ultimately establish the diagnosis of ALS with high diagnostic and prognostic accuracy.
It is through a clinical examination and series of diagnostic tests, often ruling out other diseases that mimic ALS, that a diagnosis can be established. The diagnosis of ALS is therefore made by exclusion: an experienced neurologist requires medical investigations and clinical evaluations repeated over time in a diagnostic path that involves neurological tests and instrumental examinations. In Italy there are specialized and accredited clinical centers for the diagnosis of ALS able to certificate and define the therapeutic plan of care (D.M. 279/2001). Please visit AISLA website for more information (in italian): http://www.aisla.it/old-site/centri.php?sezioni=1
Considerable progress has been made in the field of instrumental diagnostics. While traditional methods of Magnetic Resonance Imaging (MRI) are mainly used to exclude ALS-like pathologies, several MRI techniques, such as voxel-based morphometry, have made it possible to identify the cerebral changes induced by the pathology. Also the use of Magnetic Resonance Spectroscopy (H-MRS), a technique still under development, is able to potentially give some diagnostic support, being a non-invasive technique able to investigate the presence of chemicals in a given volume of the brain in vivo. In addition, Positron Emission Tomography (PET) has also recently shown the potential ability to accurately diagnose the disease and it will be hopefully soon available.
A recent work by the German-Italian research group led by Markus Otto of the University of Ulm and Federico Verde of the University of Milan and of the Italian Auxological Institute confirmed the validity of a blood test, which is therefore not invasive and repeatable over time, that can be used to diagnose ALS. This test measures neurofilaments, the proteins that make up the “scaffolding” of nerve cells such as motor neurons. During the course of the disease, in fact, the motor neurons degenerate, releasing fragments in the bloodstream that can thus be measured and constitute an excellent tool to diagnose early neurodegenerative diseases such as ALS. This discovery therefore pave the way to a faster and less invasive diagnosis of disease.
At the moment, the diagnostic workup includes most, if not all, of the following procedures:
- Electrodiagnostic tests including electomyography (EMG) and nerve conduction velocity (NCV), which allows the evaluation of the function of nerves and peripheral muscles
- Nuclear Magnetic Resonance (NMR), in particular for the study of the pyramidal system and PET (Tomography ad Emission of Positrons), which allows to study the functional metabolism of different brain areas.
- Muscle and/or nerve biopsy
- Blood and urine studies
- Prognostic factors in ALS: A critical review. Adriano Chiò et al. Amyotroph Lateral Scler. 2009 OctDec; 10(5-6): 310–323.
- The epidemiology and treatment of ALS: Focus on the heterogeneity of the disease and critical appraisal of therapeutic trials. Ettore Beghi et al. Amyotroph Lateral Scler. Jan 2011; 12(1): 1–10)