**Part 1**

**Pathophysiology and Methodology** 

**1** 

Martin H. Maurer

*Germany* 

**Amyotrophic Lateral Sclerosis:** 

**An Introduction to Treatment and Trials** 

There are several synonyms for Amyotrophic Lateral Sclerosis (ALS) which include Motor Neuron Disease (MND), Charcot's disease, and Lou Gehrig's disease. The latter is named after the American baseball professional Lou Gehrig, who died of ALS in the 1940s (Miller, 2011). The symptoms of motor neuron disease (MND) have first been described by several neurologists by the mid-19th century. The French neurologist Charcot defined the nosological entity "amyotrophic lateral sclerosis" (ALS) some years later (historic aspects of ALS are reviewed in (Eisen, 2007; Mitsumoto et al., 2006; Oliveira & Pereira, 2009; Rowland, 2001;

In the present understanding, MND comprehends a spectrum of different neurodegenerative syndromes which show a common neuropathology, i. e. the progressive

These syndromes include the "classical" ALS, progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), flail arm syndrome (Vulpian-Bernhardt syndrome), flail leg syndrome, and ALS with multi-system involvement (e.g., Fronto-

The diagnosis of ALS is based on a catalogue of criteria specified by the World Federation of Neurology (www.wfneurology.org). These criteria are known as the "El Escorial" criteria, named after the Spanish historic site El Escorial. The original criteria of 1994 (Brooks, 1994; Mitsumoto, 1997) have been revised in 1998 (Brooks et al., 2000; Ross et al., 1998), which are known as the "Airlie House" criteria, named after the conference site at Warrenton, VA, U.S.A. In 2006, a consensus conference at Awaji-shima defined criteria of electromyographic and nerve conduction measurements for the diagnosis of ALS (de Carvalho et al., 2008). The clinical features comprehend the presence of (i) lower motorneuron (LMN) signs such as the loss of muscle strength, muscular atrophy, fasciculations, hyporeflexia, hypotonicity or flaccidity, or muscle cramps, in at least two limbs; (ii) upper motorneuron (UMN) signs such as extensor plantar responses, spasticity, or pathologic hyperreflexia, in at least one region (bulbar, cervical, or lumbosacral), and (iii) the progression of the disease defined as increasing symptomatic impairment by history in the same region or new regions (Ferguson

Temporal Dementia, FTD) (**Fig. 1**) (reviewed in Lillo & Hodges, 2009; Silani et al., 2011).

**1. Introduction** 

Wijesekera & Leigh, 2009)).

**2. Diagnostic criteria 2.1 Clinical features** 

& Elman, 2007).

degeneration of motor neurons.

*Dept. of Physiology and Pathophysiology, University of Heidelberg* 
