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Paper text:
leptospirosis commonly presents as an acute illness occurring in a biphasic pattern of fever followed by an afebrile period and again fever with organ involvement .
neurological involvement ( neuroleptospirosis ) is rare . among the several manifestations of neural involvement ,
myeloradiculopathy , myelopathy , cerebellar dysfunction , transverse myelitis , guillain - barre syndrome , optic neuritis , peripheral neuropathyhave also been described .
the hitherto undescribed entity of bilateral abducent nerve palsy as a manifestation of neuroleptospirosis is reported herewith .
a 22-year - old male agricultural worker presented with fever , nausea , abdominal pain , yellowish discoloration of the eyes and myalgia .
he had noticed the symptoms seven days prior to admission and had been treated symptomatically at a local dispensary .
he denied a history of alcohol usage . since this was during a time when our hospital was getting numerous cases of leptospirosis , and in view of his occupation , a possible clinical diagnosis of leptospirosis
injection crystalline penicillin two million units intravenously sixth hourly was commenced while awaiting lab reports for malaria parasite and leptospira , dengue , viral hepatitis serology .
urea 28 mg / dl , serum creatinine 1.4 mg / dl and rbs 112 mg / dl .
chest x - ray was normal . on the second night of hospitalization during routine rounds at 8.30 pm ,
the patient replied in the affirmative when asked about diplopia , but did not have any pain or headache .
the diplopia was worse when he directed his gaze to the left or right ( figure 2 , diplopia chart ) .
onset was rapid since evaluation a few hours earlier had not shown any neurological deficit . limitations of eye movements were confined to abduction in both eyes ( figure 3 ) .
the size of the convergent squint or esotropia was larger on distant fixation than on near fixation .
cerebrospinal fluid ( csf ) analysis showed 16 leukocytes / mm - all lymphocytes , glucose of 59 mg / dl and protein level of 39 mg / dl .
diplopia chart depicts that diplopia was worse when gaze was directed to the left or right
. shows extra - ocular movements ; it can be seen from this chart that the limitations of eye movements were confined to abduction in both the eyes .
titer was 50 u / ml ( < 15 u / ml negative , 15 - 20 intermediate , > 20 positive ) confirming the clinical diagnosis .
he also showed complete recovery from abducent palsy over the next five days and was discharged on the eleventh day after admission .
it is an important cause of acute febrile illness in china , the indian subcontinent , southeast asia , africa , south america and central america where malaria , typhoid and dengue are also common .
human infection occurs by direct contact with urine or blood of an infected rodent or animal , or from water or soil contaminated by urine . the organisms can penetrate abraded skin or intact mucous membrane , and enter the circulation and rapidly disseminate to various tissues .
the infection is commonly seen in farmers , sewage workers , veterinarians , and animal handlers . after an incubation period of 7 - 14 days
the first phase , leptospiremic or septicemic phase , has an abrupt onset , lasts for a week and is characterized by fever , chills , headache , skin rash , myalgia and conjunctival suffusion . the second phase or the immune phase , which can last up to 30 days , is characterized by leptospiruria and the development of anti - leptospira antibodies .
. additional involvement of pulmonary , renal , cardiovascular , and neurological systems can occur . in this phase
the rarer clinical presentations described in literature are myeloradiculopathy , myelopathy , cerebellar dysfunction , transverse myelitis , cerebrovascular accident , cerebral venous thrombosis , cerebral arteritis , subarachnoid haemorrhage , optic neuritis , mononeuritis multiplex , peripheral nerve palsy , psychosis , suicidal behaviour , encephalitis , and cerebellitis .
transient paraparesis has been described in a recent report by lih - shinn et al .
although implicated in various neurological manifestations , leptospirosis is often overlooked by clinicians in the evaluation of febrile illnesses with neurological manifestations . in the case
reported by kavitha and shastry , their patient had fever , jaundice and lower limb weakness , urinary retention and decreased sensory perceptions below t4 level . as in our case , the confirmation of the diagnosis was by positive anti - leptospira igm serology . in the report by costa et al . , facial palsy was observed following an illness consistent with leptospirosis and in their case , microscopic agglutination test ( mat)- the confirmatory test was not done , but seroconversion was observed in the macroagglutination test . in the report by mumford et al . , flaccid paraplegia was observed .
in contrast to our patient , this case ended with fatality ascribable to renal and hepatic involvement .
the sixth cranial nerve ( abducens nerve ) innervates the lateral rectus muscle in the ipsilateral eye .
paralyses can be due to direct damage of the sixth cranial nerve , encephalon nuclei or less frequently , diffuse axonal damage .
bilateral sixth nerve palsy is a rare clinical condition . unlike unilateral palsy , which is often due to local causes such as trauma , increased intracranial pressure , brain stem glioblastoma etc .
, the bilateral form is due to systemic causes such as vasculopathy secondary to atherosclerosis and immune mediated vasculitis .
patients with bilateral sixth nerve palsies complain about binocular horizontal diplopia being worse in the gaze direction of the paretic lateral rectus muscle .
currently , there is paucity of knowledge regarding the pathogenetic pathways involved in the above neurological manifestations
. the molecular mechanisms by which spirochetes interact with cellular barriers and the chain of events involved in leptospira meningitis and other leptospirosis - related neurological phenomena remain unknown . after invading the bloodstream
, leptospira plays a role in the activation of innate immunity cells , such as macrophages , via interaction among the transmembrane toll - like receptor 2 ( tlr2 ) , cd14 , and leptospiral lipopolysaccharide .
the organisms migrate from the bloodstream to the csf by crossing the blood brain barrier .
the ensuing neurological disease is dependent on the virulence of strains and on the development of an inflammatory response . yet , interestingly , most of the current animal models for the spirochetoses do not recreate the manifestations of the neurological spectrum .
experimental approaches to the human neurological manifestations of the spirochetoses have shown inability and difficulty in reproducing aspects of the human disease in animal models .
though reports of other cranial nerve palsies in leptospirosis are made in literature , abducent paralysis has not been mentioned hitherto . in our patient , typical clinical presentation of leptospirosis
the other causes of abducent palsy were excluded by medical history and by other investigations .
it is also to be noted that the patient developed abducent palsy approximately on the ninth day of symptomatic disease , when the clinical manifestations attributed to leptospirosis had subsided .
this is consistent with the concept that cranial palsies , including the present bilateral abducent palsy in patients with leptospirosis is mediated by immunological mechanisms .
the novelty of this case is that whereas numerous case reports exist of other cranial nerve palsies occurring in leptospirosis , the present case is probably the first one that exemplifies abducent nerve palsy developing as a result of antecedent leptospira infection .
the present case report has highlighted the hitherto unreported manifestation of bilateral abducent nerve palsy .
neuroleptospirosis should be considered in the differential diagnosis of all neuroinfections especially in endemic areas .
practicing physicians in developing countries , where advanced diagnostic facilities are not available , should be aware of the different patterns of clinical presentation and the various rarer manifestations of leptospirosis to be able to make a clinical diagnosis even when confronted with the unusual associations of leptospirosis .
leptospirosis , a disease of great significance in tropical countries , presents commonly as a biphasic illness with acute febrile episode in the first phase followed by a brief afebrile period and then by the second phase of fever with or without jaundice and renal failure . 
 however , it has varied manifestations and unusual clinical features ascribed to immunological phenomena can occur due to the additional involvement of pulmonary , cardiovascular , and neurological systems . among the various neurological features , 
 aseptic meningitis is the most common myeloradiculopathy , myelopathy , cerebellar dysfunction , transverse myelitis , guillain - barre syndrome , optic neuritis , peripheral neuropathy hare also described . 
 cranial neuropathy involving facial nerve is a rare , but known neurological manifestation . 
 sixth nerve palsy in neuroleptospirosis has so far not been reported . 
 we hereby present the occurrence of bilateral abducent nerve palsy in a patient with leptospirosis .