How my story began…
It all started years ago, February 2013 to be exact. I was in 8th grade and was studying hard for the my state standardized test, the FCAT. In addition, I was admitted into the incoming class of Pre-Medical Magnet students at my high school. Things began to change quickly. I realized when my mother was speaking to me one weekend at home, the words seemed like they weren’t registering in my head. I knew I had to say something. The next thing I remember, I was in St. Mary’s Children’s Hospital beginning to get better. I was admitted for over a week, studied on with multiple tests, and stuck with countless needles. I went home with no answer or explanation at all. This reoccurred two more times causing me to be admitted into Miami Children’s Hospital (ironically being my initials) before being flown to Boston Children’s Hospital for approximately ten days. After 7-9 days I began to feel better as usual. I look up to see my parents, nurses, and other medical staff looking back at me. My dad handed me his iPad for me to read an article with the title, “Kleine-Levin Syndrome.” As I read I start to break down crying, not because I realized I have a disorder but the fact that I finally now have an answer.
What is Kleine-levin syndrome?
Kleine-Levin Syndrome (KLS) is a rare neurological disorder, primarily characterized by episodes of recurrent hypersomnia, and a mixture of cognitive and behavioral abnormalities. During episodes, sleeping excessively can often last 16-22 hours per day. Though when awake, there’s a different story. One characteristic while awake is derealization. It’s the altered perception of the external world as if it’s unreal. Bringing about the feeling everything is a dream; thinking something is happening, but not knowing for sure; having sensation, but the inability to interpret and perceive; everything being fake and unreal. Another symptom is hyperphagia. This the over consumption of food. On the flip side, some patients eat and drink very little. Behavioral changes occur, and to encompass them, they can be described as compulsion and behavior similar to that of a child with autism. Cognitive disturbances also occur. These include things such as confusion, lack of concentration and attention, and memory defects. Abnormal speech is common as well. This includes becoming mute, without spontaneous speech, short sentences with limited vocabulary, speech being slurred and muddled, incoherent and childish stereotypical language, slow to speak and comprehend, and echoing questions. When an episode ends, most symptoms (if not all) resolve on their own and resume to their “normal” state. Although, some patients continue to experience some abnormality in-between episodes, and there is now evidence of long-lasting neurological impacts that could explain the abnormality that some experience in between episodes. Episodes may persist for days, weeks or even months, leading to the inability to attend school, work, or care for themselves. Affected individuals may go for a period of weeks, months or even years without experiencing any symptoms, and then symptoms reappear with little to no warning. Unlike the old-school idea, KLS episodes may continue to reoccur for many years beyond the 15-20 year mark. KLS robs individuals of pieces of their lives, one agonizing episode at a time.
Who gets KLS?
KLS is extremely rare, with an estimate of 1-2 cases per million worldwide. KLS typically begins during adolescence, but it may occur at a younger age and in adults. Literature seems to suggest an association of Jewish predisposition, but KLS presents itself in all races and ethnicities, and affecting both males and females.
What causes KLS?
The etiology is idiopathic (unknown). One suggestion is autoimmune mechanisms. Many patients report having an infection preceding their initial onset of KLS symptoms. In some cases, there is an increased frequency of the gene named HLA-DBQ1, among many others, which has its role in recognizing proteins of foreign invaders and triggering a response to attack it. The Human Leukocyte Antigen (HLA) complex helps the immune system distinguish the body’s own proteins from proteins made by foreign invaders such as viruses and bacteria. Autoimmunity may be influenced by viral factors that cause B cells and memory T cells to produce autoreactive antibodies that may cross the blood brain barrier. Some patients have experienced positive outcomes after administration of prednisone/methylprednisolone , which is an immune-suppressant. The combination of HLA frequencies, onset after an infection, and successful treatment, are the basis for the autoimmune hypothesis. Another suggestion is an underlying hypothalamus pathology, since the thalamus and hypothalamus are critical in regulating sleep, appetite, and sexual behaviors. However, there hasn’t been consistent abnormalities found. MRI studies are unremarkable, EEG slowing has been noted in most cases during an episode, but many fMRI studies have shown diffuse hypoperfusion (decrease in blood flow, causing decrease in activity) mostly on the thalamic and frontotemporal areas. In a few cases, abnormalities in serotonin and dopamine (two chemical messengers in the brain) metabolism have been reported, suggesting a neurotransmitter imbalance in the serotonergic or dopaminergic pathways. Most cases have unremarkable findings and there is yet to be a biomarker specific to KLS. Research is being done around the globe, including California, France, China, Florida, and Georgia.
How is it diagnosed?
Diagnosis of is very difficult because there are no symptoms that are entirely distinct only for KLS. Therefore, KLS is a diagnosis of exclusion and is entirely clinical. According to the International Classification of Sleep Disorders, it belongs to the category of recurrent hypersomnia. People with KLS are often mistakenly diagnosed with a psychiatric disorder. This is because the periods of somnolence (sleep), hyperphagia, and withdrawal can mimic severe depression. Some people experience a brief period of high energy following episodes, which looks like a manic episode, which can lead to patients being incorrectly diagnosed with bipolar disorder. There can also be a number of other mood symptoms or perceptual disturbances which mimic primary psychiatric disorders. Furthermore, KLS may look similar to Autoimmune Encephalitis. There is no definitive tests, laboratory nor imaging, to diagnose KLS, but it is important to have a provider that is willing to look at a patient on a case-by-case basis, catch up on current literature, and not always work by the book.
How is it treated?
There is no definitive treatment for during episode, nor for the inter-episodic (between episodes) period. Various medications have been used during episode in many case reports and found to be no consistent benefits from any one of the drugs. Various stimulants, including methylphenidate, modafinil, ephedrine, methamphetamine, amphetamine, can be used to treat sleepiness, but unfortunately do not improve the cognitive abnormalities nor other elements of the altered mental state. Lithium was also tried during episode. This is a type of mood stabilizer. Lithium significantly improves abnormal behavior and recovery of symptoms for some patients. One of the possible causes could be similarities between Kleine–Levin syndrome and bipolar disorder. During inter-episodic period, various mood stabilizers, such as lithium, carbamazepine, valproate, phenytoin, and phenobarbital, can be attempted. Of these treatments, only lithium has a reported response rate significantly higher than the others within its kind. There has been short term beneficial responses shown with Clarithromycin. Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter (brain cell messenger) in the brain with well-known effects on sleep/wake cycle regulation. The GABAA receptor is the site where sleep-inducing drugs have their effects, and recent research suggests GABAA receptor antagonists (goes against the original function of the receptor) may be useful in the treatment of hypersomnia. Clarithromycin, an antibiotic with GABAA receptor antagonistic properties, been beneficial in the treatment in some cases. Another treatment option is an immune-modulator, such as CellCept. Given the possible autoimmune mechanisms in KLS, CellCept is a valid attempt and is much safer than classical steroids, like Prednisone. Furthermore, it has been successful in several autoimmune neurological diseases. Mood stabilizers, antiepileptics, stimulants, immune-modulators, antibiotics, high vitamin D3, etc., have all been attempted. One treatment may work for one person, but not for another. It is important to have a supportive provider that is willing to “think outside the box,” as a patient desperately wants this disorder to be mitigated.
KLS forces a radical change in all aspects of life from friends and family, to life-long goals. Patients need almost twenty-four hour care and assistance with everything when in an episode, even the most basic daily tasks, such as eating and brushing teeth. Unfortunately, this disorder is something that very limited medical professionals know about as it isn’t something that is stressed in any curriculum. Personally, I got lucky enough that the provider that diagnosed me remembered seeing an example case on a board question. The rarity of the disorder creates a toll on funding for research. Internationally, there are 5,000 – 10,000 known cases, giving it the presence roughly 0.00005% of people in the world. Many people aren’t diagnosed, are misdiagnosed, mistreated, and this ultimately causes unneeded harm. I believe awareness is acquired not only through the memory of one’s story, but with having the knowledge about this disorder. Awareness in schools, medical professions, and the general public is needed in order for light to be shined on this incredible unknown.
Michael C. Hamper was born and raised in sunny, South Florida. His medical and scientific endeavors very young with many acute and chronic medical issues, and he is driven to pursue a career in medicine and research. Mr. Hamper is currently a senior at Florida Atlantic University in Boca Raton, FL. He will be graduating in April 2021 with a Bachelors of Science degree in Neuroscience and Behavior, Magna Cum Laude, Honors distinction.
Continuing with academics… Mr. Hamper is the lead of several research projects. Few of them include the investigation of the potential therapeutic use of natural anti-cancer marine compounds against various cancers, including prostate, lymphoma, breast, neuroblastoma, and glioblastoma. Furthermore, he is passionately leading neuroimmunology research on the rare neurological disorder Kleine-Levin Syndrome. He has put together a team with international recognition, consisting of a biochemist, immunology, neurophysiologist, neuroimmunologist, and neurologist and sleep disorder scientist. The mission of this is to investigate the potential autoimmune mechanism of KLS in a way that has yet to be done for this disorder.
Mr. Hamper is also very much busy with things outside of the classroom and laboratory. Ever since attending Palm Beach Gardens High School in the Pre-Medical Magnet Program, he was “hooked” on competition in the internationally known organization, HOSA: Future Health Professionals. Upon entering university, he poured himself into the organization chapter at FAU and quickly became a leader. Mr. Hamper is currently the President of HOSA, starting this leadership in 2019, and providing many local and state opportunities to his fellow members. After graduation, he will be acting as Senior advisor for the chapter.
Another thing about Mr. Hamper is that he enjoys teaching others. He is an Organic Chemistry Teaching Assistant and has been leading and teaching organic chemistry to upwards of 120 students each semester for what is now his 5th semester teaching. He prides himself on teaching material in a way that is broken down in a way for students to understand, making concepts of what is already difficult course, much easier.
Despite everything he has going on, he makes sure to remain human and give time to himself. Mr. Hamper enjoys his favorite show, The Office, training in the martial arts of Tae Kwon Do and Jiu Jitsu as a 2nd degree black belt, hitting the golf course, skydiving, and relaxing with friends and family.
Michael Hamper’s plan is to become an EMT working in the ER while continue his research publishing on his Cancer and KLS project, matriculate into medical school in 2022, and establish a career in medicine in the field of neuroimmunology or neurosurgery.
“Success is not final; failure is not fatal. It is the courage to continue that counts.” – Winston Churchill