Central Nervous System Vasculitis Due to an Endemic Zoonosis in Turkey; Tularemia

Abstract

Tularemia is a bacterial zoonotic disease. The etiologic agent is francisella tularensis which is a gram negative coccobacillus. It is also an epidemic disease in some parts of Turkey. Clinical forms are ulceroglandular or glandular, oculoglandular, oropharyngeal, respiratory, and typhoidal forms. Neurological involvement is rare. It is usually presented with meningitis and encephalitis in literature.

Our 42-year-old patient was suspected for demyelinating disease, ischemic cerebrovascular disease and vasculitis because of acute onset of neurological symptoms. She was diagnosed as tularemia during the investigation of her lymphadenitis. No etiologic risk factor was found for cerebrovascular disease, and demyelinating disease was excluded. Digital substraction angiography revealed the narrowing of the cerebral vessels. The lesions were partially regressed with the treatment. However, a new infarction developed with the interruption of treatment. All these findings suggested the diagnosis of central nervous system vasculitis due to francisella tularensis infection.

Our case was important as it was the first vasculitic case due to tularemia in the literature.

INTRODUCTION

Tularemia is a zoonotic disease caused by an intracellular, gram-negative facultative bacteria called Francisella tularensis. The bacteria effects at least 250 species including human beings. It is especially seen in North pole, and mostly in Scandinavia, North America and Eurasia. It has been known in Turkey since 1956 and it has been seen widely in Turkey since the epidemic in Marmara region in 1988 (1).

Tularemia presents with various clinical illnesses depending on its exposure to the body. After 3-5 days of an incubation period, the patient experiences sudden flu-like disease, fever, chills, generalized aches, headache and weakness. Erythema nodosum, erythema multiforme,maculopapular rash, acne and vesicular lesions are seen in 20 % of patients. Meningitis, abscess and endocarditis are fulminant signs of tularemia and the neurological involvement of the disease is rare.

In this study we aimed to emphasize a case diagnosed as a central nervous system vasculitis caused by tularemia which is an epidemic zoonosis of our country with a rare neurological involvement.

CASE

42 year old previously healthy woman presented to the neurology emergency department with diplopia, nausea, vomiting. She had internuclear ophtalmoplegia, left hemiparesis and left hemihypoestesis in her neurological examination. A pontine infarction was detected in diffusion weighted magnetic resonance imaging (MRI) (Figure I). There were hyperintense non-contrast enchancing lesions in bilateral periventricular, peritrigonal, pericallosal regions, centrum semiovale and corona radiata on T2 and FLAIR sequences of cranial MRI in as well as pons. Our initial diagnosis were demyelinating disease, ischemic cerebrovascular disease and vasculitis.

Figure 1.

An acute pontine infarction.

Her cervical and cranial MRI angiography, electrocardiography, transthoracic echocardiography, cervical and thoracal MRIs, visually evoked potentials (VEP) were normal. In her routine blood tests there was a mild leucocytosis (10.53 m/L), C reactive protein was 5.75 mg/L, and sedimentation rate was 64 mm/h. Lumbar puncture, oligoclonal band, IgG index, vasculitic and young stroke markers were in normal limits. Digital substraction angiography revealed narrowings and irregulatories of bilateral medial and anterior cerebral arteries diagnosing vasculitis (Figure 2-3).

Figure 2.

Narrowings and Irregulatories of bilateral median and anterior cerebral arteries on angiography.

Figure 3.

Narrowings and Irregulatories of bilateral median and anterior cerebral arteries on angiography.

She experienced a cervical lymphadenopathy during her follow up. There were two irregular shaped lymphadenopathies sizing 11.6*19.7 mm and 8.3*17.4 mm on her neck ultrasound. Her neck MRI revealed contrast enhancing lymphadenopathies with inflammatory findings and cystic cavitation in right parotid gland leading the diagnosis of suppurative lenphadenitis. As the lymphadenopathies did not regress after antibiotherapy, small needle aspiration biopsy was performed. A necrotising granulomatous infection was detected. After an etiological workup; Francisella tularensis microagglutination test was 1/160 positive. She was living in a rural area and in a recent time 40 cases had been diagnosed as tularemia.

Her repeated cerebropsinal liquid samples were normal. The patient was given streptomycin and doxycycline for 3 weeks. 25 days after her discharge, a new lesion was detected near right lateral ventricule (Figure 4). She had discontinued her antibiotherapy for 5 days. Antibiotherapy started again. Old lesions were partly regressed on her cranial MRI (Figure 5).

Figure 4.

A new lession on right hemisphere near lateral ventricule.

Figure 5.

Regression of old lesions on left figure.

DISCUSSION

Francisella tularensis, a gram negative coccobacillus is the agent of tularemia. It is transmitted to humans by direct contact with infected animals especially by rabbits, by ingestion with contaminated water, meat and by inhalation. There has been no reported cases of human to human transmission. In Turkey it is mostly transmitted by contamined water (3,4).

The signs of the disease varies according to the bacteria’s virulance. The incubation period is usually 3-5 days. As the agent reaches the lymph nodes, it forms several granulomas and causes suppurative lymphadenopathies. It causes a typical abscess formation. The disease spreads from lymph nodes to the lymphatic system, lung, liver, spleen, kidneys and central nervous system (5,6).

Tularemia presents with 6 clinical illnesses; ulceroglandular, oculoglandular,oropharyngeal, pneumonic and typhoidal. In humans, ulceroglandular tularemia is the most common form of the disease. In Turkey oropharyngeal type is mostly seen with tonsillopharengitis and enlargement of cervical lymph nodes (7). We also examined enlargement of cervical lymphadenopathies in our patient without fever and weakness.

Central nervous system involvement is rare in tularemia. It is thought to be the reason of untreated bacteremia spreading to meninges. Cases of meningitis and encephalitis were reported in literature (8). After 3-30 days of the first signs of the disease, meningitis or encephalitis can be seen. Confusion, headache, meningeal irritation signs and fever can be observed in patients. Also seizure was reported in literature. Mononuclear monocytosis, various protein and glucose levels were observed in cerebrospinal fluid and gram stain is frequently negative (9). There is no reported case about central nervous system vasculitis due to tularemia, that’s why our case was thought to be important.

Our patient was initially diagnosed as demyelinating disease as she experienced sudden internuclear ophthalmoparesis and left sided hemiparesis. But MRI lesions were not contrast enchancing, oligoclonal bands and IgG index were normal, there were no spinal lesions and VEP was normal. There was also no risk factor for ischemic cerebrovascular disease. Vasculitic markers were in the normal range but DSA showed vasculitic signs.

It has been known that meningovascular syphilis, tuberculosis meningitis, fungal meningoencephalitis, neurosistisercosis, varicella zoster encephalitis, HIV and herpes viruses can cause stroke effecting cerebral vessels. Inflammation is caused by vascular and perivascular lymphositic infiltration of parenchymal and leptomeningeal vessels. It causes narrowings and irregularity of middle and small sized leptomeningeal vessels. Some vessels can be occluded by organised thrombus (10,11). Syphilis, tuberculosis, herpes infection, HIV and HCV infections were excluded by serology in our patient. It’s known that tularemia is a suppurative necrotising granulomatous infection. Cervical lymphadenopathy, high acute phase reactants, and biopsy detecting the agent supported the diagnosis. As the lesions regressed after antibiotherapy, and the new lesions appeared after untreated therapy interval and DSA findings also supported CNV vasculitis.

As a conclusion, CNS vasculitis due to an infection must be in mind in cases with cervical lymphadenopathy and neurological findings especially in unknown etiology. Diagnostic tests according to systemic examination can help to diagnose the rare etiologies.

Tularemia rarely causes neurological signs and it is endemic in our country. Being aware of the endemic diseases in country can lead us in diagnosing rare but treatable diseases.