Academic Neurosurgeon, Neuroscientist, Christian humanitarian
Author: Professor Tony Magana
Professor Tony Magana is Head of the Department of Neurosurgery, School of Medicine, College of Health Sciences at Mekelle University in Mekelle, Ethiopia. He directs a neurosurgery residency and training program as well as neuroscience research.
Ethiopia is facing a growing crisis in infant meningitis compounded by a false reliance on the power of antibiotics to treat the problem without definitive diagnosis and follow up.
A growing problem
As you may know north eastern Africa including Ethiopia is part of the so-called “meningitis belt” with the highest rates of bacterial meningitis in the world. Just a couple a months ago I was attending a meeting with Ministry of Health with the new five pediatric neurosurgery centers of excellence in Ethiopia where a new growing epidemic of chronic meningitis seen throughout the country was discussed. Over the past year we are seeing more and more cases of infants on an almost daily basis presenting with progressive hydrocephalus who have diagnostic cerebrospinal fluid consistent with chronic meningitis. Our average census is 5 to 8 in hospital all the time whereas a few years ago it was only one or two. Many of these children have hospitalizations of 12 weeks or more. Many have died and many are left with significant cerebral disability which could have been prevented by earlier intervention and appropriate treatment lengths.
While this epidemic seems to be worsening, Dr. Abreha (Head of Pediatrics and Pediatric Neurologist at Mekelle University) and myself are concerned that deficiencies in facilities and procedures within the medical system may be contributing to it. Unfortunately throughout Ethiopia almost no lumbar punctures are now done to diagnose meningitis. A sample inquiry of pediatric residents and interns found that 75% of them had never done a lumbar puncture. Additionally many clinics and hospitals do not even have lumbar puncture trays. A false sense of security exists that powerful antibiotics given a short period time can will solve the problem
Secondly, the lack of ability to process or even receive an CSF specimen for analysis beyond 5 PM forces the treating physicians to start treatment without first obtaining a culture which is against world wide standard of culture first then start treatment. This seems very contrarian to the frequent theme of the pharmacy and laboratory professionals in Ethiopia that there is abuse of antibiotics.
A key analysis is determining the glucose, protein, and cell count in cerebrospinal fluid. Dr. Abreha recently gave a sample of tap water to the laboratory to be tested on the automated machine and it diagnosed multiple WBC consistent with meningitis. The equipment supplied to Ethiopian hospital is not capable of accurate diagnosis. Technicians can do manual counts but these are time consuming and labor intensive. This inaccuracy has greatly impaired our ability to determine if patients are infection free which they must be before they can undergo definitive treatment for hydrocephalus which is a ventriculoperitoneal shunt.
Thirdly, around the world there is much controversy about for how long antibiotic treatment should be given ranging from 10 days to 21 days. The problem is that partially treated meningitis patients who have not been cleared from the infection often do not have fever, meningeal signs, or other clinical findings except hydrocephalus. Many infants are briefly seen for nonspecific fever and receive short courses of antibiotics in Ethiopia without specific diagnosis being made and without adequate follow up. Many of these children we believe are harboring these low grade chronic infections leading to their late appearance at Ayder Comprehensive Specialized Hospital. This creates a great dilemma as these children often require treatment of intravenous powerful expensive antibiotics from 21 days to in excess of six weeks or more until the infection is cleared by the demonstration of two negative cultures off antibiotics and normal cell counts. In addition in order for the shunt to work the protein has to be less than 150 mg/dl. Failure to diagnose an active residual infection before a shunt placement will only aggravate the infection leading to shunt removal and complications.
The treasure and future of Ethiopia is in her children. Meningitis appropriately treated early and followed can have a very low morbidity and disability outcome. The current situation if not acted upon will result in increasing medical costs, increasing disability, and increasing infant death which could be prevented with simple directed community and institutional action.
Recommended Course of Action 1. Immediate upgrade of laboratory ability in hospitals to receive CSF specimens 24 hours a day for culture, gram stain, sensitivity. 2. Training of interns and residents in performing lumbar puncture and making sets available 3. Institute an Ethiopian wide policy of obtaining CSF before starting antibiotics. Children with seizures, lethargy, focal deficit, or signs of increased intracranial pressure would be emergently sent to a referral hospital for CT Scan or if possible if they have an open fontanelle undergo an head ultrasound locally to rule out mass before lumbar puncture. 4. Make sure all children treated for meningitis undergo follow-up and that a repeat lumbar puncture is done after treatment. This may seem over kill but given the crisis happening it is the only way to prevent these chronic cases. 5. Funding of community service, public education, and research projects on this vital issue in cooperation with the regional health bureaus. 6. Training of health officers, nurses, and general practitioners in proper diagnosis, evaluation, treatment, and referral of children with meningitis and hydrocephalus.
The Department of Neurosurgery at Ayder Comprehensive Specialized Hospital of Mekelle University treats over 1000 significant head injuries every year including performing an average of 2.5 operations per day. All patients should undergo standard multiple trauma resuscitation and assessment by Advanced Trauma Life Support Guideline.
Since 2015 the Department of Neurosurgery at Mekelle University has instituted a standard head injury protocol (now revised in 2019) for the assessment and treatment of children and adults at Ayder Comprehensive Specialized Hospital based in part upon the local settings of Northern Ethiopia and the international guidelines including that of the Brain Trauma Foundation
Intracranial pressure monitoring is not economically feasible in Ethiopia but we are developing research protocols to look at optic nerve sheath diameter by serial ultrasound in the near future.
Adults Initial Assessment The management of patients with a head injury should be guided by clinical assessments and protocols based on the Glasgow Coma Scale and Glasgow Coma Scale Score.
Indications for referral to hospital Adult patients with any of the following signs and symptoms should be referred to an appropriate hospital for further assessment of potential brain injury:
1. GCS<15 at initial assessment (if this is thought to be alcohol related observe for two hours and refer if GCS score remains<15 after this time)
post-traumatic seizure (generalized or focal) focal neurological signs
2. signs of a skull fracture (including cerebrospinal fluid from nose or ears,
hemotympanum, boggy hematoma, post auricular or periorbital bruising)
3. loss of consciousness
4. severe and persistent headache
5. post-traumatic amnesia >5 minutesrepeated vomiting (two or more occasions)
6. retrograde amnesia >30 minutes
7. high risk mechanism of injury (road traffic accident, significant fall)
coagulopathy, whether drug-induced or otherwise.
Indications for head CT scan Immediate CT scanning should be done in an adult patient who has any of the following features:
1. eye opening only to pain or not conversing (GCS 12/15 or less)
2. confusion or drowsiness (GCS 13/15 or 14/15) followed by failure to improve within at most one hour of clinical observation or within two hours of injury (whether or not intoxication from drugs or alcohol is a possible contributory factor)
3. base of skull or depressed skull fracture and/or suspected penetrating injuries
4. a deteriorating level of consciousness or new focal neurological signs
full consciousness (GCS 15/15) with no fracture but other features, eg
— severe and persistent headache
— two distinct episodes of vomiting
5. a history of coagulopathy (eg warfarin use) and loss of consciousness, amnesia or any neurological feature.
CT scanning should be performed within eight hours in an adult patient who is otherwise well but has any of the following features:
1. age>65 (with loss of consciousness or amnesia)
2. clinical evidence of a skull fracture (eg boggy scalp haematoma) but no clinical features indicative of an immediate CT scan
3. any seizure activity
4. significant retrograde amnesia (>30 minutes)
5. dangerous mechanism of injury (pedestrian struck by motor vehicle, occupant ejected from motor vehicle, significant fall from height) or significant assault (eg blunt trauma with a weapon).
In adult patients who are GCS<15 with indications for a CT head scan, scanning should include the cervical spine.
Indications for admission to hospital An adult patient should be admitted/observed to hospital if:
1. the level of consciousness is impaired (GCS<15/15)
2. the patient is fully conscious (GCS 15/15) but has any indication for a CT scan (if the scan is normal and there are no other reasons for admission, then the patient may be considered for discharge)
3. the patient has significant medical problems, eg anticoagulant use
4. the patient has social problems or cannot be supervised by a responsible adult.
Referral to neurosurgical unit A patient with a head injury should be discussed with a neurosurgeon:
1. when a CT scan in a general hospital shows a recent intracranial lesion
when a patient fulfills the criteria for CT scanning but facilities are unavailable
2. when the patient has clinical features that suggest that specialist neuroscience assessment, monitoring, or management are appropriate, irrespective of the result of any CT scan.
3. All salvageable patients with severe head injury (GCS score 8/15 or less) should be
4. transferred to, and treated in, a setting with 24-hour neurological ICU facility.
Children Initial assessment
Great care should be taken when interpreting the Glasgow Coma Scale in the
under fives and this should be done by those with experience in the management of the young child. Pediatric Glasgow Coma Scale and Scoring (for use in patients under five years of age)
Indications for referral to hospital In addition to the indications for referral of adults to hospital, children who have sustained a head injury should be referred to hospital if any of the following risk factors apply:
1. clinical suspicion of non-accidental injury
2. significant medical co-morbidity (eg learning difficulties, autism, metabolic disorders)
3. difficulty making a full assessment
4. not accompanied by a responsible adult
5. social circumstances considered unsuitable.
Indications for head CT scan Immediate CT scanning should be done in a child (<16 years) who has any of the following features:
1. GCS≤13 on assessment in emergency department
2. witnessed loss of consciousness >5 minutes
3. suspicion of open or depressed skull injury or tense fontanel
4. focal neurological deficit
5. any sign of basal skull fracture.
CT scanning should be considered within eight hours if any of the following features are present (excluding indications for an immediate scan):
1. presence of any bruise/swelling/laceration >5 cm on the head
2. post-traumatic seizure, but no history of epilepsy nor history suggestive –of reflex anoxic seizure
–amnesia (anterograde or retrograde) lasting >5 minutes
–clinical suspicion of non-accidental head injury
–a significant fall
–age under one year: GCS<15 in emergency department assessed by
–personnel experienced in paediatric GCS monitoring
–three or more discrete episodes of vomiting
–abnormal drowsiness (slowness to respond).
If a child meets head injury criteria for admission and was involved in a high speed road traffic accident, scanning should be done immediately
Indications for admission to hospital Children who have sustained a head injury should be admitted to hospital if any of the following risk factors apply:
1. any indication for a CT scan
2. suspicion of non-accidental injury
3. significant medical co-morbidity
4. difficulty making a full assessment
5. child not accompanied by a responsible adult
6. social circumstances considered unsuitable.
Referral to neurosurgical unit A patient with a head injury should be discussed with a neurosurgeon:
1. when a CT scan in a general hospital shows a recent intracranial lesion
2. when a patient fulfills the criteria for CT scanning but facilities are
3. when the patient has clinical features that suggest that specialist
neuroscience assessment, monitoring, or management are appropriate,
irrespective of the result of any CT scan.
4. All salvageable patients with severe head injury (GCS score 8/15 or less) should be transferred to, and treated in, a setting with 24-hour neurological ICU facility.
In hospital care All medical and nursing staff involved in the care of patients with a head injury should be trained and competent in the use and recording of the Glasgow Coma Scale. The GCS should not be used in isolation and other parameters should be considered along with it, such as:
–pupil size and reactivity
–respiratory rate and oxygen saturation
–unusual behavior or temperament or speech impairment.
Family members and friends should be used as a source of information.
Observations should be recorded on a chart
Children <3 years old who have sustained a head injury are particularly difficult to evaluate and clinicians should have a low threshold of suspicion for early consultation with a specialist pediatric unit.
Children who are admitted should be under the care of a multidisciplinary team that includes a pediatric trained doctor experienced in the care of children with a head injury.
Children should be observed on a children’s ward.
The risk of rapid deterioration is greatest in the first six hours after injury and then decreases. If the patient is admitted on the first day of the injury then repeat evaluation every few hours is indicated if high risk factors such as high energy injury, Glasgow coma scale < 15, or focal neurological deficit is present.
Medical staff should assess the patient on admission to the ward and should re-assess the patient at least once within the next 24 hours. Assessment should include: examination for the GCS, neck movement, limb power, pupil reactions, all cranial nerves and signs of basal skull fracture.
Any of the following examples of neurological deterioration should prompt urgent re-appraisal by a doctor:
–the development of agitation or abnormal behavior
–a sustained decrease in conscious level of at least one point in the motor or verbal response or two points in the eye opening response of the GCS score
–the development of severe or increasing headache or persisting vomiting
new or evolving neurological symptoms or signs, such as pupil inequality or
asymmetry of limb or facial movement.
If re-assessment confirms a neurological deterioration, many factors need to be evaluated but the first step is to ensure the airway is clear, and that oxygenation and circulation are adequate.
Clinical signs of shock in a patient with a head injury should be assumed, until proven otherwise, to be due to hypovolemia caused by associated injuries.
Whilst an intoxicating agent may confuse the clinical picture, the assumption that deterioration or failure to improve is due to drugs or alcohol must be resisted.
If systemic causes of deterioration such as hypoxia, fluid and electrolyte imbalance, or hypoglycemia can be excluded, then resuscitation should continue according to accepted trauma protocols.
After traumatic brain injury, agitation may be a sign of neurological deterioration, hypoxia, electrolyte disturbance, drug/alcohol withdrawal, or seizures. Medical evaluation should be done in conjunction with pharmacological therapy for behavior.
Therapeutic Goals and Interventions
Systolic BP < 90 mm Hg and O2 Saturation < 90% should be avoided.
Mannitol in doses of 0.25gram/kg to 1.0gram/kg may reduce ICP. Our usual regimen is to give an initial dose of 1.0 gram/kg and the start 0.25mg/kg every 8 hours. The dose can be increased up to 1.0 gram/kg and frequency up to every 6 hours as needed. It is most useful as a temporizing measure such as to treat a patient suspected of having a mass lesion which may be surgical while preparing that patient for surgery. It is most effective in bolus doses rather constant infusion which may be repeated every 6 hours. Most of the world wide experience deals with controlling intracranial pressure which is being monitored. It should not be a part of routine head injury management. Side effects of hypotension, increases in size of intraparenchymal brain hemorrhage, and kidney dysfunction may occur.
The use of mannitol for head injury treatment in developing countries without ICP monitoring has not been well studied.
1. Salvageable Head Injury with GCS 8 or less.
2. Deterioration from GCS > 8 to less for three days as above
3. Pre-operative .25gram/kg to 1.0gram/kg dose for suspected or known mass lesion. May be repeated intra-operatively.
4. Post-operative management of cerebral edema
Enteral feeding should be begun by 72 hours after injury. Hyperglycemia should be avoided as increased intracellular lactic acidosis can worsen brain injury.
Seizures and Seizure Prophylaxis
Prophylactic anticonvulsants does not reduce late seizure development or improve outcomes. However we face an unusual situation in Ethiopia where there are no intravenous anticonvulsants. We have had experiences of a few patients in the past few years whose developed early onset post traumatic seizures which where difficult to control while we were waiting for oral phenytoin to be absorbed which typically takes about 24 hours. Therefore we are changing our previous recommendation to start phenytoin or carbamezipine in any patient with an abnormal brain finding on CT Scan of the brain and continue for 7 days.
Anticonvulsant treatment indications:
Phenytoin use according to body mass and age for a seizure in the first few days and continued for one week.
Craniotomy for intraparenchymal lesion (evacuation of hemorrhagic contusion or lobectomy) or if a dural tear is discovered such as for depressed fracture
Routine single dose of Ceftriaxzone 1 gm IV on call for adults and 50mg/Kg in children for closed head injuries requiring surgery.
Single dose of periprocedural antibiotics for intubation only unless the patient has signs of aspiration pneumonia already present.
Low molecular weight heparin is contraindicated in the presence of acute head injury. If there is no large hematoma (intraparenchymal) then generally should wait at least five days before beginning low dose heparin 5,000 units BID or low molecular weight heparin Graduated stockings or pneumatic compression stockings if available are appropriate.
Profound hypercarbia may increase ICP and profound hypocarbia may decrease cerebral perfusion. Hyperventilation is to be avoided in the first 24 hours after injury. Temporary mild hyperventilation pre-operatively or intra-operatively may be used.
There is no sound scientific evidence supporting the use of steroids for head injury.
Under special circumstances such as post-operative swelling or diffuse cerebral swelling in a viable patients in consultation with neurosurgical staff pentobarbital at 3mg/kg/ hour may be given for up to three days to attempt to control brain swelling. Patients who have bilateral dilated pupils and decreased brain stem function are not candidates for this treatment modality.
Most of the studies suggest post-traumatic meningitis can be treated similar to community acquired bacterial meningitis with Ceftriaxzone 1 gm Q12h in adults. If no response is seen consideration can be given to adding Vancomycin and Meripenum for resistant organism. In our experience most patients respond to a 10 day course of Ceftriaxzone. Consideration can be given to performing a lumbar puncture for culture and sensitivity if CT Scan shows no mass effect. If staph aureus is identified then treatment should be extended for 21 days duration.
Surgical Management Guidelines
Note: The clinical progression of the patient must always be considered strongly in decision to do surgery or treat conservatively. Lesions affecting the temporal lobe area are at high risk of rapid deterioration especially within the first three days after injury.
–An epidural hematoma greater than 30 cm squared should be evacuated regardless of GCS score
–An epidural hematoma less than 30 cm squared, midline shift less than 5mm, and thickness less than 15 mm in a patient without neurological deficit can usually be considered for nonsurgical treatment if clearly clinically stable
–Acute epidural hematoma is best treated by craniotomy rather then burr holes. Tacking up of the dura to prevent rebleeding should be done.
Acute Subdural Hematoma
–An acute subdural hematoma with a thickness greater than 10 mm or midline shift greater than 5 mm should be evacuated regardless of GCS score
–Patients who have a large parenchymal contusion and acute subdural less than 10mm with an admission GCS< 9 and then subsequent deterioration may be a candidate for surgery.
–In severe cases of brain swelling. Bone flap removal and duraplasty may be necessary.
Surgery for Traumatic Intraparenchymal Lesions
–Surgery for resection of intraparenchymal lesions is not within the normal procedure guidelines for general surgery.
–Patients with focal intraparenchymal lesions who present with a GCS of 8 will be initially placed on medical management protocols.
–Patients with a GCS of 8 who deteriorate despite medical management will be discussed with the neurosurgical staff as regards to management
Chronic Subdural Hematoma
–A totally asymptomatic patient with evidence of a chronic subdural hematoma may be conservatively followed
–A symptomatic patient with chronic subdural hematoma should undergo timely operation
–The best outcome in chronic subdural hematoma was found in a prospective study utilizing the two burr hole technique with subdural drain placement. At Ayder an initial burr hole will placed frontally or parietally depending upon where the greatest thickness of the hematoma is found. If after irrigation of the subdural space the brain does not expand to the dura then a second burr hole will be placed. If the clot is gelatinous then the burr holes will be converted to a craniotomy. A pediatric feeding tube will always be place in the subdural space at least one centimeter beyond the proximal last side hole and exited through a separate stab wound.
–The subdural drain may be removed when the old blood drainage converts to CSF. The drain should be removed by the morning of the third day after surgery.
–After surgery while the subdural drain is in place the patient’s head should be kept flat to maximize brain re-expansion which will push out the remaining subdural hematoma
–If patient deteriorates following surgery after initial improvement or fails to improve then consideration for a repeat CT scan should be done.
Closed Depressed Skull Fracture
–Patients with a closed depressed fracture with a depression less than 1 cm and no neurological findings or associated hematoma requiring surgery are potential candidates for conservative treatment
–A closed depressed fracture with a depression 1 cm or greater (which is deeper then the inner table) and/or neurological deficit should under go timely surgical intervention.
–Patients with simple depressed fractures without dural tear or cerebral contusion require only routine pre-operative antibiotic prophylaxis and no anticonvulsant prophylaxis.
Open Depressed Skull Fracture
–Patients with an open depressed fracture greater than the depth of the calvarium should undergo surgery.
–Operation should be done within the first 48 hours after injury to reduce the risk of infection.
–The bone flap or fragments should be cleaned with betadiene and saline thoroughly before replacement
–A water tight closure of the dura should be attempted..
–Debridement of nonviable and contaminated brain should be done.
–A 24 hour course of intravenous Ceftriaxzone and Metronidazole should be given for cases where there is only minimal contamination and the dura is intact. Patients will then receive a 7 day oral course of Amoxicillin and Clavulanate (Augmentin) 500 mg every 8 hours for adults.
–An 7 day course of intravenous Ceftriaxzone and Metronidazole should be given for cases where there is extradual purulence, gross contamination or penetration of the brain especially if surgery was delayed more than 48 hours after injury.followed by a one week course of Augmentin orally.
–Post traumatic cerebritis or abscess requires 6 week course of intravenous antibiotics.
–Anticonvulsant prophlaxis should be given to all patients with dural laceration and open brain injury.
The academic new year at Mekelle University for residents (doctors who have graduated from medical school and now will undertake several years of specialty training) is just a few weeks away. They will transform from the theoretical and observing from the sideline to actually being involved in medical care to improve the quality and longevity of their patients. A part of the new experience will be their discovery that there is a limit of resources even in the richest countries and of course more severe in the developing countries. This same thing is happening not just in Mekelle, not just in Ethiopia, but around the world in all the teaching hospitals.
Although we like to pretend otherwise there is no escaping the inevitable fact that we are mortal and will at some point suffer significant illness followed by death. An Ethiopian diaspora calculated based upon the year 2000 that the per capita lifetime medical expenses where $316,000 in the state of Michigan (USA). Most of the cost occurs in the first year of life and after age 50. Women were more than men because they live longer. About one third occurs in middle age and about one half in the senior year of life.
It is hard to put a measure on the value of human life.
When discussions occurred about the use of dialysis as to whether should be payed for by government, analysts determined that spending $50,000 to give an additional year of quality life was worthwhile. This same measure was applied by several governments world wide. The actuarial value of a human life in developed countries is put somewhere between $ 500,000 and ten million dollars by actuarial experts. It is much less in developing countries where the economic output of an individual is much lower often less than a few hundred dollars a year.
The most recent budget for healthcare in Ethiopia was 1.4 billion dollar equivalents which cames out to about $14 per person for the approximately 100 million Ethiopian population. If you count out of pocket expenses it increases to about $24 per capita. This is of course much less than than the $4000-$5000 you see in European countries and the almost $10,000 in the United States. Yet even in these rich countries there are cries that funding is insufficient.
This means that physicians and the policy makers whom they advise have to learn to do more with less. They have to spend resources where they will have most impact. How are these decisions made? Medical ethicists talk about years of productive life as a reasonable way to compare, for example, spending money to help newborns versus the elderly. But not all cultures would agree with this concept totally. There is often a belief that older citizens should be rewarded for their service to society. Note the creation of Medicare and Social Security and its equivalents in the United States and many other developed countries.
Good medical care even in this age of limits is possible. It requires a sound knowledge of likely outcomes, compassion, and realistic communications with the patients and the community at large in both developing and developed countries. The inevitable consequences of our mortality and economic reality of limits leaves no room for anything other than truthful sincerity.
Given the already highest incidence of neural tube defects measured globally present in Ethiopia it would seem exceedingly urgent to immediately call for the cessation of use of Valproic acid, which has been shown to cause neural tube defects, in women of child bearing age in Ethiopia except for special circumstances.
History of Valproic Acid
Valproic acid was first produced in 1882. At that time its discoverer did not imagine that would be any therapeutic use because it was thought to have no pharmacological value. Then in the 1960s it was begun to be used in France and then in the late 1970s was approved for use in the United States as a primary drug for first epilepsy and then also for migraine headaches as well as mood disorders.
Over the next thirty years, however, concerns began to be raised about the potential relationship of the drug and birth defects. Both a joint European study and a separate French study showed that women of child bearing age taking appropriate therapeutic doses of 1000 mg a day or more had a high incidence of neural tube defects and other malformations up to seven times higher than the control population.
Valproic Acid Use in Ethiopia
The use of Valproic acid is relatively new in Ethiopia in just the last few years. A review of the treatment of epilepsy from Gondar University showed that 4.84 % of patients were using it. In addition it is being used to treat mood disorders and migraine headache to an unknown extent. The prescription of this medicine is relatively unrestricted and can be done by general practitioners and even non-physician health care providers. Unfortunately the official formulary for Ethiopia briefly mentions that pregnancy is a contraindication and suggests consideration for folic acid supplementation should be given to reduce the risks of birth defects. However a recent animal model study using chick embryos showed that supplemental folic acid for neural tube defects caused by valproic acid was not effective in prevention.
Neural Tube Defects in Ethiopia
Our research at Mekelle University looking at the incidence of neural tube defects in the Tigray region of Northern Ethiopia suggested an over all incidence of at least 130 per 10,000 births but with some locals reporting close to 300 per 10,000 births. We know from studies done by the Ethiopian Institute of Public Health that 28% of women of children bearing age throughout Ethiopia have a significant folic acid deficiency which is likely the strongest contributing factor to the high incidence of neural tube defects
Recommendations for Valproic Acid Restriction in Ethiopia
1.Given the already highest incidence of neural tube defects measured globally present in Ethiopia it would seem exceedingly urgent to call for the immediate cessation of use of Valproic acid in women of child bearing age except for situations where no other drug can be used and the patient is receiving implantable or injectable forms of birth control.
2. Prescription of Valproic acid should only be done by physician sub-specialists in neurology, neurosurgery, or psychiatry and should require extensive counseling to the patient.
3.The formulary of Ethiopia should be modified and vigorously amended to warn of the risks. Although consideration for folic supplementation is appropriate it should be clearly stated that such supplementation may not be effective in preventing birth defects.
Traditionally surgery for hydrocephalus has been performed by neurosurgeons who undergo vigorous neuroscience basic training and supervised surgical experience of at least 5 years in length (longer in developed countries) after medical school. Recently there has been some discussion as to whether in African and other undeveloped countries general surgeons should be taught to perform ventriculoperitoneal shunts to treat hydrocephalus. The treatment of hydrocephalus should remain under the direction and in the hands of neurosurgeons.
Hydrocephalus as a medical condition has been recognized since the time of the ancient Greeks. The concept of surgery to treat hydrocephalus by diverting the flow of cerebrospinal fluid began in 1949, when Nulsen and Spitz implanted a shunt successfully into the caval vein with a ball valve. Between 1955 and 1960, four independent groups invented distal slit, proximal slit, and diaphragm valves almost simultaneously.
An estimated 750,000 people have hydrocephalus, and 160,000 ventricular peritoneal shunts are implanted each year worldwide almost always by neurosurgeons. About 56,600 children and adolescents younger than age 18 years have a shunt in place.
The incidence of hydrocephalus in Africa is estimated to be 145 per 100,000 which is three times higher than in the developed world. Thousands of these children will need surgical intervention, either ventricular peritoneal shunt or the newer, but still not clearly accepted as superior, endoscopic procedures.
A survey conducted among African neurosurgeons in 1998 showed that there were 500 neurosurgeons in Africa; that is, one neurosurgeon for 1,350,000 inhabitants, and 70,000 km2. That number is significantly increased now but the exact current number is unknown. Worldwide the average is 1 neurosurgeon per 230,000 but in Africa it can be as low 1 per 9 million people. It is believed there are 700 neurosurgeons currently or about 1 per 1,238,000 people which is an improvement but still not nearly enough. Ethiopia currently has about 30 practicing neurosurgeons and will soon be graduating about 30 newly trained neurosurgeons per year. This means Ethiopia will need about 450 functioning neurosurgeons taking into account expected population growth.
Although the training of neurosurgeons in performing ventriculoperitoneal shunts has become somewhat standardized via the World Federation of Neurosurgical Societies as well as international neurosurgical groups, the training of general surgeons to do this procedure has not been rigorously studied. There are very few publications about the results of general surgeons performing ventriculoperitoneal shunts but an a study from Kenya done in 2010 showed a significantly high complication rate of 65% with an infection rate of 9.1% and shunt malfunction rate of 11.1%. This was much different than reported by Dr. Warf , an American trained neurosurgeon who created a specialized center in Uganda, with a malfunction rate of 4%.
More recently endoscopic procedure to open the third ventricle to the cistern and coagulate the choroid plexus are gaining ground but not totally proven yet. These procedures clearly require specialized training and knowledge of anatomy of the caliber of a neurosurgeon and not a general surgeon.
The real issue was not really the shortage of surgeons but the bottleneck was lack of hospitals, operating rooms, and clinics. Additionally transportation to get healthcare is a real issue. Now Ethiopia has seen the light and has three training programs for neurosurgery in Ethiopia and are graduating about 30 per year. Again the problem is we have more surgeons than facilities to operate in.
African governments will see the idea of adding shunt placement to general surgery as an easy fix. In reality they are already overworked. I have taught medical students and general surgery residents. Many people think ventriculoperitoneal shunts are the easiest procedure but I always tell my neurosurgery residents and fellows it is not. Decisions about when to shunt, is the shunt working, is it infected? require experience and training. Academic following of outcomes, techniques, epidemiology requires an academic neurosurgery program take the lead.
Unfortunately there is no shortcut to capacity building. We are now training neurosurgeons for other African countries as well as Ethiopia. Eventually we will need more than 450 which will take time.
Finally I would say that our approach to hydrocephalus is changing rapidly. For us and the Uganda group we are consistently reducing the number of shunts we are doing each year. Whereas in the past we did nearly two hundred it is now going to be less than 100 even though we cover 20 million plus population with the highest myelomeningocoel rate in the world. We now recognize that many neural tube defect newborns have low grade infections which require antibiotics sometimes over 21 days until the csf is clear. Many times their hydrocephalus stabilizes after a few fontanelle taps. Although the post infectious group is rising ( we are in the infamous meningitis belt of Africa) similar we have avoided shunting by similar close follow-up. Our shunt infection rate is currently 3% because we identify these chronic low grade infections. I shutter to think what would happen if general surgeons with little experience are let loose upon this situation.
At Ayder Comprehensive Specialized Hospital, the university medical center for Mekelle University in Ethiopia, our experience with finely controlled hypotension during brain surgery for both adults and children has reduced the need for blood transfusion by half.
In many underdeveloped African countries the surgical treatment of brain tumors is often very late in the course of the disease due to delay in the patient seeking treatment, having a diagnostic study to find the tumor, and being scheduled for surgery as many university centers have long waiting lists. Such is the situation we are in Ethiopia. These large brain tumors, often 10 centimeters or more in diameter, can require massive transfusion during the surgery to remove or reduce them.
The Department of Neurosurgery in the School of Medicine at Mekelle University in a close partnership with our Department of Anesthesia has been working on creating sustainable safe controlled hypotension techniques to reduce our blood loss during brain tumor surgery in adults and children at Ayder Comprehensive Specialized Hospital. Thanks to the donation of a high quality intravenous perfuser by a diaspora American anesthesiologist and the cooperation of the university to gain stocks of Isoflurane inhalation agent and Propofol intravenous agent as well as in house training together we have significantly reduced blood loss leading to much less transfusion during brain surgery. End tidal CO2 is kept at 4.5 to 5% and mean arterial blood pressure maintained at 65-70 mm/Hg.
A joint study by the Departments of Neurosurgery and Nutrition (School of Public Health) of Mekelle University and the Department of Epidemiology of Emory University has concluded that thousands of newborn deaths and lifelong disability from neural tube defects could be prevented by fortifying food and possibly salt with folic acid to significantly reduce the epidemic currently occurring in Ethiopia.
Ethiopia is now at a point where non-communicable disease is overtaking the classic major infectious and malnutrition disorders which dominated the major morbidity and mortality for the country. Now more than ever with scant resources and unique cultural situations there is a need for effective clinically related medical research at the top universities in Ethiopia. Effective clinically related medical research in Ethiopia requires that academic medical centers begin to train physician-scientists.
Unfortunately the model of how to do medical research and by whom it should be directed and/or overseen is outdated. Because medical schools lagged behind the development of fields like Public Health and Nursing these entities dominated the university structure. At the beginning there were no specialists and very physicians who were so overworked they really had no time for training in methods of research let alone doing it.
Today over 50% of the needs of Ethiopian doctors require specialist training. Additionally the experiments such as occurred in British National Health Service of relying on mostly non-physician scientists to direct and oversee medical research backfired. In the current system almost no funds are directed to physician directed medical research yet Ethiopia desperately needs physician-scientists to lead the way into dealing the health care needs of a growing population of over 100 million people.
We are currently advocating changing this system at Mekelle University. Similar changes are already occurring at St. Pauls Millenium and Addis Ababa University in Addis Ababa, Ethiopia.
The Alliance for Academic Internal Medicine has published these recommendations for training physician-scientists which I think should be strongly considered for adoption wholly or least substantially in Ethiopian university training centers.
Summary of Best Practice Recommendations for Physician-Scientist (The American Journal of Medicine, Vol 131, No 5, May 2018) Physician-Scientist Training Programs (PSTPs) Curriculum and Infrastructure
A. Providing combined residency and subspecialty fellowship training is an attractive feature.
B. PSTPs should include training in study design, biostatistics, team science, ethics, scientific regulatory requirements,
institutional review board application, grant writing, time management, leadership, work/life balance, and mentor/mentee
C. Directors of PSTPs would benefit from organizing a formal alliance and meeting regularly. Recruitment and Selection of Trainees
A. Candidates for PSTPs most likely to translate their training into successful careers as well-established physician-scientists
are those who have significant research experience and can demonstrate a balanced commitment to both science and
B. PSTPs should make increasing diversity among its trainees a stated goal, with active efforts to recruit qualified women and
members of underrepresented minority populations.
C. Initiatives to recruit qualified international medical graduates as trainees should be increased and additional sources of
funding for international medical graduates trainees should be pursued. Mentorship Practices
A. Mentoring teams are essential for PSTP trainees and should be carefully crafted.
B. Mentors need to be formally trained in mentoring, and they need to be recognized for their contributions.
4. Funding of PSTPs and Their Trainees
A. The success of PSTPs and their trainees is highly dependent on strong institutional support.
B. The success of PSTPs and their trainees is also highly dependent on adequate levels of external funding including the
successful receipt of individual career development awards. Tracking Success of PSTPs and Their Graduates
A. Success factors of PSTPs and their graduates should be tracked.
B. Tracked data should be coordinated with other PSTPs and shared in a national data base.
6. Sustaining PSTPs and Employing Continuous Improvement Practices
A. Sustainability is contingent on institutional support and an adequate census of qualified applicants.
B. Sustainability is also impacted by the percentage of trainees who successfully complete their training.
Neurosurgery began to function as a unit in September 2015 with addition of a full time senior neurosurgeon. The Department of Neurosurgery officially separated from being a unit in the Department of Surgery in January of 2018 to become its own department in the School of Medicine. The Department will perform more than 1000 operations per year, train neurosurgical residents, teach medical students, carry out research and community service for Tigray and Ethiopia.
Academic Activities The Neurosurgery Training Program
The neurosurgery training program which began in January 2018 consists of either a five year residency program for general practitioners or a three year fellowship for general surgeons was initiated. The training program is recognized by the Ethiopian Ministry of Health and participates in the Ethiopian National Matching Program for general practitioners to join post graduate medical training programs. Ayder Comprehensive Specialized Hospital and the Neurosurgery training program are certified to give training programs by the College of Surgery East, Central, and South Africa and their member countries. The program is now beginning its second year. Currently there are a total of 2 fellows and 13 residents in the program.
Besides teaching neurosurgery residents the Department provides rotations and didactic session for General Surgery, Ear Nose and Throat, Oral Maxillofacial, and Orthopedic residency trainees. The Neurosurgery department participates in the teaching of C1, C2, and interns under the General Surgery course offered by the School of Medicine.
Current and Future Enrollment Plans for the Neurosurgery Department Training Program Estimates of Ethiopia’s future need for neurosurgeons based upon World Health Organization estimates for specialists assume there is a need for one neurosurgeon for every 250,000 population. Ethiopia will need in excess of 400 practicing neurosurgeons for its rapidly growing population reaching over 100 million. Currently there are less than twenty practicing neurosurgeons most of whom are in Addis Ababa. Currently there are three programs ( Addis Ababa University, St. Paul Millenium, and Mekelle University) which are taking in about 21 new trainees per year. Recently about 40% of graduates have left the country to practice in other countries such as Malawi, Uganda, and Somali-land. No new training programs are expected in the new future.
The Neurosurgery Department has agreed to take four PGY1 trainees in the Fall of 2019 to be assigned by the Ministry of Health to be trained at Ayder CSH. We will continue to take four PGY1 each following year.
The Neurosurgery Department plans to expand its clinical services, training, and teaching as the new cancer center, Quiha Trauma Center, and Pediatric Neurosurgery Center of Excellence are established in the future. When these development occur we will increase our resident intake to potentially 6 to 8 per year instead of the 4 per year currently. (This development is further discussed in staffing report below)
Staff The Neurosurgical Department has three total active staff and five recruited staff in training.
Current and Future Staffing Plans
Our perceived need for training requirements, teaching, research, and clinical care at Ayder Comprehensive Specialized Hospital is 8 full time faculty. At the current time the 300 bed cancer center is under construction with planned opening sometime in the next two years.
Additionally we are having discussions with the Tigray Regional Health Bureau about
1. Providing neurosurgical services and extending the training program to the H.E.W.O. Hospital in Quiha which would would function as a Pediatric Neurosurgery Center of Excellence. Mekelle University, Tigray Regional Health Bureau, and the Reach Another Foundation (USA and Netherlands NGO) have signed a Memorandum of Understanding to develop such a center.
2. Providing neurosurgical services and extending the training program at the Quiha Hospital in Quiha. Currently there is a 100 bed trauma building under construction there which will possibly be finished in the Fall of 2019.
Once the cancer center construction is completed and assuming neurosurgical services and training are extended to the cancer center, Quiha Hospital, and the H.E.W.O hospital then our full staffing requirements for senior staff would increase to 12 (twelve). The Tigray Regional Health Bureau has one employee in training (Dr. Assefa) which is assigned to Mekelle upon his finishing in two years. We have discussed sharing this individual jointly with the Tigray Regional Health Bureau.
Professor Tony has consulted with the Department of Anatomy in developing a Ph.D. Program in Neuroanatomy with experience in Neuroscience which has been approved by the University but is awaiting final approval by the Ministry of Science and Higher Education. He will be co-appointed in the Basic Sciences and serve as a graduate sponsor and advisor for the Ph.D. Program.
Research Professor Tony Magana is the founding member of the multidisciplinary neural tube defects research team consisting also of members from the Departments of Anatomy (Embryology, Teratology), Microbiology Pediatrics, Surgery, Obstetrics/Gynecology, and School of Public Health ( Department of Nutrition). Four peer reviewed publications have been accepted in major internationally recognized journals. Professor Tony and other members of the team served as advisors to the Ethiopian Public Health Institute and the Ministries of Health and Maternal/Child Welfare for recommendations in developing a national policy to deal with neural tube defects. This recommendation was formalized in June 2019.
1. Berihu BA, Welderufael AL, Berhe Y, Magana T, Mulugeta A, Asfaw S. High burden of neural tube defects in Tigray, Northern Ethiopia: Hospital-based study. PloS one. 2018 Nov 14;13(11):e0206212.
2. Berihu BA, Welderufael AL, Berhe Y, Magana T, Mulugeta A, Asfaw S, Gebreselassie K. Maternal risk factors associated with neural tube defects in Tigray regional state of Ethiopia. Brain and Development. 2019 Jan 1;41(1):11-8.
3. Welderufael AL, Berihu BA, Berhe Y, Magana T, Asfaw S, Gebreselassie K, Belay E, Kebede H, Mulugeta A. Nutritional status among women whose pregnancy outcome was afflicted with neural tube defects in Tigray region of Ethiopia. Brain and Development. 2019 May 1;41(5):406-12
4. Dixon M, Kancherla V, Magana T, Mulugeta A, Oakley GP. High Potential for Reducing Folic Acid-Preventable Spina Bifida and Anencephaly, and Related Stillbirth and Child Mortality, in Ethiopia. Ethiopia (May 3, 2019). 2019 May 3.
Clinical Activities The Department provides care including consultation and surgery for adult and pediatric patients with disorders of the brain, spine, and peripheral nerves at Ayder Comprehensive Specialized Hospital.
Outpatient at Ayder CSH
The source of patients coming to Ayder CSH includes not only Tigray but also in increasing numbers Eritrea, Afar, and the Amhara regions. Ayder CSH is most advanced hospital outside of Addis Ababa in Ethiopia. Several times a month we even receive referral from Addis Ababa for some unique surgical services we offer including:
1. endoscopic pituitary tumor surgery
2. microsurgical nerve transplant
3. surgery for cranial-facial disorders
4. surgery for cerebrovascular disorders (aneurysm)
5. complicated pediatric brain tumors
Outpatients are seen in a once a who week referral clinic (Thursday) and in the emergency area twenty fours a day seven days a week. Approximately 7 (weekdays) to 10 (weekends) patients are evaluated in the emergency area every 24 hours. The number of outpatients seen in the referral clinic has grown from about 50 in 2016 to 90 per clinic day currently. Many patients wait several months for available appointments. The old clinic facility had most of the clinic day only two available stations as it was shared with general surgery clinic the same day. A new clinic facility is being set up which will be shared with Orthopedics on alternating days wherein the Thursday referral clinic will have four stations with computers instead of only two stations and an additional half day morning clinic will be added on Tuesdays. A small daily clinic attended by a junior resident is being considered when increased manpower in the neurosurgery department comes into being.
Outpatient Clinic and Emergency Room Average Daily or Weekly New Consults
Weekly Neurosurgery Referral Clinic
100 per week/400 per month/4800 per year
Emergency Room Adult
6 per day/42 per week/168 per month/2016 per year
Emergency Room Pediatrics
3 per day/21 per week/84 per month/1008 per year
Inpatient Care at Ayder CSH Average Daily Neurosurgical Census Data for Neurosurgery at Ayder CSH
Total inpatients visited daily/monthly/yearly
28 to 34 daily/960monthly /11,520 yearly
Three operating room days during the working week are alloted to neurosurgery for elective surgery. Emergency care is given 24 hours a day dependent on the availability of beds in the hospital, availabile operating room, anesthestists, and nursing staff.
Neurosurgical Operations at Ayder CSH
9 per week /36 per month/432 per year
2.5 per day/17.5 per week/70 per month/840 per year
Collaboration and Donation Emory University, Atlanta, Georgia USA
Child Help-International (Belgium) and the International Federation for Hydrocephalus and Spina Bifida (Belgium)
Reach Another Foundation (USA and Netherlands)
Hearts Helping Hands(USA)
Yves Meyers, Aesculap Corporation, and Dallas Memorial Hospital(USA)Quest Medical Supply(USA)
Quiha Hospital (Tigray Regional Health Bureau)
Over the past year in response to the Mekelle University Multidisciplinary Research team publications on neural tube defects in Tigray we have been interacting with the Ministry of Health, Maternal and Child, and the Ethiopian Public Health Institute. Two months ago Dr. Afework Mulugeta and myself as well as invited international experts gave a scientific advisory of this problem to the EPHI.
Yesterday a brief was given by the EPHI which was mostly based upon our research and recommendation as well as their review of available evidence.
Officially now the Ethiopian government recognizes “that there is an alarmingly high rate of neural tube defects and folate acid deficiency in Ethiopia”. The following recommendations were made to the higher ministry officials for approval
1. Periconceptional oral folate supplementation for all women of reproductive age as an immediate solution. Low cost imported folic acid is available for the public to purchase.
2. Making the first visit for pregnancy earlier instead of the current 16 weeks
3. Promoting the consumption of folic-rich foods.
4.Implementing mandatory wheat-flour food fortification.
5.Considering salt fortification with folic acid after doing a pilot study in Tigray
6.Establishing a surveillance system for NTDs throughout Ethiopia
7. Awareness creation for all recommended interventions strategies for the prevention of NTDs
Further studies will be done on community basis and on salt
Monitoring of food fortification measures to evaluate effectiveness