“The cooperation of the ophthalmologists, neurologists and neurosurgeons is the only way to solve the complex cases none could approach separately.”

MD. Tatiana Roşca

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Special medical article:
Controverses in neuroborreliosis clinical experience and not only
by Dr. Tatiana Roşca

Borreliosis or Lyme disease

Borreliosis or Lyme disease is caused by the spirochetes Borrelia burgdorferi and is an infection transmitted by the bite of infected ticks. Fig.1;
Borrelia burgdorferi include: Borrelia afzelii and Borrelia garinii (specific to Europe). The tick is ixodes ricinus urbane. Fig.2;


Clinical manifestations of Lyme disease: [1]:


Phase 1 : it is situated at the site where the tick bites the skin and has the aspect of erythema chronicum migrans. The rash begins after 3-30 days from the bite of the infected tick. 18% of the patients do not present the rash. Fig.3;


Phase 2 : appears in weeks or months. The patients develop neurological (15%), heart (5%), or arthritic (60%) manifestations. Untreated , weeks to months after the bacterium drilled into the body the joints, heart and nervous systems will be affected. The spirochetes adhere promptly and penetrate the endothelial cells and other types of cells as the glial ones with mediated attach through the exposure surface. Fig.4;


Phase 3 : cronic neurological syndromes and arthritic manifestations. Affects HEART: abnormal heart rhythm and heart failure and both CENTRAL AND PERIPHERIC NERVOUS SYSTEM JOINTS SYSTEM. Fig.5;



Differential diagnosis of the rheumatologist: [2]:

  • Aseptic meningitis
  • Fibromyalgia
  • Reactive arthritis
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus


Other Problems to Be Considered

  • AV nodal block
  • Encephalitis
  • Radiculopathy


Differential diagnosis of the neurologist [3]:

  • Acute Disseminated Encephalomyelitis
  • Multiple Scletosis
  • Alzheimer Disease
  • Persistent Idiopathic Facial Pain
  • Ankylosing Spondylitis
  • Prion-Related Diseases
  • Fibromuscular Dysplasia
  • Aseptic Meningitis
  • Toxic Neuropathy
  • Bell Palsy
  • Trigeminal Neuralgia
  • Confusional States and Acute Memory Disorders
  • Viral Meningitis


Other Problems to Be Considered

  • Atypical facial pain
  • Babesiosis
  • Bacterial meningitis
  • Chronic fatigue syndrome
  • Dementia
  • Depression
  • Gout or pseudogout
  • Human granulocytic anaplasmosis (previously termed ehrlichiosis)
  • Infectious mononucleosis
  • Mononeuropathy multiplex
  • Plant dermatitis
  • Radiculopathy
  • Reiter syndrome
  • Rheumatoid arthritis
  • Rocky Mountain spotted fever


Differential diagnosis of the ophthalmologist [4]:

  • Abducens Nerve Palsy
  • Ocular Manifestations of Syphilis
  • Trochlear Nerve Palsy
  • Oculomotor Nerve Palsy
  • ARMD, Nonexudative
  • Optic Neuritis, Adult
  • Bell Palsy
  • Optic Neuritis, Childhood
  • Branch Retinal Artery Occlusion
  • Papilledema
  • Branch Retinal Vein Occlusion
  • Rocky Mountain Spotted Fever
  • Conjunctivitis, Viral
  • Sarcoidosis
  • Diplopia
  • Scleritis
  • Endophthalmitis, Bacterial
  • Sudden Visual Loss
  • Episcleritis
  • Synechia Peripheeral Anterior
  • Extraocular Muscles, Actions
  • Herpes Simplex
  • Tuberculosis
  • Herpes Zoster
  • Uveitis, Anterior, Childhood
  • Horner Syndrome
  • Uveitis, Anterior, Granulomatous
  • Keratitis, Herpes Simplex
  • Uveitis, Anterior, Nongranulomatous
  • Keratitis Interstitial
  • Uveitis, Classification
  • Neovascularization, Corneal, CL-related
  • Uveitis, Intermediate
  • Nonpseudophakic Cystoid Macular Edema
  • Uveitis, Juvenile Idiopathic Arthritis


Other Problems to Be Considered

  • Macular edema
  • Orbital myositis
  • Orbital pseudotumor



Clinical manifestations - more frequent are dermatological, neurological, ophthalmological, heart, rheumatic and psychiatric.


As Lyme disease is multisystemic, differential diagnosis includes:

  1. Viral infections
  2. Aseptic Meningitis
  3. Disseminated  gonococcic  infection
  4. Tertiary syphilis
  5. Multiple Sclerosis
  6. Guillain-Barre Syndrome
  8. Systemic Lupus Erythematosus
  9. Subacute Bacterial Endocarditis
  10. Thyroiditis
  11. Reiter Syndrome
  12. Chronic Fatigue Syndrome
  13. Psychic disordeers



Figures - Slideshow

Note: click on the links in the page: Fig.A, to see the whole image.

1st case

Female patient , 57 y.o, urban, teacher

  • Istoric:
    Presented in August 2007 in the Neurology Department, diagnosed with:
    • Periventricular lacunar strokes
    • Cerebral small-vessel disease
    • Chronic disharmonic vestibular syndrome (possible bilateral peripheric affection )
    • Arterial hypertension
    • High triglycerides
    Fig.6; Fig.7; Fig.8; Fig.9;
  • Clinic differential diagnosis:
    - Brain demyelination
    - Post traumatic brain and cervico-thoracic spinal cord sequelae
    - Otological disorders
    - Ocular disorders
    - Neuropathy and radiculopathy by ischemia
    - Antiphospholipid syndrome


The only place in the human body where the aspect of the blood vessels can be seen live is the retina ophthalmoscopic exam.


The suggestive aspect of FO for the presence of the antiphospholipid antibodies (due to an infection) was the one that induced the necessity of confirming immunologic investigation followed by etiologic research of the antiphospholipid syndrome (APS).


APS is a prethrombotic state that, early discovered can prevent the thrombotic state. Bacterial wall contains phospholipids that call for B2GPI, forming together an autoimmune antibody with a role in pushing the bacteria off the blood flow favouring the prethrombotic state.


This theoretical assess presumes the existence of a phospholipid on the bacterium surface which will attach to B2GP1 thus determining the thrombus. [5]


Fig.33; Fig.34;


Some of the antiphospholipidic antibodies react with the apoptotic cells that have suffered a modification of their normal distribution, accompanied by the asymetry of the membranar phospholipids and the exposure of the anionic phospholipids on the cell surface. [6]


Apoptotic cells induce appearance of anti-phospholipid autoantibodies. [7]


Binding of Anti-phospholipid autoantibodies to apoptotic cells depends on ß2-glycoprotein. [8].


  • Spirochetes and their excretion substances act directly on glial cells, neurons and Schwann cells which explains the brain aspect of MRI (demyelinating lesion ).
  • The mechanism of direct action both of anticardiolipin antibodies and of spirochets add up at the level of vessels endothelium.
  • Immunological factors, including the production of proinflammatory cytokines and the formation of immune complexes, and also genetic factors, such as human leukocyte antigen (HLA)–DR4 and HLA-DR2 are present in the articular liquid. [9]


2nd case

Patient C.I., 35 y.o., urban environment

  • History:
    • 14th March 2003 - falls on stairs injuring her thoraco- lumbar-sacral area;
    • 27th March 2003 - presents paresthesias in the left hemilimba, left palm, left fingers.
    • 1st April 2003 - unsteady on her left foot.
    • May 2003 - thyroid echography
    • July 2003 - paresthesias only in the left fingers.
    • August 2003 - neurologic exam: radicular lesion C6-C8
    • September 2003 - temporary decrease in bilateral hearing and menstrual cycle disorders;
    • 10th October 2003 - sudden decrease VA in OS >OD, 3 ophthalmologic exams and cerebral MRI;
    • APP: - 2 spontaneous abortions (at 6 weeks of pregnancy)
    • AV: - 2cpp
    • FO normal
    • Bilateral left inferior quadranopsia = lesions at the level of optic radiations (bilateral temporal , parietal and occipital lesions)
  • Fig.35; Fig.36; Fig.37; Fig.38; Fig.39; Fig.40; Fig.41; Fig.42;



  • Clinic differential diagnosis:
    - Brain demielynation
    - Post traumatic brain and cervico-thoracic spinal cord
    - Otological disorders
    - Ocular disorders
    - Neuropathy and radiculopathy by ischemia
    - Menstrual cycle disorders and spontaneous abortions
    - Antiphospholipid syndrome
  • Secondary Antiphospholipid Syndrome:
    - Infectious process: viral, bacterial, parasitary
    - Autoimmune pathology: - colagenous disease - immunodefficiency syndrome
    - Haematological pathology
    - Paraneoplastic syndrome
  • Treatment suggestion:
    VIRCHOW’s TRIAD (1854) in infection:
    Hipercoagulability + endothelial lesion + venous stasis

    ETIOLOGY: treatment targeted to infection
    EFFECT: blood hiperviscosity
    RECOVERY: according to possibilities... suggested: Hyperbaric oxygenotherapy in a hyperbaric chamber



3th case

Student, 14 y.o., urban environment

  • APP:
    - at 4 – acute laringitis hospitalized 24 hours on bronhovaxom until 12 y.o.
    - at 6 - casual headache treated with nurofen, increased between 13 – 14 y.o.
  • History:
    - April 2009 (14 y.o.) owl scratch,
    3 days after - fever, shivering – nurofen, oscilloccocinum
    7 days after - swelling and pains at the level of the right submandibulary salivary gland
  • Consultatii:
    - BMF (privat, facultate)
    - ORL
    - Paraclinic: hemoleucograma normala, probele inflamatorii negative, imunologia pentru boli autoimune negative, probe toxicologice la IML negative
    - Institutul Cantacuzino: imunologie pentru paraziti =negativ pentru bacterii = negativ pentru virusi= negativ Rickettsia =slab pozitiv IgG

  • Evolution:
    12th May 2009
    : muscular contraction and desynchronization of movements → Neurology Paraclinical = normal EMG = normal → Child Neuropsychiatry

    On her mother’s account she is taken to the hospital for infectious diseases where she is suspicioned of (“the disease of swelling heads”) :
    - it can be treated by octagam 1g/kg body, rocephine 1g/24 hours, albendazol, dexamethasone 24 mg/day, vitaminotherapy (6 days);
    - at sortie she gets doxiciclinum 200mg/day ( 5 days) 100mg/day (5 more days)

    During admission there appear :
    • atrocious pains at the level of the tibio-tarsis articulations, café au lait spots and nodules of 0,5/1cm concomitently with pain disappearence
    • perfalgan 2 flc/day and lyrica
    • bilateral pains at the sacro-illiac joints level, pains at the lumbar vertebral canal, hyperestezia and local heat
    • sleep apnea (Class IV NYHA), arrhythmias (cardiomyopathy)
    19th May 2009 : Diagnosis at sortie: PSEUDONEUROLOGICAL SYMPTOMS. ANXIETY SYMPOM under observation Neuropsychiatry consultation

    24th May 2009 : rehospitalization in the infectious diseases hospital and sortie in a “wheeling chair” diagnosed with seronegative polyarthritis

    25th May 2009 : suspicion of debut of ankylosing spondylitis (HLA B27 negative) or polyrheumatoid arthritis (seronegative feritin ) Treatment with methylprednisolonum and salazopirina

    Investigating on at mother’s suggestion for suspicioned Guillain Barre syndrome.
    EMG: sensitive polyneuropathy suggesting an infectious cause

    3th June 2009 : The 3rd hospitalization in another infectious diseases hospital: dg. Borrelia with investigations:

    • IMR brain, cervical and thorax spine = normal
    • IMR lumbo-sacral spine = chronic inflammatory process at the sacro-illiac joints level (bilaterally)
    • CT-scan for thorax = normal,
    • LP = normal

Only one tonic-clonic seizure for 30 minutes keeping conscience – desitin. Consultation at 7 neuropsychiatrists and one neurosurgeon

 Treatment with :

    • 4g/24 ROCEPHINE for 28 days + OCTAGAM
    • 2g/kg body + ACYCLOVIR 4g/day for21 days


Clinical signs and symptoms:

    • sleep and behaviour disorders, hyperacusis
    • acrodermatitis (treates with desloratadinum)
    • head cyanosis for seconds (10-14 times a day during the first week of treatment) alternating with palor
    • falling hair
    • asthenia, night sweating
    • synovitis at knees level
    • pains in cervical spine
    • modifications of taste and smell perception, stomach pains
    • transitory diplopia



Home treatment at Dr. B.P.Bozsik indications . Fig.46; Fig.47;
At the end of the treatment Fig.48; Fig.49; Fig.50;




Peculiarities of the case:
Extremely diverse progress of the disease symptoms :

NEUROLOGY : headache

INFECTIOUS: fever, shivering

BMF : right salivary submandibular gland implication

GASTRO-ENTEROLOGY: abdominal pains

CARDIOLOGY: sleep apnea (Class IV NYHA), arrhythmias (cardiomyopathy)

RHEUMATOLOGY : Seronegative polyarthritis - bilateral pains at the sacro-illiac joints level, - pains at the lumbar vertebral canal.

OPHTHALMOLOGY: transitory diplopia

DERMATOLOGY: skin lession suggesting a “spirochete”

NEUROLOGY : Investigating on at mother’s suggestion for suspicioned Guillain Barre syndrome + EMG: sensitive polyneuropathy suggesting an infectious cause
↓↓ ↓
BUDAPEST – DR. B.P. Bozsik



Diagnosing borreliosis means an exclusion diagnosis
being a lot more difficult than one can imagine.



[1] Lyme Disease - Author: Gerald W Zaidman, MD, Professor of Clinical Ophthalmology, New York Medical College; Chief of Cornea Service, Acting Director, Department of Ophthalmology, Westchester Medical Center Updated: Jul 25, 2008

[2] John O Meyerhoff, MD, Assistant Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine; Clinical Scholar in Rheumatology, Department of Medicine, Sinai Hospital of Baltimore, Updated: Jul 24, 2009

[3] Augusto A Miravalle, MD, Fellow, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School Coauthor(s): R Philip Kinkel, MD, FAAN, Associate Professor of Neurology, Harvard Medical School; Director, Multiple Sclerosis Center, Beth Israel Deaconess Medical Center; Consultant Neurologist, Children's Hospital of Boston Updated: Jul 23, 2009

[4] Gerald W Zaidman, MD, Professor of Clinical Ophthalmology, New York Medical College; Chief of Cornea Service, Acting Director, Department of Ophthalmology, Westchester Medical Center Updated: Jul 25, 2008

[5] Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000;15:145-51

[6] Price BE, Rauch J, Shia MA, et al. Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a ß2-glycoprotein I-dependent manner. J Immunol 1996;157:2201-8

[7] Levine JS, Subang R, Koh JS, Rauch J. Induction of anti-phospholipid autoantibodies by beta2-glycoprotein I bound to apoptotic thymocytes. J Autoimmun 1998;11:413-24[erratum, J Autoimmun 1999;12:143.

[8] Price BE, Rauch J, Shia MA, et al. Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a ß2-glycoprotein I-dependent manner. J Immunol 1996;157:2201-8.

[9] E-Medicine: Lyme Disease John O Meyerhoff, MDJohn O Meyerhoff, 2009


Last update: 13.01.2017