Cramps
Muscle cramps are a frequent though nonspecific early symptom of ALS. Factors that promote them are strong physical exertion, cold, sleep deprivation, alcohol, nicotine and water and electrolyte deficiency. However, cramps also occur spontaneously. They represent a nonspecific reaction of the muscle and spinal reflex arc to different stimuli. The cause is assumed to be hyperexcitability of terminal axon endings. Regular physical training and gymnastic exercises along with prevention of venous congestion by elevating the legs have a preventive effect. Acute treatment consists of passive stretching of the affected muscle or application of heat. If they persist, medical treatment with membrane stabilising medications, magnesium, quinine and aminophylline (e.g. Limptar®), phenytoin (e.g. Phenytoin®), carbamazepine (e.g. Tegretol®) or low dose antispasmodic agents such as tizanidine (e.g. Sirdalud®) or baclofen (e.g. Lioresal®) is recommended.

Fasciculations
Fasciculations are perceived by patients as troublesome relatively seldom. Carbamazepine (e.g. Tegretol®) can be used therapeutically in low dosages. Experience has shown that the intensity of the fasciculations becomes less in the course of the disease than at the start of the ALS.

Paresis
Special physiotherapy to treat ALS has not so far been developed. The methods of physical therapy in ALS are derived from broad experience in related neurological diseases, which are also associated with paresis or spasticity. The greatest experience derives from stroke rehabilitation. Regular physiotherapy exercise of moderate intensity is recommended (2 to 3 times per week). It is useful to make contact with a physical therapy practice that has experience in treating neurological diseases, e.g. after stroke, multiple sclerosis or Parkinson's disease. It is an advantage if the physical therapy practice has experience with ALS but this is not essential. Physiotherapy is the basis of the treatment of paresis in ALS. At the same time, it must be stressed that physiotherapy serves to relieve symptoms but cannot prevent progression of the disease. The aims of physiotherapy are to preserve the function of still intact musculature and prevent contractures, thrombosis and pneumonia. If residual movement is still present, isometric muscle training and exercises against resistance have proven effective. Apart from their effect on movement, they also promote muscle perfusion.

If spasticity predominates, physiotherapy methods (e.g. the Bobath method) should be employed. Individual exercises should be performed daily by the patient independently following training. In the case of major paresis, passive mobilisation to prevent contractures (shortening of tendons) is of great importance. The use of therapeutic aids (e.g. splints), positioning and transport aids (stair lifts, bath tub lifts, care beds etc.) and mobility aids (rollators, risers, wheelchairs etc.) requires specialised information, counselling and provision.

Spasticity
Severe spasticity requiring treatment is relatively rare in ALS. The basic aim of antispastic therapy is to reduce the increased muscle tension while preserving a certain postural tone. Excessive drug therapy leads to intensification of the muscle weakness. Physiotherapy based on neurophysiology is the method of choice for treating spasticity. When the symptoms are marked, independent treatment at home on an exercise trainer is useful. Treatment is targeted especially at spastically induced pain and early limitations of movement (contractures). Suitable medications are baclofen (Lioresal®) and tizanidine (Sirdalud®).

Drug treatment of spasticity is problematic in many cases as high doses of medication are necessary to achieve a reduction of the muscle tension. In this case, adverse drug effects of the medications baclofen and tizanidine can occur, consisting of fatigue, disorders of balance and depression. If the spasticity is painful and at the onset of contractures treatment with botulinum toxin is an option that is indicated in selected patients. Botulinum toxin is a medication that is injected into the spastic musculature and leads to relaxation of the treated muscle groups. An advantage of this treatment option is that the effect of the medication is limited regionally to the site of injection so that fatigue and slowing are not to be expected. Unwanted limpness of the injected muscles, which can lead to an increase of the muscle weakness, can be a disadvantage. Following injection of botulinum toxin the muscle relaxant effect lasts for 2 to 3 months. Overall, spasticity is the predominant symptom for few patients. In this case, the treatment options of physiotherapy, spasmolytic therapy and botulinum toxin should be used according to individual criteria.

Dysarthria
The causes of the speech disorder (dysarthria) include degeneration of motor neurons in the brainstem (bulbar dysarthria), spastic influences (pseudobulbar dysarthria) and speech dependent shortness of breath (dyspnoea). Speech therapy, consisting of buccofacial exercises and breathing and speech exercises to use the residual function of the speech apparatus, should begin even in the initial stage. In the advanced stage, provision of communication aids is required. Writing and letter slates are simple aids, which require adequate function of the limbs. With progression of the paresis, use of electronic means of communication and control is indicated. Important advantages of electronic communication means (e.g. LightWriter or Spok21) include rapid adjustment to a further increase in the degree of disability in the course of the disease, storage of standard linguistic situations and speech emission (e.g. on the telephone). Control technology allows improved control of the patient’s immediate environment (control of lights, window opening, TV, CD player, page turning devices etc.). When there is complete loss of motor limb functions, the preserved eye muscle functions can be used to control special communication devices. In this area, very advanced and user friendly devices are now available (e.g. EyeGaze, MyTobii, Quick Glance etc).

Dysphagia
The cause of the disorder of chewing and swallowing (dysphagia) is degeneration of motor neurons in the brain stem. The consequences of the dysphagia are prolonged meals, reduction of oral food intake and the tendency to aspirate saliva and food components. By aspiration is meant the uncontrolled entry of saliva and food into the airways. The possible consequences include acute shortness of breath (dyspnoea) due to obstruction of the airways and inflammation of the bronchial system (bronchitis) and lungs (pneumonia).

As soon as dysphagia starts, speech therapy with functional swallow training is useful. The patients learn important compensation strategies (making the swallow units smaller, deliberate coughing after swallowing etc.). When there is an increase in the dysphagia with weight loss, frequent aspiration and infections of the upper airways together with prolongation of meals, a decision on placement of a feeding tube must be made (percutaneous endoscopic gastrostomy = PEG).
PEG is an alternative feeding method that circumvents oral food intake. In a small operation, a thin plastic tube can be placed in the stomach through the abdominal wall using minimally invasive endoscopic methods. Just a few days after the operation, a liquid diet containing energy, vitamins and minerals can be given through the PEG tube.

The operation is performed in a few minutes in conjunction with a stomach camera (gastroscopy). The PEG is inserted during a short hospital admission for about 5 days in a neurological or internal medicine department. The operation is performed in an endoscopy department and takes less than 1 hour. For this purpose, patients are transported to the department only for the duration of the procedure. After placement of the PEG, a short course of antibiotic treatment and observation in hospital for a few days are necessary. In this time the first liquids can be given through the PEG tube. Actually building up the diet begins again in the home environment. After being discharged home, training is provided by a specially trained outpatient nurse or dietician. Handling the PEG tube is most important. During the further course of the disease, the PEG entry site and diet therapy are checked by the diet nurse. This postoperative care by outpatient nursing staff is already organised by the clinic.

Sialorrhoea
N acetylcysteine (e.g. ACC®) or ambroxol (e.g. Mucosolvan®) can be used if the mucus is thickened. Adequate fluid intake should always be ensured.

Inhaled therapy with secretolytic agents (Mucosolvan®, Bromhexin Inhalat®) can also be used. ALS is not associated with increased production of saliva. Nevertheless, saliva flowing from the mouth (sialorrhoea) is a frequent and troublesome symptom of ALS. The salivation arises because of the dysphagia and the inability to swallow the produced saliva. Because of the additional weakness of the facial, oral and neck muscles, patients suffer from increased leakage of saliva from the mouth. Various therapeutic medications are available: amitriptyline (e.g. Saroten®), imipramine (e.g. Tofranil®), scopolamine patches (e.g. Scopoderm TTS®) and atropine (e.g. Belladonnysat drops, Atropin sulfuricum AWD tablets®). Medication induced reduction of saliva production or pharmacological alteration of the viscosity of the mucus has limited effectiveness. If the oral medications are ineffective, botulinum toxin (Dysport®, Botox® or Xeomin®) can be injected locally into the parotid (salivary) gland. This requires 4 6 injections in front of the ear and at the back of the cheek on both sides of the face with a fine needle. The injection is well tolerated by most patients and is not experienced as uncomfortable. Botulinum toxin has specific pharmacological properties that reduce saliva production by the injected gland for 2 to 3 months. The injection treatment can produce a reduction of 30 to 50% in daily saliva production. The effect of the botulinum toxin therapy lasts 2 to 3 months. As the effect wears off, repeated injections at 3 month intervals are usually necessary. Because of variations in human anatomy, not all salivary glands are readily accessible to injection treatment so that in some ALS patients, treatment with botulinum toxin does not lead to the desired success. In this case, radiotherapy of the parotid gland can be considered. This requires referral to a specialist centre with a radiotherapy department and experience with treatment of sialorrhoea. Radiotherapy of sialorrhoea must be decided in the individual case and is not yet an established method of treatment in ALS. If the sialorrhoea persists despite attempts at drug treatment, it is possible to use a suction pump to remove the saliva from the mouth. This is very effective in reaching saliva from the front sections of the throat and from the mouth. The limits of the method consist of mucus production in the posterior parts of the throat and dependency on another person if the affected patient has paresis of the arms. If sialorrhoea is severe and the requirement of a carer to perform suction is met, a suitable suction pump can be prescribed medically.

Pathological laughing/crying
The symptom of pathological laughing/crying consists of uncontrolled laughing/crying that does not have a situational and emotional basis. It is a frequent component of the pseudobulbar syndrome in ALS. The cause is considered to be frontal disinhibition, lesion of dopaminergic neurons and disinhibition of the striatum or brainstem. Different medical treatment options are available. There have been positive experiences with serotonin reuptake inhibitors e.g. citalopram (Cipramil ®) or fluvoxamine (Fevarin®) in high doses. If these are not effective, treatment with L dopa (e.g. D: Nacom®, Madopar®) or lithium (e.g. Quilonum®) is possible.

Respiratory failure
Weakness of the respiratory and accessory respiratory muscles is a regular symptom of advanced ALS. The respiratory dysfunction causes different symptoms, which can be summarised as chronic hypoventilation (reduced breathing) syndrome. The reduction in breathing capacity is usually the limiting factor for life expectancy and is the most common cause of death in ALS. The symptoms of alveolar hypoventilation are night time sleep disorders, states of agitation and tachycardia, morning headache, nightmares, daytime drowsiness and concentration disorders. Lung function parameters (e.g. vital capacity), the blood gases and nocturnal oxygen saturation provide additional information. An acute deterioration of respiratory function is often the result of infections of the airways.

Breathing exercises and medication with secretion dissolving drugs (e.g. bromhexine, N acetylcysteine etc.) are useful for preventing infections. Mask ventilation is a possibility for treating the symptoms of chronic hypoventilation. Nocturnal mask ventilation is indicated especially when typical symptoms are present including nocturnal sleep disorders, morning headache, memory disorders, depression or daytime drowsiness. Repeated analysis of the arterial blood gases is also performed. If the symptoms can be attributed to existing respiratory dysfunction with CO2 accumulation (hypercapnia), a mask is fitted and nocturnal ventilation for 6 to 8 hours is begun. If the treatment leads to an improvement of the clinical symptoms and of the blood gas parameters, continued use as intermittent home nocturnal ventilation is attempted. Currently, about 15% of all ALS patients decide on nocturnal intermittent mask ventilation. If the respiratory insufficiency progresses, tracheotomy (an opening in the windpipe) and mechanical ventilation are possible in principle. Deciding on mechanical ventilation has wide reaching medical and psychosocial consequences for patients. Tracheostomy assisted breathing is performed in fewer than 10% of ALS patients. Long term ventilation uses predominantly home ventilation technology under nursing supervision by outpatient ventilation teams.