Posted by Daniel Rubio, Drexel University College of Medicine Class of 2014
“A man” obsessing over “bats”…
“A man” eating “bats”…
The patients above are displaying symptoms resulting from a disease known as Lytico-Bodig Syndrome (LBS), a neurologic disease resembling amyotrophic lateral sclerosis (ALS/Lou Gehrig’s Disease), Parkinson’s disease, and Alzheimer’s disease. The country with the greatest number affected is the US territory of Guam. In fact, between the 1940-1960 it was the leading cause of death among the Chamorro people, a tribe found on the island of Guam. The afflicted were usually between the ages of 25-40 years of age.
Although yet to be proven, it is believed that the high incidence of LBS is due to the consumption of fruit bat, a cultural delicacy on the island. These fruit bats feed on specific fruits containing high concentrations of an altered amino acid called beta-N-methylamino-L-alanine (BMAA). BMAA is a known neurotoxin and is believed to be the cause of LBS. BMAA is a protein building block that is incorporated into neuronal proteins to produce an abnormal form that creates clumps with neurons resulting in their dysfunction and death.
I addition to the high concentrations found in the fruit bats on the island of Guam, multiple sources have been proposed leading to BMAA exposure within the United States. Certain bacteria in fresh and salt waters produce BMAA; and, fish and crustaceans will concentrate BMAA within their tissues when they consume the bacteria as part of their normal diet. It is believed that human consumption of fish and crustaceans in at-risk areas might increase the incidence of neurodegenerative diseases, like Alzheimer’s, Parkinson’s, and Lou Gehrig’s. This association has been seen in many areas within the United States, especially around the gulf regions and around large bodies of water. Click here for more details about this.
Presenting symptoms exist along the continuum of lytico-bodig. Patients on the lytico spectrum present more like ALS/Lou Gehrig’s disease. These patients have muscle wasting/atrophy and accompanying weakness, paralysis of mouth and tongue, and an inability to swallow resulting in choking to death. Over time, paralysis involves the breathing muscles requiring mechanical ventilation to help the patient breath and to prevent choking on secretions. Lytico patients remain aware of their deterioration. The form of LBS is fatal in all cases.
On the other end of the spectrum, patients with bodig presentations look more like Parkinson’s disease and Alzheimer’s disease patients. Bodig patients present with “freezing” with progressive immobility with loss of starting purposeful movement and loss of spontaneous movement. Progressive dementia with loss of speech and irrational behavior, including violence and rapid fluctuations in mood, are common. Over time, patients are left in stiff and immobile postures with inability to speak and swallow.
Currently Lytico-Bodig syndrome is diagnosed based upon appropriate history and physical exam by a neurologist. Definite LBS is declared in post-mortem autopsy. However, there is research being done to develop rapid tests using cerebral spinal fluid analysis.
Treatment is mainly supportive as is based upon symptoms present, whether it’s Parkinson’s, Alzheimer’s, ALS, or a combination of the three spectrums of diseases. The more the symptoms resemble Lytico, the greater the mortality: in patients with predominantly lytico-type symptoms the disease is practically 100% fatal.
Put simply, some human cells can regenerate:
However, many human cell lines, including central nervous tissue, can not regenerate:
Human stem cells can go through numerous cycles of cell division while maintaining the undifferentiated state, but can still differentiate into specialized tissues like nerve cells:
When the appropriate stem cells are injected into injured tissues they will multiply, develop, and repair CNS injuries – at least, that’s the theory:
The Phase II (dose escalation) trials began in September 2013 in Michigan and Atlanta, and aims to recruit 15 patients for 5 different dosing protocols, and will look at efficacy:
Click here to find out more, and watch this space for results.
Amyotrophic lateral sclerosis (ALS), sometimes referred to as “Lou Gehrig’s Disease“, is a progressive neurodegenerative disease that affects motor nerve cells in the brain and the spinal cord ultimately leading to muscle paralysis.
The diaphragm is a large muscle that moves air across the lungs to facilitate gas exchange and oxygenation of the tissues:
The diaphragmatic pacing (DP) system bypasses the degenerated phrenic nerves in ALS, and provides direct electrical stimulation to the diaphragm, facilitating enhanced ventilation.
So we know we can electrically stimulate the weak or paralyzed diaphragm and make it contract.
Here is a link to a recent summary of studies that have looked at DP for hypoventilation in ALS:
Data presented to the FDA in 2011 included 106 ALS patients who had undergone the surgery.
DP patients lived 9 months longer than a historical cohort of ALS patients with respiratory difficulties treated with NIPPV.
Unlike NIPPV, DP patients do not have to use a mouthpiece or mask.
However, the serious surgical complication rate from the procedure was 3.5%, 26% patients report mild-moderate discomfort from the electrical stimulation, and there were many technical problems including broken electrodes.
In ALS, unlike in spinal cord injury, the denervated diaphragm muscle will ultimately become inexcitable, rendering the DP system ineffective.
DP surgery costs about $20,000, compared to <$1000 for a NIPPV system.
But before you sign up for DP,
Consider these facts:
DP is FDA approved as a medical device not as a therapy.
Many neuromuscular physicians are calling for real outcome data before widespread adoption of this invasive and expensive interventional procedure. In response to these concerns, the Muscular Dystrophy Association (MDA) and ALS Association (ALSA) have co-sponsored a prospective study to determine whether the DP system in effective or not.
Finally, we know that ALS patient care varies at different centers around the country. However, we don’t know how many ALS patients are getting their FVC measured or being assessed for hypoventilation appropriately. We hope that the new MDA sponsored clinical registry will answer this question.
Click here to find out more about hypoventilation in neuromuscular diseases.
Click here to link to a podcast about DP in ALS.
Click here to find out more about the DP system from the device manufacturer.
Click here to find out more about the DP clinical trial.
Each lung is composed of >300 million tiny membrane bound sacs of air sacs (alveoli) which if spread out would cover a piece of ground roughly the size of a tennis court. The purpose of this giant membrane is to exchange oxygen from the air for carbon dioxide from the blood stream.
Treatment includes adding extra oxygen to the air to make this process more efficient.
However, gas exchange across the alveoli can only occur if fresh air is brought into the lungs, and stale air is moved out, a process known as ventilation. The diaphragm and muscles of the chest wall act like a giant bellows to make this happen:
Early neuromuscular respiratory muscle weakness causes nocturnal hypoventilation. This is because the weakened diaphragm is even more inefficient when laying supine in bed with the stomach contents pressing up on it.
Nocturnal hypoventilation presents with daytime sleepiness, early morning headaches, fatigue, and impaired cognition.
Click here to take an on-line test, and find out how sleepy you are during the day. If you score 10 or higher, you might have a problem!
Nocturnal hypoventilation is best treated using a non-invasive respirator at night, either with a face or nose mask:
Other patients use a negative pressure respirator vest, or cuirass, which requires the patient to wear an upper body shell attached to a pump which actively controls the respiratory cycle:
Neuromuscular respiratory failure also leads to an ineffective cough, which in turn predisposes patients to aspiration, retention of secretions, or pneumonia. Affected patients need to learn to use the cough assist machine when they get a minor respiratory tract infection to help them clear their secretions and prevent pneumonia:
More severe neuromuscular ventilatory failure leads to rapid shallow breathing, accessory respiratory muscle use, thoracoabdominal paradox (inward motion of the abdomen during inspiration), and ultimately high blood levels of carbon dioxide.
In these cases, respiratory support is needed day and night.
Some patients can continue to use non invasive respiratory support, sleeping with a face or nose mask, and using a mouth piece intermittently during the day:
Others cannot tolerate noninvasive ventilation or have anatomic abnormalities that preclude fitting of noninvasive ventilators. Some disease, such as advanced ALS and Duchenne muscular dystrophy, affect the upper airway muscles as well as the diaphragm, impairing swallowing and compromising airway protection from aspiration. These patients can chose to be managed with invasive respiratory support using a tracheotomy and conventional ventilator.
The Neuroscience Institute at Monmouth Medical Center is proud to announce the opening of its brand new out-patient clinic space on the 4th floor of the Wimpfheimer building, which will will be the home of many new innovative programs.
This historical building was erected in 1919 with money donated by board of trustee member Charles A. Wimpfheimer, in memory of his 19-year old son Jacques, who when stricken with pneumonia while in military service requested that he be given the same treatment as the other privates, and as a result was sent to a ward in a Hoboken hospital, where he died.
Click here for directions to Monmouth Medical Center.
Once you arrive, enter the hospital from 3rd Avenue (1), park (2) and enter the hospital via the Radiation-Oncology Entrance (3). Register at the desk:
You will be directed to elevators that will bring you up to the 4th floor (BBR4), where you will pass through a nursing evaluation, then proceed to out brand new out-patient space on Wimpfheimer 4.
Multifocal motor neuropathy (MMN) with conduction block is an acquired immune-mediated demyelinating neuropathy, which causes slowly progressive weakness, fasciculations, and cramping. It can resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but distinction is important since MMN usually improves with immunosuppressive treatment.
MMN is more common in men than women with a mean age at onset of 40 years (range of 20–70). The most common initial symptoms are wrist drop, grip weakness, and foot drop. Weakness progresses asymmetrically, but usually remains more prominent in the arms than in the legs. Weakness is typically more pronounced than would be suggested by the degree of muscle atrophy present. Affected patients also complain of muscle cramps and fasciculations. Tendon reflexes are reduced in affected regions. Sensory complaints are unusual.
These symptoms and signs from MMN are very similar to those seen in early ALS, and many patients are initially misdiagnosed with this disorder. MMN can usually be distinguished from ALS by its more slowly progressive disease course, the absence of upper-motor-neuron signs such as spasticity and hyperreflexia and the lack of difficulty with speech and swallowing.
However a carefully planned and executed electrodiagnostic study (EMG) is critical for distinguishing these disorders. MMN is a demyelinating neuropathy, while ALS is an anterior horn cell (motor neuronopathy) which causes secondary axonal degeneration of the motor nerve. When one suspects MMN clinically, identifying partial motor conduction block is critical in confirming the diagnosis.
The presence of high titers of antibodies to GM1 ganglioside can also be useful for confirming the diagnosis of MMN, but are only present in 20-60% of patients, and are rarely present in ALS patients, underscoring the importance of clinical suspicion and the EMG for making the diagnosis.
MMN is an immune mediated disorder and strength can recover after repeated treatments with intravenous immunoglobulin (IVIG), whereas ALS does not respond to this or any other treatment, hence the importance of distinguishing these 2 disorders:
Disease MMN ALS
Distribution of weakness Asymmetric,Arms Ultimately generalized
Upper motor neuron findings Absent Usually present
EMG Conduction block Motor axonal loss
Anti GM1 Ab 20-60% 10%
Response to IVIG Yes No
The clinical pictures below are from a patient with longstanding generalized weakness that I encountered several years ago. The first picture shows his severe upper limb atrophy (and weakness):
His EMG showed conduction block, suggesting MMN:
And the second picture showed the clinical improvement that had already occurred after 6 monthly treatments with IVIG:
Obviously it is important to at least consider this treatable disorder in all patients with suspected ALS or motor neuron disease, and it is very important to see a neurology specialist with additional training and certification in neuromuscular medicine and/or electrodiagnostic medicine. Click here or call 732 923-5576 to find out more about the Central Jersey MDA and Neuromuscular Center at the Monmouth Neuroscience Institute.