Lyme Science Blog
Apr 18

Subacute parkinsonism as a complication of Lyme disease

Comments: 64
1
Visited 140 Times, 3 Visits today

by Daniel J. Cameron, MD MPH

The article describes a 55-year-old patient with a 2-month history of chronic neck pain with progressive marked asthenia. “Clinical examination revealed a dysarthria which disappeared in less than 1 hour, a left upper limb cerebellar ataxia and a bilateral asymmetric mild akineto-hypertonic parkinsonism,” according to Pische´ from the Department of Neurology, CHRU Strasbourg, Strasbourg Cedex, France. [1]

The second case involves a 63-year-old woman who developed a rapidly deteriorating severe walking disorder over a 6-month period. “Clinical examination revealed lower limbs weakness, increased reflexes, bilateral extensor plantar, and dysuria, as well as a left akineto-hypertonic syndrome.” Facial palsies were also described.

Brain MRIs showed vascular demyelination, typically seen in inflammatory, infectious, drug induced, or paraneoplastic vasculitis conditions.

Physicians suspected both patients suffered from neuroborreliosis. They each presented with an abnormal DaTscan, a specialized imaging technique that allows doctors to capture detailed pictures of the dopamine neurons in your brain.

“In both cases, DaTscan demonstrated apresynaptic dopaminergic denervation which has been associated with striatal ischemic lesions due to Lyme probable vasculitis,” explains Pische´.

The DaTscan (GE) has been used in Parkinson’s disease to “allow physicians to provide accurate clinical management of the patient and prevention of unnecessary medications and procedures,” says Seifert from Florida Atlantic University. [2]

Both patients, presenting with subacute parkinsonism and an abnormal DaTscan, were diagnosed and treated successfully for Lyme disease. “The two patients reported here, who developed, fulfilled the diagnostic criteria for neuroborreliosis: no past history of neuroborreliosis, positive anti-BB antibody index, favorable outcome of neurological signs after specific antibiotic treatment, and absence of other diagnosis,” according to Pische´. [1]

The first case of subacute parkinsonism resolved with a 21-day course of 2 g per day of ceftriaxone without the need for dopaminergic treatment. The second patient required a second 21-day round of ceftriaxone, along with 3 months of corticosteroid therapy (60 mg/day) and Ldopa/carbidopa (300 mg/day).

Acute or subacute parkinsonism, according to the authors, can be a complication of Lyme disease, as demonstrated in these two cases. Therefore, Lyme disease should be discussed when patients living in endemic areas present with basal ganglia MRI lesions.

“In front of an acute or subacute parkinsonism, especially in endemic region, neuroborreliosis should be discussed in case of associated headache, multisystemic neurological signs, or MRI basal ganglia vasculitis or inflammatory signs.”

The authors cautioned, “Lyme blood or CSF serology should not be asked for, even in endemic region, in case of progressive parkinsonism without any basal ganglia MRI lesions.”

References:

  1. Pische G, Koob M, Wirth T et al. Subacute parkinsonism as a complication of Lyme disease. J Neurol, (2017).
  2. Seifert KD, Wiener JI. The impact of DaTscan on the diagnosis and management of movement disorders: A retrospective study. Am J Neurodegener Dis, 2(1), 29-34 (2013).

Related Posts

64 thoughts on “Subacute parkinsonism as a complication of Lyme disease”

  1. I have had Lyme since 1996. First big episode in 2001. Went to LLMD, treated for 1.5 year with oral abx. DR. B protocol.
    In 2003 had MRI done and in the results it noted the following.
    There is minimal subtle periventricular increased signal in the periventricular white matter, particularly adjacent to the occipital horns of the lateral ventricle and in the temporal -occipital regions. Several tiny periventricular spaces are noted in the basal ganglia.
    Does this correlate with this article?

    1. This paper reminds doctors on the difficulties interpreting the causes of specific finding on scans. I encourage my patients to seek consultation with specialists to weight different diagnosis and treatment options.

  2. Dr. Daniel Cameron
    Marta Sanimill

    Having Lyme, and have gone through 30 days of dioxacycline(SP), then after 30 days of intravenus antibiotic because of Bundle branch block as Lyme attacked one chamber of my heart. I am now experiencing parkinsonian like symptoms with electric shocks racking my body, extreme imsomnia, extreme restless leg syndrome, and at times in full body shakes. They come and go however the electric choks continue inrelentingly. I need help. No one understands. The ER actually wanted to give me a mental consult.

  3. I am wondering when these diagnoses will collapse: Multiple Sclerosis, Parkinsons Disease, ALS, Chronic Fatigue Syndrome, Fibromyalgia ? They only describe how the patient presents with his symptoms ! There is not a clue about the cause!

  4. Marta – I know how you feel. I am an otherwise healthy 59 yr old. My dad lived to be 93 years old and my mom is still alive at 93 years old. I have not been diagnosed yet but Gait Ataxia and Parkinsonism have been mentioned. Sometimes I just need some relief. I am scheduled for my 2nd MRI in a couple of weeks. I will see what they have to say then.

  5. I’ve been taking Doxycycline in “pulse therapy ” mode (three days on, four days off) for a couple of years now. Still two active Lyme bands on blood tests. It this going to be the drill for the rest of my life, or is there hope a more permanent solution will be found some day?

  6. Is it possible to get some more information regarding the treatment of the second patient? I fit the profile and am trying to get my neurologist and Lyme specialist to have a dialogue as I would like to try this treatment approach. I was very excited by this article as I bave been trying to find a connection between Lyme disease and an irregular Dat scan.

    Many thanks

  7. My husband has Lymes and it is affecting his balance. It also attacks his joint etc. I was wondering what to do for him. I have tried different supplimentes but they don’t seem to be helping. I am afraid that the Lymes will cause brain damage. The last three weeks he is getting more unbalance that the last year. He has to have a cane or me to balance him. At times as a minister he is unable to make sense of what he reads. Can this lead to Parkinson’s???
    Help please

    1. I am sorry to hear your husband is ill. It can be difficult to find the cause of cognitive issues and balance problems. The blog reminds us to add subacute parkinsonism to the list of potential causes. There is always the possibility he could suffer from both tick borne conditions and Parkinsonisms.

  8. I have had LD for about 15 years. I have had four recurrences resulting in a new disease 1. Fibromyalgia 2nd= Asthma 3rd= Lupus 4th= Parkinson’s. None of these are genetically in my family. What test are any of you getting that shows positivity? When I mention Lyme to any Dr. but my Lyme specialist I get “That look”.
    So far, the medicine I am taking- the cure is worse than the disease.
    I am starting to realize that Lyme always wins.

  9. My mother was diagnosed with Lyme in September of 2015 and then Parkinson’s in November of the same year. No telling when exposure to the Lyme happened but I’m concerned that long-term Lyme symptoms may be complicating her Parkinson’s symptoms – or maybe causing them? Having a hard time getting her PCP, neurologist and the infectious disease department at the hospital where she is treated to discuss this with me. Her response to the Parkinson’s meds have been marginal and her symptoms are progressing. I would like to get her retested for a Borrelia infection to rule out interference by the Lyme / make sure we are pursuing the correct treatment. Tips on how to get the doctors to take this seriously?

    1. The tick borne tests are not as reliable as we would like. We often have to use clinical judgment. Parkinson’s disease relies in part on clinical judgement. It is always possible to have both conditions as they are both common.

    2. Good luck, many doctors still deny Lyme. My sisters-in-law was diagnosed with Parkinson’s at 58 because her mother had Parkinson’s . 19 years later and many clinical trials with Johns Hopkins, and non typical symptoms her daughter sent her urine for Lyme DNA and it was positive. Too much damage, not much better with IV treatment.

      1. I am waiting on more data on the reliability of the urine DNA test. I have seen patients in my practice who have both parkinsonism and Lyme disease as they are bot common illnesses. There are co-infections in a tick that do not respond to IV.

  10. I ended up it the hospital for acute angle closure glaucoma due to starting Lexapro. I had fluid on my brain. Many procedures have been done over the last 2 years. Was tested for Lyme which came back saying I had had Lyme for a year plus. Took Doxycycline for 8 months. Joints got better, now everything is worse. The shaking, tremors, stress, anxiety…… Taking anxiety meds but it still doesn’t stop these symptoms. Trying easy yoga. Cannot stand on one foot or the other with out holding on to something. Many other issues but is this part of the Parkinson’s issue. Any other tests I can ask my Dr. for? Or do I just settle with it’s Lyme since neither seems to be curable?

  11. My husband has Lyme disease and they say he has Parkinson’s but the meds really aren’t doing anything and I’m watching the man I love disappear. I would really like to know about this test/scan. He did 1 month oral and 1 month pic line and then he was put on Parkinson’s meds. He did have one brain scan that showed white matter. We are in northern Wisconsin.

    1. Both Lyme disease and Parkinsonism are common illnesses. I reviewed the case as it examined whether the two illnesses could ever be related. It sounds as if the doctor considered a tick borne illness in your case. I do not know anyone in the area to help.

    2. Marlene, I am from Central Wisconsin and have the same predicament.
      Did you find someone to help you?

      Michelle

    3. There are some doctors and nurse practioners that are considered Lyme Literate that will help you treat Lyme and the co-infections which will not respond to the same antibiotics given for Lyme. Many people are co-infected. My Lyme literate Nurse Practitioner in northern WI says “everybody in WI has Lyme”. I got Lyme, Babesia, and Bartonella there visiting the Hayward area. My kids also have these diseases. They can mimic so many other diseases and most practioners are clueless!! Real world chronic Lyme, Babesia, Bart, etc is not taught in med school. Very complicated, but you can find your answers in researching these diseases!

      1. BTW I have not concluded that everyone has Lyme disease. Everyone is at risk of Lyme disease. I am primarily concerned with individuals with Lyme disease who have been misdiagnosed or who are not aware they have Lyme disease.

    4. Marlene, I am in Wisconsin and have a similar situation. Except it’s me who has the neurological problems.
      I know it’s been 4 years since your post, but I was wondering if you had an update.

  12. I just got a 2nd opinion at major University hospital and its suspected my parkinsons diagnosis may actually be neuro lyme. I have tremors especially in right arm and now have frozen shoulder as well. Cefdinir seems to be helping clear brain fog and fatique. Also on carbidopa but not really helping tremors yet. Tested positive for western blot lyme (two times once early and now again) and also positive anaplasma. Been on oral abx for two years and had 21 days of Rocephin early on. Docs suggest iv abx again or maybe ivig might help. Also suggested lumbar puncture. JR

  13. I was diagnosed as Parkinson’s November 2019. I had a MRI which didn’t show any abnormalities. But my Neologist says symptoms show Parkinson’s . I just turned 60 and don’t want to waste a year taking Parkinson’s medication. I took it for a month and seen no improvement. Now he’s saying try a stronger dose. How do I get them to test for Lyme disease?

      1. My general physician did a blood test and results were negative. I’m still not convinced it’s Parkinson’s. I recently developed numbness and tingling in my ride side extremities. Which is not a sign of PD. I started taking the meds to see if it makes a difference. I’ll give it 2 months. Do you know of any doctor in southern Michigan whose expertise is Lymes? I would I find one?

        1. You will find several websites that have directories to help you e.g., Global Lyme Alliance, Lyme Disease Association and ILADS. You can also call my office in New York at 914-666-4665 to find out if a teleconference would work.

        2. My husband also was diagnosed with PD – neurologist and FAmily physician refuse to test for Lyme and when the subject was brought up they immediately dismissed me! His symptoms have been present since his mid 30s- he was on the levo-carb for over a year (4 pills daily) with NO difference except severe side effects! How do I force the doctor to test him for Lyme?!? It’s like they do t even want to treat you after you ask about Lyme! Very interested to see if you get any results or positive feedback! When I first met him 20 years ago – I dug what I thought was a tick out of his back- however by they it had been burrowed into the skin of his back for so long you couldn’t tell if it was a tick or not! But he still has a hole in his back where the sucker burrowed in there!! Told all of this to the neurologist and he basically yelled at me- this is PD you need to deal with it!!

        3. My husband also was diagnosed with PD – neurologist and FAmily physician refuse to test for Lyme and when the subject was brought up they immediately dismissed me! His symptoms have been present since his mid 30s- he was on the levo-carb for over a year (4 pills daily) with NO difference except severe side effects! How do I force the doctor to test him for Lyme?!? It’s like they do t even want to treat you after you ask about Lyme! Very interested to see if you get any results or positive feedback! When I first met him 20 years ago – I dug what I thought was a tick out of his back- however by they it had been burrowed into the skin of his back for so long you couldn’t tell if it was a tick or not! But he still has a hole in his back where the sucker burrowed in there!! Told all of this to the neurologist and he basically yelled at me- this is PD you need to deal with it!!

    1. Get them to sign off on an Igenex test out of network or buy one yourself. A dr that is Lyme literate has to be able to understand the info though. This test saved me after suffering for 15 yrs!

  14. My husband has had the bullseye bite but was told it was nothing. They removed the tick as well. It was not long before he began to lose weight and seemed to weaken as well as have some balance issues and began shuffling. When he alerted his physicians to the weight loss they told him most people we see are obese. You are in great shape. Now we have concern of muscle wasting and he has been diagnosed with Parkinson’s but the Dr said he is too strong. Dat scan was abnormal thus the PD diagnosis. We have been told he can start on PD meds anytime he wants. Mentally he is declining and becoming weaker. We contour to research and found this Lymes disease dialogue associating the two. Neurologist wouldn’t even consider it and amid our questions turned to my husband and said ‘Do you have cancer?!’ We were shocked! His DO did further tests to rule out and we won’t go back to that Dr. so frustrating this journey we are on.

    1. Thanks for sharing your husband’s story. We know the Dat scan is abnormal in Parkinson’s disease but so much for other diseases. I typically look for treatable illnesses in patients with a chronic illness. I find patients in my practice who suffer from a chronic illness and Lyme disease. Call the office at 914 666 4665 if you have any questions.

    2. Did the doctors say he had STARI (southern tick associated rash illness) instead of Lyme? We are in a supposed Lyme free state and have had nearly identical path as you described. Now diagnosed with PD with DAT scan. All started not long after tick bite with bullseye rash.

  15. Hi Dr. Cameron,
    I recently had a fall, I’m 33 years old male. I hit my head and rolled my foot. I live in the Northwest Suburbs of Chicago. I went to the ER because I wasn’t able to put pressure on it and thought I had broken it again. They did a CT on my head, x-ray on foot and and back. Things came out fine except for my CT scan. The Dr. there came in and asked if I had ever had a stroke and I said no, she said what I have on my brain isn’t related to the fall and it’s old not new. I’m completely illiterate on matters concerning the areas of the brain. I also have symptoms concerning movement and somewhat uncoordinated; this is what the report says: Gray-white differentiation is grossly preserved. 9 mm x 6 mm focal hypodensity in the left basal ganglia region, probably dilated perivascular space in a patient this age, less likely chronic lacunar infarct. I went untreated with lyme and bartonella for 19 years, my first symptom that I developed was hand tremors, followed by sudden development of high BP, nevus of ota in my right eye, arrhythmia with tachycardia, panic attack/anxiety/agoraphobia, weird stretch marks that are all over my body, profuse sweating, and a multitude of other symptoms. I was treated Septemeber 2019 with Azithromycin for 1 month for bartonella(I beleive), and then a PICC line put in for 28 days of rocephin. I am not sure if I was correctly treated for bartonella or lyme. Is this normal for people with lyme to have that in there brain? Was treatment sufficient? The doctor I see in Elgin told me I have to wait a year to 18 months to see if things get better. I have an MRI scheduled next week. I appreciate your time, if you’d like to send me and email you should have access to see it otherwise I’ll check here.

    1. White spots can occur in many illnesses. I have patients in my practice with sweats that may suffer from Babesia. I find personalized treatment protocols helpful for patients. I also refer my patients to specialists to rule out other illnesses. Give my office a call at 914 666 4666 if you have any questions.

  16. Hello-
    Im 49 year old woman. Im otherwise very healthy and extremely physically active. I am a trained dancer. 3 years ago I began noticing tension in my right arm and hand. It was affecting my coordination and movement of my right arm. I would FEEL like my arm was doing a movement with 100% energy and length but videos showed otherwise. I have complete control over relaxing it. brushing my teeth and writing have been a chore and the tension is great. Again, I can relax it easily. 3 Neurologists have said my exam is totally normal and I dont present with typical Parkinsons but a DAT scan showed low dopamine levels and my Neuro at Yale said she thinks its Parkinsons or a rare brain disease. However they are stumped. Could it be co-infections/Lyme?
    Thank you so much

  17. I was diagnosed with spasmodic dysphonia and vocal tremor due to an issue with the basal ganglia . I have a history of Lyme disease several years ago. Unfortunately I am allergic to cephalosporins are there other options?

  18. Please Help! About 4 years ago (2016) I started noticing cognitive decline in my 51 year old husband. In 2018, his general practitioner did some blood tests which included “Lyme Ab IgG” and “Lyme Ab IgM” which both came back Negative. They also tested for Methylmalonic Acid, Vitamin B1, RPR, Ammonia, Lead, Arsenic, Mercury & Cadmium, which all came back normal. After much research, in February of 2019 @ 53 years old he was diagnosed via a DatScan with this “IMPRESSION: Decreased radiotracer binding in the basal ganglia consistent with Parkinson’s disease and/or dementia with Lewy body disease. ” 3 Neurologists have diagnosed my husband with Lewy Body Dementia, since, Cognitive Decline was his first symptom. He has very little movement disorders (some twitching, slow movement, scuffs feet walking, doesn’t swing arms walking, drooped eyelids, drooling, small handwriting, difficulty cutting meat, etc.). John’s Hopkins Neurologist diagnosed him with Atypical Parkinsonian Syndrome. In August of 2019 a PET Brain Scan indicated “Symmetric hypometabolism in bilateral frontal, temporal and parietal lobes”. Recently I was looking up “Hypometabolism” and found ““Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. LYME DISEASE appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism.”. This got me wondering about Lyme disease, even though he originally tested Negative in 2018, WHICH IS WHY I AM MESSAGING YOU. With all of this information, do you recommend another Lyme Disease blood test…and if so….please reply with the specific blood test for Lyme Disease (or any other test….based on my information). Please reply via Email….and THANKS (so much) IN ADVANCE FOR YOUR RESPONSE! Robin – Severna Park, MD

  19. I tested positive for 3 Lyme bands.
    I have severe tremor of left, and now
    on right side. I was treated with oral
    and IV anti-biotics. No tremor improvement after 6 months.

    What is the recommended lyme tremor treatment protocol ?
    Thanks

    1. I have patients where is unclear if Lyme disease and tick-borne illnesses are present. I arrange for consultations with other doctors to look for other illnesses. I have to comb over some patients to see if their are any treatment options.

  20. I had a basal ganglia infarct due most likely when I came off a 4 month round of antibiotic therapy, too soon, and was a month off of antibiotics. I had a three month headache that only subsided with steroid use. I had lost pituitary function due to Lyme beginning around 2006 after a tick bite. I was on hydrocortisone for panhypopituitarism-adrenal insufficiency-and developed a lung infection about Martin Luther King Day and went on to long acting steroids to treat the lung infection. I have a history of asthma beginning in childhood. Diagnosed by Elisa and Western blot at Stonybrook Labs as positive for Lyme 2010. Bit by a tick in 2006 in Portland, Oregon.

  21. I was diagnosed with unspecified Parkinsonism and my blood test revealed Lyme disease. I have tremors and a balance problem and a stumbling gait also
    my hands are limp and the right side of my body is rigid. Any recommendations Doc?

  22. I am a 62 yo female l discovered a bullseye type EM with central clearing, about 2 1/2 mos ago. I am testing negative (<.91) for IgG and IgM. I have the following symptoms: headaches, neck soreness, scalp tenderness, facial one side numbness and tingling, sore soles, swollen knee with painful joint, bad insomnia, tinnitus, neuropathy in extremities, difficulty multitasking and RLS. I also have involuntary body jerks sometimes as well. I have just finished 4 weeks of doxy and 2 weeks of Ceftin. The EM is still there and I basically feel bad. Any suggestions for what to do? Do you think that I have Lyme?? Thank you

  23. Dr. Daniel Cameron
    Jeannie Tyler

    I was diagnosed with Lyme disease once about 20 years ago and again, with another active infection about 5 years ago. The first time it took me 7 trips to my Dr’s office to get tested then I was put on doxycycline for a month. The second time I was tested for Lyme disease the first time I went to the Dr but it took 2 weeks to get the results back and I wasn’t started on antibiotics until the results came back. That time they only put me on doxycycline for 2-3 weeks. I started having tremors in my lower left abdomen a few years ago and now they are all over me. I am also very painful all over every day and I have severe insomnia and I also have to push harder than normal when I urinate. I was told this by my urologist a few months ago after testing. Is it still possible that Lyme disease could be affecting my brain and that’s what could be causing my other symptoms I described above? I’m going to see my regular Dr next month and will be asking her to refer me to a neurologist but I would like to hear your opinion so I can have something to back me up when I see the neurologist as I know how some Dr’s react towards Lyme disease in the first place.

    1. Neurologist typically focus on a broad range of illnesses. Some neurologists are reluctant to consider Lyme disease if the tests are negative, if 3 weeks of antibiotics have failed, or if their patient does not have a particular finding. I have seen individuals with unusual presentations thought to another illness.

      1. Dr. Daniel Cameron
        Barbara Lea Mitzner

        I had Parkinson’s
        Like symptoms
        Leg tremor. Moving internal tremors. Neurologist said probably PD. I started taking doxycycline from old Lyme diagnosis. All symptoms stopped. I believe this was Lymes recurring

  24. I have a “Supertentorial lesion” or written a different way by a different neurologist said it’s “1 or 2 non specific bright white spots in the white matter right centrum semiovale”. I just got a DATSCAN and the the radiologist said it’s abnormal. But my neurologist said the uptake is good and nothing to worry about. Could my abnormal DATSCAN be a result of Lyme and or these lesions? Thank you

  25. My brother has Parkinson’s. We grew up in a highly populated tick area. After an accident, having run through the mill of doctors and psychiatrists, having had Physical therapy for fifteen years, three doctors, during the same year, told me, his sister, to go out of the system and see a Lyme disease doctor. Over a two year period, and I can’t even begin to tell you how many antibiotics I’d been on, I got to the point that I could get off the sofa. I spoke with the Mayo, but they do not really back Chronic Lyme disease. Now, my brother is sick. His information is below. Are the statements included about Lyme disease correct or should he look at the possibility that Lyme disease has caused his problems.

    This is my brother’s note….

    A year or so ago I was tested for Lymes and it came back clean.

    I had a daT brain scan which showed both dopamine areas of my brain were low. That is a positive hit to identify Parkinson’s. This is a rare test. Most folks are not successful in trying to convince their doctors that such a test is useful to confirm Parkinson’s because they base their findings on numerous visual/physcial tests.

    Not only that but the medication works for me. It stops tremors. They say Lymes does not cause depletion of dopamine or cause most of the motor skills that Parkinson’s does. I also read that Parkinson’s medication does nothing to mask the symptoms of Lymes. So…in my case the meds are working, which proves Parkinson’s. My only hope is to be one of the very few lucky enough to get DBS (Deep Brain Stimulation) which will cancel most of the Parkinson’s effects.

    1. Lyme and Parkinson’s are both common. Some of my patients have had both. Ticks don’t care who they get a meal from. I have not tested my Lyme disease patients without Parkinson’s disease with a daT scan. I also have not treated my Lyme disease patients with Parkinson’s medication. I wish you well.

  26. My husband is 52. He began having movement & brain fog issues after COVID two years ago; particularly having issues on his left side & shuffling.
    His DAT was completed two days ago. He is now diagnosed with “Fairly advanced Parkinsonism”. We live in Arkansas. Myself and our oldest daughter have beth been treated for lyme from 2015-2020. My husband has refused to get tested for 10 years now. And his DAT scan reads: “Exam is abnormal. There is very little uptake seen on the right and what is seen in the right basal ganglia is confined to the caudate nucleus. There is activity seen on the left but it is confined to the basal ganglia and does not extend into the striata or putamen.”
    My question: Would finding a local doctor to prescribe the antibiotics still be worth a shot? I do not know what else we could afford at this time. He is our bread winner. Maybe a tele-appointment for advice.
    (Incidentally our oldest daughter has lyme borreliosis (AE) with epilepsy & autism and our other daughter has T1D.)

    1. I have had patients who have had a tick borne infection and Parkinson’s disease. I rely on the neurologist to manage their Parkinsonism. I found treatment for their tick borne illness helped their other symptoms. Call my office 914 666 4665 with your question.

Leave a Comment

Your email address will not be published. Required fields are marked *