Congenital neurology disorders:New treatments at the threshold?

Diseases related to the central nervous system cause various deformities. And congenital neurological disorders can bring heavy burden on the child and parents. Therefore, early diagnosis and treatment is essential to save the crippling effects caused by neurological diseases.

Dr Asma Mohd Yousuf

Each day during the nine months of pregnancy, a mother prays for a healthy child. There are many hopes and dreams attached with the birth of a child and any congenital anomaly can shatter these dreams. Neurological congenital malformations are not rare. Many infants are born with abnormalities like neural tube defect, hydrocephalus, microcephaly and spinal defect. There is high mortality and morbidity due to neurological birth defects.           

Dr Anurag Krishna

Pointing out the common neurological defects, Dr Anurag Krishna, Director, Paediatrics and Paediatric Surgeon, Max Healthcare, New Delhi, says, “The common congenital neurological diseases are neural tube defects like spina bifida, meningocele, myelomeningocele, encephalocele, etc. The other common diseases are hypoxic ischaemic encephalopathy secondary to perinatal asphyxia, neonatal seizures, intraventricular haemorrhage especially in preterms, congenital viral and bacterial infections resulting in meningitis. The rare ones are neurological manifestations secondary to metabolic and degenerative diseases, neurocutaneous syndromes and epilepsy syndromes.”

Further, providing statistical information on congenital neurological anomalies, Dr Krishna says, “Congenital neurological diseases come with high morbidity and mortality rates. Perinatal asphyxia has 15-45 per cent morbidity and upto 30 per cent mortality. Neural tube defects carry a mortality risk of 15 per cent in developed countries and the risk is high in developing countries such as India. It is very difficult to access prevalence due to lack of reporting in our country. However, the prevalence of perinatal asphyxia is around 2 per cent of live births in the US. Neural tube defects have a prevalence of 1 in 2000 live births and intraventricular haemorrhage occurs in 5 per cent of newborns <35 weeks of gestation.”

Dr N K Venkataramana

However, Dr N K Venkataramana, Vice-Chairman and Chief Neurosurgeon, BGS Global Hospitals, Bengaluru, admits, “Overall the incidence of these anomalies is coming down due to the better prenatal diagnostic facilities, prenatal care and good maternal nutrition. Because of early diagnosis and appropriate treatment, the mortality has significantly reduced. However, the morbidity still persists at a lower level. The incidence is 1-3 per 1000 live births. Incidence varies depending on the geographical regional factors and consanguinity.”

Causative factors

Dr P N Renjen

A large number of congenital neurological problems are possible in the brain and spinal cord. Many of these are related to genetic abnormalities, while the others are related to formative problems. In agreement, Dr P N Renjen, Senior Consultant, Neurology, Indraprastha Apollo Hospitals, Delhi, says, “Genetics plays a very important role in the occurrence of these diseases. Some genetically inherited diseases include diseases of the brain, muscles and nerves.”

Taking this topic further, Dr Krishna informs, “Neurocutaneous syndromes, such as neurofibromatosis, tuberous sclerosis and Sturge-Weber disease are familial. Sporadic gene mutations cause disorders of neuronal migration, such as lissencephaly, schizencephaly and holoprosencephaly. Various syndromes with Central Nervous System (CNS) involvement have a genetic abnormality such as Aicardi syndrome, hydrocephalus secondary to aqueductal stenosis and genetic epileptic syndromes.”

Other factors responsible for these congenital neurological disorders include the pre-natal condition of the mother, drug intake during pregnancy, consanguinity, birth injuries and pre-existing congenital problems in the family. Dr Krishna adds, “Extreme prematurity can cause intraventricular haemorrhage and hydrocephalus. Perinatal asphyxia resulting from hypoxic ischaemic encephalopathy, and mental retardation with developmental delay are other common pathologies found in India. Various viral infections like toxoplasmosis, cytomegalovirus & herpes simplex as well as bacterial infections from Escherichia coli, Klebsiella & pneumococcus are still predominant in our country resulting in meningitis and seizures.”

Diagnosis, prognosis and management

An early diagnosis of congenital neurological disorders can be done, especially for neural tube defects. Prenatal screening, including an ultrasound and certain blood tests will help in diagnosing these diseases, giving a prognosis to the family and deciding on further line of treatment after birth, in terms of surgery.

Avers Dr Venkataramana, “Now-a-days it is routine to have prenatal ultrasound scan around the 15th week of gestation to identify anomalies. If there is a suspicion, then amniotic fluid analysis, genetic counselling, metabolic screening and foetal MRI are various modalities for diagnosis. Majority of the abnormalities can be diagnosed except some genetic and metabolic syndromes. After the suspicion or diagnosis, counselling will be performed by a team of specialists to discuss the viability of the child, expected disability and to advise parents accordingly.”

Dr A Goel

Agrees Dr A Goel, Neuro Surgeon, S L Raheja (a Fortis associate) Hospital, Mumbai, “Computer-based investigations have remarkably changed the diagnostic scenario in neurological problems. Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) have revolutionised the investigations in the last two decades. Foetal scanning can also be informative regarding gross problems in the foetus. Evaluation and understanding of these problems can sometimes lead to attempts towards premature termination of pregnancy or surgery in utero.”

Medical termination of pregnancy is offered to mothers less than 20 weeks of gestation after a proper antenatal counselling if the foetus has a major congenital malformation. Postnatal, various tertiary care hospitals are now well equipped with state-of-the-art neonatal Intensive Care Units (ICUs) to take care of the newborns with congenital defects and diseases. But there is not much awareness in rural India on the availability of the tests and facilities. However, Internet and news channels have certainly helped in increasing awareness especially in metropolitan cities.

Generally, the prognosis in neurological diseases depends on the type of anomaly, how early it is diagnosed and how well it is treated. In addition, rehabilitation of the child, motivation of parents and family, and development of complications will also influence the prognosis. In agreement, Dr Krishna says, “As far the prognosis is concerned, obviously the outcome is bad in metabolic and degenerative neurological diseases as there is still no cure for majority of them. With the availability of specific anticonvulsants, the outcome is better in epileptic cases. The improvement in neonatal surgeries and post-operative care of surgical cases such as neural tube defects has certainly improved the growth and development of these patients, but the morbidity and mortality remains high.”

Adds, Dr Goel, “Neurological diseases, if diagnosed timely and treated appropriately, the long term outcome in many of these congenital diseases is satisfying. However, there are numerous congenital anomalies, each having treatment specific to it. There is no uniform treatment for congenital disorders in neurology. Surgical procedures like shunt surgery, fixation surgery and repair surgery have helped patients. Other procedures like foetal surgical treatment is yet not popular or in vogue. In India, such a treatment is not done. Robotic surgery is very premature to talk about as it is still in its infancy, and again such surgeries are not yet established in India. Also, stem cell therapy has not shown any significant promise in the treatment of any neurological problem.”

Role of stem cells

Dr Arvin Faundo

Stem cells are widely believed to have significant potential in the treatment of human diseases. They also offer new opportunities for the treatment of incurable neurological diseases. Emphasising on the role of stem cells in congenital malformation, Dr Arvin Faundo, Group Medical Affairs Manager, Cordlife Group, says, “Microcephaly is a congenital malformation of the nervous system, and there is no specific treatment for this condition, except supportive care. Some patients with microcephaly have been associated with Fanconi anaemia. The latter is the result of a defect in the ability of a person for Deoxyribonucleic acid (DNA) repair. It is manifested by bone marrow failure and eventual development of cancers. Definitive treatment involves bone marrow transplantation with a suitable donor. After the first successful cord blood transplant for Fanconi anaemia in 1988, efforts are now placed on improving outcomes for these patients.”

He further informs, “A relatively common neurologic condition that may benefit from stem cell therapy is cerebral palsy. This refers to disorders manifesting with developmental disabilities in body movements. It may be related to damage to the motor centres of the infantile brain before, during or after childbirth.” Elaborating further, Dr Faundo adds, “The extrapolated incidence in India is about two million children. Management of the most severe cases requires life-long supportive therapy. Following reports of physical and psychosocial improvements in patients, who received stem cell infusions, several clinical trials are underway to evaluate the benefit of autologous cord blood stem cells.”

The medical community is optimistic on the role of stem cell therapy to finally provide the much needed cure for such devastating diseases. Dr Venkataramana feels, “Stem cells seem to be promising in promoting regeneration, thereby repairing the damaged areas. This will definitely reduce the disability. Stem cells have immunomodulatory qualities and may be beneficial in modifying disease profile. However, a lot more needs to be understood regarding the application of stem cell therapy to these congenital diseases affecting the brain and spinal cord.”

Market analysis

As per ‘Neurology Devices, India’ – a report by GlobalData, Cerebrospinal Fluid (CSF) management is the fastest growing category within the neurology devices market in India. It showed a growth rate of 18.4 per cent between 2003 and 2010 and is forecast to grow by 11.2 per cent between 2010 and 2017.

The report also mentions that the neurology devices market in India is dominated by interventional neurology, followed by neurostimulation devices market categories. The neurology devices market growth is driven by neurostimulation devices, interventional neurology and CSF management market categories, which grew above the average neurology devices market growth during 2003-2010, and is expected to continue the same trend during 2010-2017.

Interventional neurology was the largest category in the neurology devices market in 2010 in India with $18.9 million in revenues. The interventional neurology category grew at a Compounded Annual Growth Rate (CAGR) of 16.5 per cent from 2003 to 2010. Neurostimulation devices were the second largest category with revenues of $12.0 million in 2010.

As per the report, interventional neurology is expected to be the largest category in the neurology devices market in 2017 in India with $41.0 million in revenues. The interventional neurology category is expected to grow at a CAGR of 11.7 per cent from 2010 to 2017. Neurostimulation devices are expected to be the second largest category with revenues of $26.8 million in 2017. However, interventional neurology would continue to be the largest category in terms of units sold in the neurology devices market in India with a CAGR of 10.8 per cent from 2010 to 2017. The volume sales in this category are expected to be 88,931 units in 2017.

Hence…

Although the market for neurological diagnostic equipment and interventional neurology appears bright, there is still a lot of research to be done to come up with therapies that can cure such congenital anomalies. Dr Venkataramana says, “Several trials in the world are conducted to prevent the anomaly by nutritional supplements, for example, fortification of folic acid to prevent spina bifida. However, for early treatment, several trials are conducted to treat the anomaly in utero in order to prevent further implications and complications. It is now a separate speciality called foetal neurosurgery.”

Further, he adds, “Future challenges will be to identify all the causative factors for these anomalies and understand the genetic factors in order to prevent the complications by altering these factors. Gene therapy and regenerative medicine like stem cells can play a significant role in future in reducing the disability caused by congenital neurological disorders.”

There are many diseases that go undetected or are ignored in our country, of which congenital disorders form a significant portion. However, with improved and readily available diagnostic methods, today it is possible to detect these anomalies right at the foetal stage. This enables the treating physician to decide on an appropriate treatment plan or take necessary measures to save both the child as well as the parents from stress and trauma such disorders bring along. Therefore, awareness of these conditions and diagnostic methods among the parents-to-be is of paramount importance in order to take necessary precautions to avoid the onset of such debilitating disorders even before the conception of the baby.