Friday, May 13, 2011

0 Lyme Brain: Diagnosing Early Neuroborreliosis

While looking around You tube for something interesting and educational to share with my minions readers, I came across this little two minute video (no audio):


It really got my attention, because I suspect that long-term complications that come on the heels of a Lyme disease infection could be because a certain number of people are either misdiagnosed to begin with (and thus treatment is delayed) - or they are under-treated for Lyme disease in the first place when they have neuroborreliosis.

Throwing 10-14 days worth of doxycycline at an infection that is passing or has passed the blood-brain barrier is not going to cut it,  and this is why IV Rocephin for 30 days is the baseline treatment for early neuroborreliosis.

There has been some debate over what dose of which antibiotic can be used to treat neuroborreliosis, but putting that debate aside, one big step in treating it properly is being able to diagnose its presence early.

So when I found this little video, I had to know more...

N-acetylaspartate (NAA) concentrations in the brain are decreased if there is damage.
I noticed there was a name on the lower lefthand corner: Dr. Oded Gonen. Tiny, tiny print, but there.

So I looked that name up to see if I could learn more about him. Maybe you're reading this and you already know about him, but I suspect a number of my readers may not.

Dr. Oded Gonen is working for the clinic that Dr. David Younger began - a clinic mentioned in Cure Unknown:
A new program led by neurologist David S. Younger M.D. will open its arms to patients and their treating doctors, wielding science to get a handle on the disease. 
Pamela Weintraub, Cure Unknown, Inside the Lyme Epidemic, 2nd Edition, 2009.
And so, the Lyme Neuroborreliosis Program was born in New York City, and Dr. Onen Gonen is one of the researchers on staff who is conducting his own clinical trials on neuroborreliosis.

The clinic has this to say about neuroborreliosis symptoms and treatment:
"The spectrum of neurological and behavioral disorders ascribed to Lyme disease has been the subject of intense debate. Three clinical syndromes are seen in such increased frequency that their presence alone or together should prompt consideration of Lyme neuroborreliosis in a given patient. They include meningitis, painful polyradiculitis, and cranial neuritis (most commonly a facial palsy). It is important to recognize them and potentially other central, peripheral, and autonomic nervous system manifestations, abbreviated CNS, PNS, and ANS, because they occur early in the infectious illness, lead to a vigorous immune response, and their symptoms resolve more quickly with early institution of antibiotics. There is still debate about encephalopathy, cognitive impairment, and neuropsychiatric involvement in Lyme disease, and the frequency of chronic and late Lyme disease in treated individuals. Notwithstanding, the vigorous immunological response triggered by the Borrelia spirochete infection appears to be a potent factor in the perpetuation of symptoms long after effective treatment has been administered and the infection has been presumably eradicated."
Whatever your beliefs about the efficacy of long-term antibiotic treatment, early treatment of neuroborreliosis is particularly important, but one of its stumbling blocks has been accurate diagnosis.

As mentioned in this blog before, only a small percentage of early neuroborreliosis patients are diagnosed using a positive CSF culture or blood tests - often a good clinician has to pay close attention to symptoms and history to pin down the diagnosis.

Even Dr. Younger has suggested a combined testing method for neuroborreliosis and Lyme disease in general, in his 2010 publication, Lyme Neuroborreliosis: Preliminary Results from an Urban Referral Center Employing Strict CDC Criteria for Case Selection.

Dr.Younger stated:

"A two-tier test approach for active disease and previous infection with the demonstration of a significant change in IgM or IgG antibody response to B. burgdorferi in paired acute- and convalescent-phase serum samples, examination of diagnostic levels of IgM and IgG antibodies to the spirochete in CSF, and isolation of B. burgdorferi from CSF are recommended to improve the diagnostic accuracy of serological testing in Lyme disease, including LNB."

This is better than just giving someone with a tick bite and rash an ELISA and then calling it a day when it comes back negative if they are symptomatic. It's not perfect - but it's an improvement.

Dr. Younger further wrote in his summary:

"The management of LNB remains controversial as to the timing and duration of oral and intravenous antibiotics. The occurrence of peripheral neuropathy, dysautonomia, and encephalopathy years later after adequate antibiotic therapy underscores the selective vulnerability of the nervous system to the immunological effects of B. burgdorferi infection, although the exact mechanisms remain uncertain."

Maybe further test development could at least uncover more cases earlier, even as the mechanisms are said to be unknown.

Right now Dr. Gonen is working on a new test for diagnosing neuroborreliosis. He's conducting clinical trials on the use of proton magnetic resonance spectroscopy (1H-MRS),  which detects metabolic disturbances in the brain - even without showing an MRI abnormality such as a visible lesion. In the trial, he intends to examine metabolic parameters in neuroborreliosis patients.

The parameters he is examining are demyelination, oxidative, and neuronal damage processes indicated by monitoring their surrogate markers: creatine, chloride, lactate and N-acetyl aspartate (NAA).

Of these markers, N-acetyl aspartate or NAA is specific to the brain, being the second-most-concentrated molecule in the brain after the amino acid glutamate. NAA is a useful indicator for disease, as it gives off the largest signal in magnetic resonance spectroscopy of the human brain - and the levels measured are decreased in numerous neuropathological conditions ranging from brain injury to stroke to Alzheimer's disease.

1H-MRS is also used to measure the impact of HIV on the brain and in Lupus and MS studies. It's good to know that someone is conducting more tests using this technology if it can help diagnose early neuroborreliosis - so far, I've only found the below study in the use of 1H-MRS for neuroborreliosis, and it may yet be another tool in the Lyme toolbox.

Related studies:
Proton MR spectroscopy in neuroborreliosis: a preliminary study
http://www.springerlink.com/content/4lb8ba29yycv136e/

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