Treatments and Prevention of Hydrocephalus

The present invention relates to the prevention or treatment of hydrocephalus. In one embodiment, the invention includes the use of one or more bioavailable folate derivatives, or salts thereof, for the prevention or treatment of hydrocephalus. Examples of more bioavailable folate derivatives that may be used include any combination of: folinic acid, tetrahydrofolate, thymidine, 10-formyltetrahydrofolate or methyltetrahydrofolate, or salts thereof. The invention also relates to a composition comprising two or more bioavailable folate derivative(s); for example, folinic acid and tetrahydrofolate.

The present invention relates to methods for preventing and treating hydrocephalus.
Hydrocephalus (HC) is a condition with multifactor aetiology resulting from an imbalance in the production and/or absorption of cerebrospinal fluid (CSF) within the head and spinal column. This leads to an accumulation of fluid within the ventricles and fluid spaces within and around the brain.

The most devastating form of HC, early-onset HC (EOHC), is that seen in foetuses and new born infants which, according to the National Institutes of Health statistics for the USA, affects 1 in 1000 live human births, making this a very significant neurological problem. Similar rates have been reported for other western countries. However rates of up to 1 in 100 have been reported in some parts of the third world (e.g. in Asia, Arabia, Persia, Africa).

Because hydrocephalus injures the brain, thought and behavior may be adversely affected. Learning disabilities are common among those with hydrocephalus, who tend to score better on verbal IQ than on performance IQ, which is thought to reflect the distribution of nerve damage to the brain. However, the severity of hydrocephalus differs considerably between individuals and some are of average or above average intelligence. Someone with hydrocephalus may have motivation and visual problems, problems with co-ordination, and may be clumsy. They may hit puberty earlier than the average. About one in four patients develop epilepsy.

Symptoms of hydrocephalus vary with age, disease progression, and individual differences in tolerance to CSF. For example, an infant's ability to tolerate CSF pressure differs from an adult's. The infant skull can expand to accommodate the build up of CSF because the sutures (the fibrous joints that connect the bones of the skull) have not yet closed. In infancy, the most obvious indication of hydrocephalus is often the rapid increase in head circumference or an unusually large head size. Other symptoms may include vomiting, sleepiness, irritability, downward deviation of the eyes (also called "sunsetting"), and seizures. Older children and adults may experience different symptoms because their skulls cannot expand to accommodate the build up of CSF.

In older children or adults, symptoms may include headache followed by vomiting, nausea, papilledema (swelling of the optic disk which is part of the optic nerve), blurred vision, diplopia (double vision), sunsetting of the eyes, problems with balance, poor coordination, gait disturbance, urinary incontinence, slowing or loss of development, lethargy, drowsiness, irritability, or other changes in personality or cognition including memory loss.

GB 802,680


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