Drug Therapy for Cerebral Palsy

Cerebral palsy is non-progressive neurological condition which has a large number of associated factors. In real sense, there is no medicine as such which can cure the damage at the brain level. But a large number of medicines can be used to control or reduce the associated factors. 


Mostly associated factors which require medicines are:

• Convulsion
• Spasticity
• Involuntary movements
• Drooling 
• Constipation

Medicines to control convulsions


About one third children with cerebral palsy generally have epilepsy as one of the associated factors. 


The incidence of epilepsy is more seen in CP spastic hemiplegia followed by CP spastic quadriplegia and then CP spastic diplegia. 


The mean age of onset of seizures is 18 months. 60% have seizures onset before the age of 1 year. Children with myoclonic seizures and infantile spasms have seizure onset significantly early in life. 


All types of seizures are seen in children with cerebral palsy. 


There is increased risk of epilepsy in children with cerebral palsy if the child has any of the following associated factors: 

• Low birth weight
•  Neonatal seizure
•  Seizure during first year of life
•  Family history of epilepsy
•  Severe form of cerebral palsy
• 
  

Anticonvulsants work in the brain to suppress abnormal or hyperactive brain activity. The seizures suffered by cerebral palsy children are typically caused by overloads of "messages" sent from the brain to the nerves and muscles. Anticonvulsants help in stopping these seizures in cerebral palsy sufferers by blocking these messages. 


Most seizures that happen in cerebral palsy children are either complex-partial or tonic-clonic. Seizures are fairly common in cerebral palsy children, up to one quarter have tonic-clonic seizures and about half of people with cerebral palsy have complex-partial seizures. 


Tonic-clonic seizures usually involve a full loss of motor function. The person falls to the ground after briefly crying out. Their muscles become very tight and stiff and their hands and feet begin to twitch. Afterwards, the person may be confused for some time that can be up to a few weeks. 


A complex partial seizure doesn't involve the convulsions that a tonic-clonic seizure has. Some complex partial seizures may lead to grand mal seizures. A complex partial seizure manifests in varying degrees of severity but is usually marked by a partial lack of consciousness. This may be as slight as being forgetful, but may be as serious as to cause impaired walking. Most people who suffer a complex partial seizure do not remember the event. 


Anticonvulsants help stop these seizures in cerebral palsy children. There are different types of anticonvulsant medications available These anticonvulsants tend to limit the excessive electrical activity that occurs in cerebral palsy related seizures. There have been many successes in treating these seizures with anticonvulsants. 

Conventional antiepileptic drugs: 

Phenytoin, Phenobarbitone, Carbamazipine, Valporic acid.

Newer antiepileptic drugs: 

Oxcarbazepine, Gabapentine, Lamotrizine, Clobazam, Topramate, Levitiracetam, Zonisamide, Pregabalin, Tiagabine, Vigabatrin. 


Side effects of anticonvulsant medication include drowsiness, dizziness, irritability, confusion, vomiting, uncontrolled eye movements, gingivitis, and itching or a rash. Anticonvulsants may also interact negatively with other medications that you may be taking. 


Discontinuation of antiepileptic drugs (AED) in children with cerebral palsy can and should be practiced when possible after patients have been seizure free for at least 2 years. AED discontinuation in children with spastic hemi paresis is significantly more likely to lead to seizures relapse than children with other form of cerebral palsy. 


It is often difficult to control seizures particularly if the child has mental retardation as an associated factor. 


Neurological deficits and mental retardation are poor prognostic factors for seizure relapse after AED discontinuation. 


Polytherapy commonly used in children with cerebral palsy and seizures. 


Long term use of AED which might predispose to osteoporosis is very important issue in cerebral palsy. 


Before starting medicines for epilepsy it is necessary to diagnose the kind and severity of the seizures as some other common condition can mimic as seizures. Such as: breathe holding spell, gastro esophageal reflux, syncope, movement disorders, behavioral events and parasomnias. 

Medicines for reducing spasticity

Since cerebral palsy affects the muscular movements of its sufferers, many anti-spastic medicines for CP target these muscles. These drugs work in different ways to inhibit the muscles and nerves of the body. The muscle relaxants used for treating cerebral palsy work by stopping the muscles from contracting. These medications cease or lessen the severity of several major symptoms occurring in cerebral palsy patients. 


The three primary drugs used in treating symptoms associated with cerebral palsy are muscle relaxants. They are Diazepam, Baclofen, and Dantrolene.





Diazepam is a benzodiazepine, a type of muscle relaxant. Diazepam is also available by the name Valium. The drug acts on muscle contractions in the cerebral palsy patient, relaxing them. 


Mechanism: Increases pre-synaptic inhibition of afferent at spinal cord level. Muscle relaxation by depressing monosynaptic and polysynaptic transmission. 


Uses: It reduces generalized spasticity, hyperreflexia and painful muscle spasms. It improves sleep and reduces anxiety. 


Side effects: Sedation increased drooling, ataxia, cognitive dullness. 


Baclofen is another muscle relaxant that is used in treating symptoms of cerebral palsy. This drug is used to relax muscle spasms, which result in stiff muscles and limbs. This stiffening can cause a number of problems for the cerebral palsy children. While Diazepam works in the brain, Baclofen works in the spinal cord. The effect is that it lowers the amount of signals being sent to the muscles from the spinal cord. During Baclofen treatment, the muscle is more flexible and may respond to pediatric therapy better than before Baclofen treatment. 


Mechanism: Altered release of excitatory neurotransmitters. Depresses monosynaptic and polysynaptic transmission. 


Uses: It reduces generalized spasticity, hyperreflexia and painful muscle spasms. 


Side effects: Weakness, sedation, ataxia, nausea, impaired cognition, orthostatic hypotension, dizziness, depression etc. 

Baclofen Withdrawal Syndrome:

Sudden withdrawal may result in a withdrawal syndrome which can be potentially serious. The syndrome is characterized by seizures, hallucinations, hyperthermia, dydesthesia, pruritis, and rebound spasticity. 
Treatment of Baclofen withdrawal syndrome is immediate re-administration of Baclofen. 




Dantrolene is another drug that relaxes the muscles and may provide relief for people suffering from cerebral palsy. Dantrolene sodium lessens the calcium concentration in the muscles around the bones (skeletal muscle). The muscles become less sensitive to signals from the brain and spinal cord. The chemical workings of Dantrolene are not fully understood, but the effects are generally seen as safe. 


Mechanism: Peripheral mechanism of action is in the skeletal muscles. It has no significant effect on cardiac and smooth muscles. 


Uses: it is useful for symptomatic relief of clonuses. 


Side effects: Muscle weakness, hepato-toxicity, drowsiness






Tizanidine: Derivative: alpha-2 adrenergic agonist


Mechanism: Reduces excitatory amino acid release. Depresses polysynaptic release. 


Uses: Muscle relaxant


Side effects: Sedation, hypotension, depression, dry mouth, dizziness, hepatotoxicity. 


Another muscle relaxant called Flexeril is also sometimes used to ease the pain associated with muscle contractions. Flexeril is only prescribed for short-term use. 


There are several side effects of the muscle relaxants for cerebral palsy and the prescribing doctor should monitor them very closely. Chief among these is a dependence on the drugs, in which case the side effects of withdrawal could compound cerebral palsy symptoms. In all cases, long-term use of muscle relaxants for cerebral palsy has seen significant results in improvements of motor function, pain relief, and spasticity associated with cerebral palsy. 


Other agents: Gabapentin, Lamotrigine, Cyproheptadine, Cannabinoid like, Clonidine, etc

Medicines for reducing involuntary movements :




Anti-cholinergic can also be prescribed as part of a drug therapy for cerebral palsy. These drugs improve the body's responses and control and are usually given to patients suffering from awkward movements associated with cerebral palsy. 


Certain Dopaminergic medicine may have benefits for patients with cerebral palsy as well, though studies have only been done in their success and effects on Parkinson's patients. 


A major symptom and associated factors of cerebral palsy is abnormal movements (also known as dystonia, or dyskinesia, depending on the symptoms and other factors). Generally, these movements are due to the misfiring of chemicals in the brain that causes a slight yet uncontrollable muscle spasm. At times, or in different patients, these movements can be severely disabling. 


Two major dopaminergic drugs, which may prove to be helpful in cerebral palsy patients, are Sinemet and Artane. 


Sinemet is a dopaminergic medicine combination of two other drugs: L-dopa and carbidopa. Sinemet has been used successfully for some time in treating abnormal movements in Parkinson's children. 


Sinemet and other dopamine agonists have been long used to treat dyskinesia. Combination treatments are frequent as well, and are usually determined by the severity or frequency of the movements in the cerebral palsy child. They are usually given at an early age because there have been some frequent serious side effects in the elderly when using dopaminergic medicine for cerebral palsy or any other disease. 


These Anticholinergic and dopaminergic medicines block cholinergic nerve impulses that affect the muscles in the arms, legs, and other parts of the body. These medications help regulate muscle movement and motor function. 


Cerebral palsy children using dopaminergic medication may suffer from relapses during the treatment phase. The overall effect, however, does tend to exhibit some amount of improvement in stemming abnormal body movements. Sometimes these movements may be caused by an excess of dopamine, and sometimes by an absence of the brain chemical. These medications can help balance the dopamine levels in the brain that would result in greater motor skill ability. 


It is important to stress that long-term studies have not been done on dopaminergic medicine to treat cerebral palsy. The medications have shown significant results in similar symptoms in Parkinson's patients, however. These results have led to a greater interest in using dopaminergic medication in treatments for cerebral palsy. 

Medicines for reducing drooling : Drooling is unintentional involuntary spillage of saliva from the mouth. A major morbidity associated with cerebral palsy. It is considered as psycho-social consequences such as social stigmatization and emotional devastation for the patients and their families. 



Causes: It is commonly caused by poor oral facial and bulbar muscles control. The major contributing factors are: hyper secretion of saliva, dental malocclusion, postural problems, inability to recognize salivary spill, mouth breathing, excitement and impaired concentration, lack of sensation around the mouth. .




Complications: A lot of complications is caused due to drooling: Peri-oral chapping, dehydration, odor, social stigmatization. 



Medication: There are only a few medicines which helps reducing drooling. Anticholinergic medicines such as Glycopyrrolate and scopolamine help a little bit. 


Side effects: These medicines have lot of side effects. 

Recent development in the management of drooling

Botox injection to parotid and sub-mandibular gland. Surgical procedures such as salivary gland excision, salivary duct ligation, duct rerouting




Medicines for reducing constipation Causes: Gut dysmotility, lack of mobility, spasticity Drugs: Stool softeners, mild laxatives, diet modifications (increasing fibers, fruits, vegetables, fluids) 

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