152 CMAAO CORONA FACTS and MYTH BUSTER Covid in Children, Neurology

152 CMAAO CORONA FACTS and MYTH BUSTER Covid in Children, Neurology

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

9743: Minutes of Virtual Meeting of CMAAO NMAs on “Covid in children & Covid and neurology”

11^th July, 2020, Saturday, 9.30am-10.30am

Participants, Member NMAs

Dr KK Aggarwal, President CMAAO

Dr Yeh Woei Chong, Singapore Chair CMAAO

Prof Ashraf Nizami, Pakistan First Vice President CMAAO

Dr N Gnanabaskaran, President Malaysian Medical Association

Dr Marthanda Pillai, Member World Medical Council

Dr Alvin Yee-Shing Chan, Hong Kong, Treasurer CMAAO

Dr Koh Kar Chai, Malaysia Co Chair CMAAO

Dr Marie Uzawa Urabe, Japan Medical Association

Dr Qaisar Sajjad, Pakistan Medical Association, Secretary

Dr Prakash Budhathoky, Nepal Medical Association

Invitees

Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia

Dr Sanchita Sharma, Editor IJCP Group

Prof Ashraf Nizami and Dr Alvin Yee-Shing Chan spoke on Covid in children and Covid and neurology, respectively. Here are key points from each presentation.

Covid-19 in children and Pakistan

Prof Ashraf Nizami

First Vice President CMAAO

Immediate Past President PMA Center
President PMA Lahore

In his presentation, Prof Ashraf Nizami spoke on Covid-19 in children and also highlighted the role of government and particularly the Pakistan Medical Association (PMA) in dealing with Covid-19 in Pakistan. The first case was reported in Pakistan on 6^th February.

• There was a general perception that children are not affected by this pandemic. But the fact is that all children of all ages in all countries are affected. This is a universal crisis and will have lifelong impact for some children as it is not just a health issue. It is also social and psychological issue.

• Clinical symptoms in children include abdominal pain, diarrhea and vomiting, red rash, cracked lips, red eyes, high fever, swollen glands on neck and swollen hands and feet.

• As per data on July 1, about 7.28% of the total reported cases in Pakistan are in people below 19 years of age. The mortality is 0.46% (16 out of 3501 under 15 years). Three suspected cases of Kawasaki disease have been reported in Lahore; also from Karachi, Rawalpindi and Islamabad.

• Covid has an impact on social growth. About 30% of industry is affected. Education is disturbed and only about 30% of children in Pakistan have access to technology in education (online). Healthcare services have been affected. Covid has also affected the physical and mental growth of children.

• The pandemic has led to anxiety and depression not only in children but also the parents. Incidence of domestic violence against women has increased due to lockdown, which has an impact on children and the family. Exploitation and child abuse have happened.

• Covid-19 has compromised access to health services due to lockdown; the basic health services are delayed due to SOPs in place. Polio vaccination has been affected; besides Pakistan and Afghanistan, recent outbreaks have been reported in Africa, East Asia and the Pacific.

• The government is creating awareness about the disease; special institution have been designated for children. Special counters have been created in hospitals.

• According to UNICEF, adequate water, sanitation and hygiene services for households, schools and healthcare facilities are essential to prevent spread of infectious diseases including Covid-19; 3 billion homes do not have soap and water; 900 million children do not have soap and water at schools.

• PMA is an active participant in Covid-19 activities. It was the first organization in Pakistan which spoke about Covid-19 and created awareness and raised an alarm about the outbreak. It also looks after coordination among doctors, government, social activities and people. A scientific meeting was organized for family physicians, who are considered as front liners. PMA is also developing guidelines with information derived from WHO, CMAAO, London School of Economics etc.

• PMA is working on telemedicine facilities, analysis of government policies, plans and actions. It is playing an active role in advocacy and implementation of WHO recommendations as per local needs as well as international experiences.

• PMA is pressing upon the government that curative services should not be compromised, to start immunization services with all SOPs; it is critical of the government’s decision to reopen schools. Psychology and psychiatric teleconsultations are being planned.

Covid and Neurology

Dr Alvin Yee-Shing Chan

Treasurer CMAAO

Vice Chairman, HKMA Charitable Foundation

• About 36.4 % of Covid patients from Wuhan China had neurological involvement; manifestations were more in cases of severe infection.

• Acute cerebrovascular diseases occurred in 5.7% of those severe cases vs 0.08% of milder cases.

• 14% of severe cases had impaired consciousness vs 2.4% of mild cases.

• Musculoskeletal injury occurred in 19.3% of severe cases vs 4.8% of mild cases.

• Neurological signs and symptoms are much higher in patients in intensive care: mental confusion and agitation (69%), diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, bilateral extensor plantar reflexes (67%).

• 33% of discharged patients (33%) had dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command

• MRI brain, in most of the patients, will show leptomeningeal enhancement, bilateral frontotemporal hypoperfusion, ischemic stroke; encephalopathic pattern on EEG.

• Clinically, these patients may have milder symptoms (hyperosmia, anosmia, headache, weakness, altered consciousness); patients with more severe infection have encephalitis with demyelination, neuropathy, and stroke.

• Invasion of the medullary cardiorespiratory center by the SARS CoV-2 virus may cause refractory respiratory failure in ICU patients.

• The route of entry is mostly through olfactory bulbs – olfactory tracts in the brain.

• Human coronaviruses have neuroinvasive capability. Misdirected host immune responses can damage the CNS, which is associated with autoimmunity in the susceptible persons, resulting in virus induced neuro-immunopathology. The virus replication directly damages the CNS.  ACE2 receptors occur in olfactory epithelium 70 times more than in tracheal or nasal epithelium. This is why anosmia occurs so frequently in this disease.

• The ACE2 receptor expression differs in neurons and glial cells and so immunopathology differs in different persons.

• Since ACE2 receptors are present in brain cells, the BBB presents no problem to the new corona virus. The virus has been detected in brain samples on autopsies and offers an explanation about the neurological sequelae even when the patients survive.

• Possible mechanism of direct neuronal damage: The trans-neuronal retrograde machinery is a possible route of neuronal invasion. The virus first infects peripheral neurons to invade the CNS via the axonal retrograde transport. It infects another neuron via synapses. The virus is released by exocytosis in the presynaptic terminal. It then binds to ACE2 receptor on the postsynaptic neuron. It gains entry into the neuroplasm via the receptor-mediated endocytosis. It causes cell death via apoptosis.

• Covid-19 induces anti-cardiolipin antibodies → endothelialitis → thrombosis (venous and arterial) → stroke, cerebrovascular accidents.

• The direct attack on neurons will cause milder cases, but if there is massive invasion of key neuronal cells, this may cause dysexecutive function. The vasculitis and endothelitis is instrumental in severe cases → stroke, and cell death due to ischemia.

• Hong Kong has very few pediatric patients and they have mild infection. There is resurgence in community spread with more than 40 cases with no obvious source. 7500 tests in a day, which is inadequate. No medical health staff has been infected through hospital or clinic. The silent cases in community are a cause of concern.

Acute presentation

Dr KK Aggarwal

President CMAAO

Look for the following points in every patient who presents with onset of illness less than
3 months. Classifying patients accordingly makes it easier to manage them.

• Is the clinical presentation of Covid is due to inflammation? There will be signs of inflammation like IL-6, ESR, CRP, ferritin → Give anti-inflammatory drugs; steroids are the most potent anti-inflammatory drugs
• Can this be because of hypercoagulable state? e.g. thrombotic stroke/MI/appendicitis/gangrene/happy hypoxia (microclot formation in lung vessels): Do d-dimer; high d-dimers mean hypercoagulable state  
• Is there any immunological reaction (immediate or delayed) - humoral? Vasculitis, look for rash, CRP is normal, high platelets;
• Is there cellular immunological response? Cytokine crisis
• Except for hypercoagulable state, all will respond to steroids. So, combination of LMWH and steroids is standard treatment.
• Some patients may have simple viral response and illness will resolve spontaneously in 2-3 days; some will show a bacterial response with slightly high polymorphs – typhoid test may be falsely positive in such patients; some patients may have low CD4 count indicating HIV-like activity.

 

133 CMAAO CORONA FACTS and MYTH BUSTER Neurology

133 CMAAO CORONA FACTS and MYTH BUSTER Neurology

Dr K K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

955: Update on Covid-19: IMA-CMAAO Webinar on “Neurological complications in Covid-19”

6th June, 2020, 4-5pm

Participants

Dr KK Aggarwal, President CMAAO

Dr RV Asokan, Hony Secretary General IMA

Dr Ramesh K Datta, Hony Finance Secretary IMA

Dr Sanchita Sharma

Faculty

Dr Jyoti Sehgal

Senior Consultant Neurologist

Medanta Medicity, Gurgaon

Key points from the discussion

• These patients are seen in triage, OPDs or as referrals from ICU from other departments.
• Neurological manifestations in Covid-19 patients may be of the central nervous system or peripheral nervous system.
• In CNS, the symptoms may be mild and nonspecific – headache, vertigo, fatigue, uneasy feeling or not feeling good.
• Patients with altered sensorium (irritability, confusional state, seizure-like), disorientation and encephalopathy are critical patients and admitted to ICU. These patients do not have symptoms of cough, fever, respiratory distress.
• There are no imaging findings on CT scan, their MRI may be normal; mildly high protein; treatment is symptomatic.
• Many patients come as stroke (hemiparesis, facial involvement, deficit which is measurable) in casualty; they are managed as per management of acute stroke and when hospitalized are subjected to mandatory Covid test. Ischemic stroke is more common.
• In many patients, the first report may be negative, but the subsequent repeat test turns out to be positive.
• Patients can also present with epilepsy or seizure-like presentation.
• There are patients who have comorbid neurological conditions like Alzheimer’s, Parkinson’s, multiple sclerosis, motor neuron disease, who have altered sensorium or have stopped doing their daily activities for the last few days.
• Patients also have peripheral nervous presentation, which can be anosmia, different sensation of smell, Bell’s palsy (infranuclear).
• Patients in ICU, patients on ventilators present with critical illness polyneuropathy or critical illness myopathy.
• Patients who are on immunosuppressants like MS, myasthenia are more prone to disease relapses even if earlier were stable on low dose medication.
• Treatment is supportive; protection of staff and HCW; dedicated corridors and floors; dedicated CT scan machine. Once the report is negative, the family is also counseled and shifted to non-Covid ward.
• High d-dimer may be indicative of Covid stroke.
• LMWH is reserved for bed ridden patients (hemiplegia, paraplegia, transverse myelitis, GBS) as DVT prophylaxis.
• Neurological care in Covid: We have become more historical – good clinical and visual history is helping to make a clinical diagnosis as there is fear of examination; fewer investigations and more of clinical judgment; hospitalization is discouraged; relying on families and relatives as caregivers

AAN-AHA updated pediatric migraine guidelines: Treat as soon as the child becomes aware of an impending migraine attack

Dr KK Aggarwal

The American Academy of Neurology (AAN) and the American Headache Society (AHS) have published updated recommendations for preventing and treating migraine in children and adolescents

The guidelines focused on two areas: one, acute treatments to reduce pain and other symptoms that accompany the headache and secondly, treatments to prevent migraine attacks and reduce the associated morbidity. Some key recommendations are:

·         Migraine should be treated as soon as the child or the adolescent becomes aware of an attack starting. Treatment is most effective when given early in the attack.

·         A detailed history and physical examination, including a neurological examination that may need to be conducted by a neurologist or headache medicine specialist is recommended.

·         Educate the patients and their parents about migraine and factors that trigger the episode such as lack of physical activity, being overweight, excessive caffeine intake, poor sleep habits and dehydration

·         Mood disorders (depression and anxiety) often co-occur with migraine. Adopting a healthy lifestyle – healthy eating, physical activity, adequate hydration and adequate sleep will help in managing them.

·         The risks and benefits of preventive medication and appropriate acute treatment should be discussed with the patients.

·         Ibuprofen, triptans and combination sumatriptan/naproxen may be used to relieve pain.

The guidelines are published in the August 14, 2019, online issue of the journal Neurology.

(Source: American Academy of Neurology)

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

New drug: Solriamfetol improves excessive daytime sleepiness

A new drug, solriamfetol (75, 150, or 300 mg) improved wakefulness on the Maintenance of Wakefulness Test (MWT) and reduced excessive sleepiness on the Epworth Sleepiness Scale (ESS) over a 12-week treatment period when compared with placebo in patients with narcolepsy published in the March 2019 issue of Annals of Neurology.

These improvements were observed in the first week of the study itself and were maintained for the 12 weeks of the study indicating that there was no apparent tolerance to the drug over the study period.

Solriamfetol showed dose‐dependent efficacy that was significantly superior to placebo on both coprimary endpoints at the 150 and 300 mg doses. Solriamfetol 75 mg dose showed greater improvement than placebo on the ESS but not on the MWT.

What is it? Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects.

Side effects: Headache, nausea, loss of appetite, nasopharyngitis, dry mouth and anxiety

Regulatory status: Solriamfetol has been FDA approved to treat excessive daytime sleepiness in adults with narcolepsy or obstructive sleep apnea (OSA). Approved doses are 75 mg and 150 mg for patients with narcolepsy and doses of 37.5 mg, 75 mg and 150 mg for patients with OSA. It is to be administered once-daily.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Four trials published in 2018 that may shape neurology practice

• A new treatment option for brain metastases: The usual survival period after brain metastases is 2-4 months. Brain metastasis generally means palliative care. In a study published online August 2018 in the New England Journal of Medicine (N Engl J Med. 2018;379:722-730), nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had asymptomatic untreated brain metastases. Benefit in intracranial growth of metastases was seen in 57% of patients, 64% of patients did not show any progression of the disease, and the 6-month survival was 80%.

• Gut linked to pathophysiology of Parkinson’s disease: JAMA Neurology provided indirect evidence for role of systemic inflammation in the pathogenesis of Parkinson disease and inflammatory bowel disease in a retrospective cohort study of 144,018 patients with IBD (JAMA Neurol. 2018;75:939-46). Patients with IBD had a 28% higher incidence of Parkinson’s disease. A marked reduction in the incidence of Parkinson’s disease was observed when IBD patients were treated with anti–tumor necrosis factor therapy.

• No beneficial effect of aspirin for prevention of adverse CV events in moderate risk patients: The multicenter ARRIVE study compared the use of aspirin with placebo in more than 12,000 patients with moderate risk of heart disease (10-year risk of coronary heart disease 10-20%) (Lancet. 2018;392:1036-46). No beneficial effects with regard to the primary efficacy endpoint (composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischemic attack) were seen with aspirin after a follow-up period of 60 months.  Gastrointestinal bleeding events (mild) occurred more often with aspirin. Use of aspirin in moderate-risk patients needs to be individualized.

• Major bleeding risks offset primary prevention benefits of aspirin use in patients with diabetes: Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease (19% risk reduction) in the ASCENT trial (N Engl J Med. 2018;379:1529-39). Major bleeding events occurred in 314 participants in the aspirin group vs 245 in the placebo group indicating a 30% increase in the risk of major bleeding. So, the absolute benefits were largely counterbalanced by the bleeding hazard. 

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Exercise has no upper age limit: Moving more in old age linked to sharper memory

Older adults who move more, either with daily exercise or even simple routine physical activity like housework, may preserve more of their memory and thinking skills, even if they have brain lesions or biomarkers linked to dementia, according to a study published in the January 16, 2019, online issue of Neurology.

The study examined 454 older adults; 191 had dementia and 263 did not. All participants were given physical exams and thinking and memory tests every year for 20 years. Participants agreed to donate their brains for research upon death. The average age at death was 91. The brain tissue was examined after death for lesions and biomarkers of dementia and Alzheimer’s disease.

The study found that people who had better motor skills had better thinking and memory skills compared to those who did not move much at all. For every increase in physical activity by one standard deviation (SD), participants were 31% less likely to develop dementia. For every increase in motor ability by 1 SD, participants were 55% less likely to develop dementia. This association was consistent in people who had dementia and people who did not.

Today, most of us are less physically active even though the benefits of exercise on physical health as well as mental health are known to us all. Lack of initiative or lack of safe open spaces may have contributed to this scenario. A heavy work schedule is often a deterrent to physical activity for many of us.

Walking is the best form of exercise, which requires no investment, no special training. Walking in natural environments such as parks also reduces mental stress and fatigue and improve mood via the release of the ‘feel good’ endorphins. This proximity to nature also helps in the inward spiritual journey and shifts one from the sympathetic to parasympathetic mode manifested by lowering of blood pressure and pulse rate

(Source: American Academy of Neurology News Release, Jan. 16, 2019)

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA