Cannabis in Lennox-Gastaut Syndrome

One of the most painfully frustrating events in our practice of Neurology since the times of residency training has been the encounter with a refractory Epilepsy syndrome in a young patient. Not only we witness the suffering of the disgraced patients, who are losing intellectual capacity and the promise of a fruitful future, but also the terrible frustration of their parents and loved ones. Lenox-Gastaut syndrome is exactly that: an epilepsy variant that attacks young patients with “drop seizures” that are resilient to effective, long-term and non-toxic pharmacologic treatment.

A multi-center study that enrolled 171 patients form 24 clinical centers form the United States, the Netherlands and Poland studied the effects of the administration of Epidiolex, a CBD purified drug that does not contain any of the psychoactive components of Cannabis. Patients from the age of 2 and 55 years old who had failed to show improvement with at least two anti-epileptic drugs were eligible to participate; their mean age was 15 years old with six drug failures. They all had to have slow (less than 3 hertz) spike and wave patterns in their electroencephalogram, more than one type of seizure for at least six months and at least two drop seizures per week.

The participants were randomized to receive 20 mg/kg purified CBD oil daily (divided twice daily) or a matched placebo for 14 weeks. Their families actively participated as they helped them record the number of drop seizures and related events during the study. They were evaluated four times in their respective medical clinics and twice with a special telephone interview. The investigators studied the percentage change of drop seizures during the treatment period of 86 patients that received the drug and the 85 patients who were part of the placebo group. We must point out that all patients continued to receive their properly prescribed anti-epileptic treatment.

The median percent reduction in monthly drop seizures from baseline to the end of the study was 43.9% in the group receiving Epidiolex compared to 21.8% in the placebo group. Some patients receiving the drug even had a 50% reduction in seizures and three patients were even seizure-free during the whole study; nobody in the placebo group had a seizure-free period. There were some adverse events in both groups, including diarrhea, fatigue, fever and vomiting. Amongst the noted drug interactions, the patients taking Clobazam had an increase in its active metabolite, which led to higher sedation. Thirty-six treated patients that were also taking Valproic Acid had an increase in liver enzymes, which resolved after the CBD was stopped.

After the study was stopped in October 2015, an open-label extension study was started.

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Don’t leave me alone.

The excited executive

– “Doctor…Can’t go back home with so much excess energy—I need my escape valve.”

Sheila X. is a successful middle aged married executive in a large company that has succeeded at the top of the hierarchy and has remained there for years. At the end of her long workday she still feels “charged up” and needs an outlet. Three times per week she goes to the gym to stay in good shape, but it is not nearly enough. Once per week she has a clandestine date with a casual lover she finds in Tinder. Her very own escape valve.

The dating site named “Ashley Madison”, which supposedly specializes in discreet match-up of eager men and women for an affair, made an informal canvass of the most common professions of the unfaithful women and men that was posted in their website. They found that among women, the most unfaithful professions were the following:

  1. Business executives – 22%
  2. Information technology – 12%
  3. Technicians – 8%
  4. Education – 7%
  5. Medical personnel – 7%
  6. Marketing – Communications – 7%

Amongst men the most unfaithful professions (24%) were the ones that had very flexible schedules and timetables that allowed to camouflage a clandestine tryst.

Neurophysiological studies have shown that women confronted with stressful events secrete much more Oxytocin—the hormone of sexual desire—than men do, Moreover the presence of stress provokes the secretion of testosterone both in men and women as part of the ancestral biological defense mechanism of humans. The adrenal glands produce a small amount of that hormone in women that can increase if they are chronically exposed to various stressful situations; women are more sensitive to the testosterone’s effects, which include the sexual excitement.

Sexual desire in women is prodded by a complex assortment of visual, auditory and skin stimuli, coupled with a hormonal rush that reach the brain’s Hypothalamus. If the successful women executives are geared up for performing savagely like a professional boxer in the ringside, shouldn’t they also be allowed some time to relax after the fight?

What do you think? Please tell us.

Don’t leave me alone.

The “broken heart” syndrome

The massive influx of women in the workforce of modern nations has produced a widespread phenomenon of “double stress” in their lives as they usually must cope with the work and household requirements at the same time. Even though there has been a shift in the social customs as more men are becoming aware that they must share the household chores, including the rearing of children, there is still an asymmetry in the distribution of tasks. Women still work more. Much more.

Sadly, the recent statistics show that women are catching up with the morbidity and mortality due to cardiovascular diseases due to their newfound responsibilities. In the USA it is the leading cause of death and disability for women of all societal levels. Oftentimes the presentation of cardiovascular disease is atypical in women as they do not show up in the office with the traditional “angor pectoris”; they have persistent anxiety or asthenia or polymorphic pain syndromes in the extremities.

Early in their lives, the estrogens have a protective effect on their cardiovascular system as they promote the formation of HDL-cholesterol, which cleanses the vessels of atherosclerotic plaques. But as menopause approaches, they have less estrogens and the risk of cardiovascular anomalies increases significantly.

As women usually have a richer emotional dimension, there are more instances where they can suffer from an “emotional frustration” and bear consequences. In post-menopausal women an unusually strong emotional event can produce a particular syndrome called “Takotsubo’s cardiomyopathy”. The sudden release of a high amount of adrenalin produces transitory damages to the cardiac muscle with the corresponding clinical presentation mimicking a “heart attack” due to coronary artery disease; the laboratory values and electrocardiogram may be abnormal.

The angiography shows an increase dilatation of the left ventricle, which normally has a triangular shape; it becomes more elongated and rounded, resembling an inverted vase. The Japanese physicians that discovered this clinical syndrome in 1990 named it after the special utensil Japanese fishermen use to catch octopus. Once the acute episode subsides with proper medical therapy, the heart recovers completely and there are no permanent sequelae of a “broken heart” syndrome.

What do you think? Please tell us.

Don’t leave me alone.

Being fabulously single

-“Doctor…I’m finally having the time of my life—my family doesn’t get it.”

Sandra X. is a gorgeous forty-something recently divorced lady that has a fulfilling professional life and an affectionate family of four—her mother and three children. But no husband. And therein lies the source of her strange emotional frustration. Her family cannot picture her without the formal company of a man at all times.

In prehistoric times a woman that had not found a steady mate by the time she was thirty years old was dismissed as a “singleton” that had “to dress the saints.” And if a woman lost her husband after 50 years old she had to care for grandchildren. But times have changed dramatically and now any woman can have a new start at any age, be it 40, 50, 60, and even 70 years old. There are many artistic, sports, gastronomic, travel opportunities, etc., for someone that has the time and means. Moreover, she can find new friends and even a good companion in the new activity.

Sandra X. decided to learn how to paint, something she had wanted for years. Finally, she had the opportunity and the financial means to assist to a course, prepare a small atelier at home and network with people interested in art. As she felt too old to start bar-hopping to reboot her social life and meet men, she decided to visit art galleries with the company of another lady who had become a widow. They were both surprised to meet so many educated, interesting people in a city like Miami that until recently had been considered as a cultural and civic morass.

In big cities that are constantly renovating their socio-cultural matrix, the possibility of connecting with different people in exciting settings is much higher than in more suburban and rural environments where patriarchal prejudices still hold power. Initially Sandra X. avoided to have sexual relationships but eventually she fell madly in love with young bohemian painter 20 years younger and with a cute ponytail. Coming form an Hispanic family, she fears the reaction of her children to her choice.

Still undecided whether to break the news to her kin or not, she had nonetheless decided to rent a big apartment in the tony Wynwood neighborhood to install a bigger atelier and create an alternative home to enjoy her passionate relationship.

What do you think? Please tell us.

Don’t leave me alone.

 

CDC update on children with Zika

As a result of a forum convened with the American academy of Pediatrics and the American Academy of Obstetricians and Gynecologists, the Centers for Diseases and Control (CDC) published new clinical management guidelines for Zika infants. Ever since the Zika infection was recognized as a public threat, physicians have been reporting post-natal complications like eye abnormalities, incident microcephaly in infants with a normal head circumference at birth and diaphragmatic paralysis. This update used clinical data collected up to September 2017 and will be revised again.

Infants born to mothers with possible Zika infection and who exhibit some of the above-mentioned symptoms should be tested with specific serum and urine tests; if they come out negative, they should have a CSF sample tested for Zika RNA and IgM Zika antibodies. At age one month, they should have a head ultrasound, a comprehensive ophthalmologic examination and auditory brainstem audiometry.

The ophthalmologic exam should pick up any of the following anomalies:

  1. Microphthalmia
  2. Coloboma
  3. Intraocular calcifications
  4. Optic nerve hypoplasia and atrophy
  5. Macular scarring with focal pigmentary retinal mottling

The ABR audiometry must be done at one month because the Zika virus infection can produce sensorineural hearing loss; its late onset has not been documented.

As epileptic activity can be part of the Zika syndrome, the infants at risk must have a complete neurological examination to detect some subclinical EEG abnormalities. An MRI of the brain can detect subtle brain abnormalities like the following;

  1. Cortical thinning
  2. Corpus Callosum abnormalities
  3. Calcifications at the junction of white and gray matter
  4. Ventricular enlargement

As they grow, these infants must be periodically examined for clinical signs of increased intracranial pressure, an ominous sign of a developing hydrocephalus.

There is a large group of infants without clinical signs of congenital Zika and who were born to mothers with possible exposure to the virus in their pregnancies but without laboratory evidence of an infection that pose a clinical challenge for the medical personnel. There are some socio-economic variables like the lack of proper testing or inadequate laboratory facilities that produce false-negative test results. The CDC does not approve of further testing in these infants unless worrisome clinical symptoms appear later and subject to discussion with the caring personnel.

Serial ultrasound examinations can be cumbersome and expensive; the use of amniocentesis carries the certain risk of fetal loss and/or damage. Any testing must be a shared-decision between the professionals, patients and their families.

What do you think? Please tell us.

Don’t leave me alone.

 

The emotional dependence

– “Doctor…I need to consult my husband on everything—I depend on him.”

Paola X. is a successful physician that has settled in South Florida after completing her training in New York a decade ago. We met in an Italian-American social event a few years back and we have been friendly ever since. She is married to a very successful American professional and they have a nice family of four. However, her initial upbringing in a traditional Neapolitan family where the authoritarian figure of her father dominated even the secondary matters at home has marked her.

She has invested all her energies and time availability in the creation of a welcoming hearth for her husband and children, even though she is a very busy professional herself. She plans all their daily activities at home, being the perfect homemaker. However, all that dedication has come at a heavy personal price as she does not have any independent activity, let alone a supportive network of loyal girlfriends.

A rewarding loving relationship entails sharing a lot of time and activities with your partner, but do you have to share everything, all the time? There is a danger that any attempt of decoupling for the most menial task in a banal period by one partner might be construed as a sign of disloyalty by the dependent one. Individuals that have suffered unusual verbal and/or physical abuse as children are more likely to experience what psychologists call “anxiety of separation” in modern practices.

We all strive to love and be loved but the necessity of being always in the company of our partners can lead to great personal anxiety and undue stress in the couple. Moreover, to preserve the close relationship at all costs, the dependent individual can accept and endure various forms of abusive partners’ behavior. One of the sad tenets that we have found in the discovery of abused women is that they usually erroneously feel that “they need their partners”, delaying their rescue. We have witnessed how a few women have refused to press charges against physically abusive partners, even when the physician and/or social worker have helped them.

Sadly, the couple’s children can become hostages of these unhealthy relationships and in a few instances they are passive, suffering witnesses to intolerable levels of abuse.

What do you think? Please tell us.

Don’t leave me alone.

 

Disparities in access to Palliative Care

Access to good, timely and comprehensive Palliative care is one of the great advancements in modern medicine as it has improved the quality of life of patients and their families. However, there are still major disparities in its access, especially for members of vulnerable communities like Minority populations in the USA.

One of the most disseminated and fallacious “truths” circulating in the hospital corridors and medical offices in this great country is that Minorities, i.e. Blacks and Hispanics, do not care much about Palliative Care for socio-cultural reasons. It is true that disadvantaged members of society usually fear, with good reason, that they will be summarily treated and later abandoned by the medical establishment. They view the possibility of Palliative Care as an excuse to withhold necessary care. To complicate matters worse, many minority patients are deeply religious, for which they are confounded by the mixed messages emanating from their traditional churches.

Faigle et al. published an online article where they suggest that the culprit for this glaring inequity of access is actually the systems implemented in certain hospitals, using the data from the ICD-9-CM codes stored in the Nationwide Inpatient Sample (part of the Healthcare Cost and Utilization Project) They found that Minority patients received less PC than whites but also discovered that the same was true for all the patients admitted to largely Minority-serving hospitals.

In predominantly white hospitals., the researchers found that the median rate for the use of Palliative Care in post-Stroke patients was 8.5 per 100 ICH admissions but in mixed or largely Minority-hospitals the median usage rates were 6.3 and 2.5 per 100 ICH admissions respectively. The usage of Palliative Care after Ischemic Stroke was 2.2 per 100 admissions but it lowered to 1.5 in mixed facilities and a dismal 0.5 in largely Minority-hospitals. This data was controlled for demographics, comorbidities, socio-economic factors, hospital features and stages of the disease.

Important variables in the system were the implementation of sound institutional algorithms that could alert the medical personnel that the services were available.

What do you think? Please tell us.

Don’t leave me alone.