Neuroleptospirosis emerges as a distinct but often missed leptospirosis phenotype in French Guiana
Leptospirosis already carries a wide clinical range, from self-limited febrile illness to fulminant multiorgan disease. In French Guiana, neurological involvement has been harder to define, in part because no consensus diagnostic framework has existed and because meningitic or encephalitic symptoms can be attributed to other tropical infections, metabolic illness, or severe systemic sepsis. A multicenter retrospective study spanning 2015 to 2021 now places neuroleptospirosis on firmer clinical ground by separating patients with objective neurologic involvement from those with non-neurologic leptospirosis.
Among 146 patients with laboratory-confirmed or probable leptospirosis, 18 met criteria for neuroleptospirosis, representing 12% of the cohort. The mean annual incidence was 0.88 cases per 100,000 inhabitants, with a 95% CI of 0.52 to 1.39. In a region where leptospirosis is already a public health concern, that rate signals a neurologic complication that is uncommon at the population level but far from rare in clinical practice. The syndrome concentrated in younger patients and often presented with cerebrospinal fluid abnormalities rather than dramatic focal deficits, a pattern that can easily be missed unless clinicians actively look for it.
Meningeal presentations dominated, while encephalitis remained uncommon
The neurologic phenotype was not diffuse or uniform. Most cases were meningeal, accounting for 14 of 18 patients, or 78%. Three patients had an encephalitic presentation and one had meningoencephalitis. Those proportions matter at the bedside because meningeal symptoms may prompt lumbar puncture, while altered mental status alone may trigger broader infectious or neurologic workups without leptospirosis immediately rising to the top of the differential.
Cerebrospinal fluid examination was not performed systematically, which reflects real-world care rather than ideal study conditions. Lumbar puncture occurred in 28 of 146 patients, or 19%. Among those sampled, pleocytosis appeared in 18 of 28, or 64%. The median CSF leukocyte count reached 42 cells/mm3, with an interquartile range of 13 to 240 cells/mm3. Lymphocytic predominance was present in 8 of 13 differential counts, or 62%, and CSF protein was only mildly elevated, with a median of 0.51 g/L and an interquartile range of 0.32 to 0.88. Hypoglycorrhachia was absent. This pattern points to inflammatory meningeal disease without the low glucose that often pushes bacterial meningitis higher on the list.
The biologic signal is consistent with an infection that can inflame the leptomeninges without producing the purulent CSF profile clinicians expect in classic bacterial disease. Mild protein elevation and lymphocyte-skewed pleocytosis fit a syndrome in which immune activation, endothelial injury, and direct or indirect pathogen effects may converge in the central nervous system. One patient had cerebral infarction on MRI, and another had pachymeningitis. Those imaging findings were uncommon, but they reinforce that the neurologic spectrum extends beyond uncomplicated meningitis.
Younger age and the absence of inflammatory laboratory markers tracked with neurologic involvement
Age under 30 years was associated with neuroleptospirosis, with an odds ratio of 5.56 and a 95% CI of 1.72 to 18. The same was true for the absence of leukocytosis during hospitalization, with an odds ratio of 3.29 and a 95% CI of 1.04 to 10.39, and the absence of thrombocytopenia, with an odds ratio of 4.46 and a 95% CI of 1.39 to 14.32. Those associations are clinically interesting because they run counter to the instinct that more systemic inflammatory derangement should always accompany more severe organ involvement.
A younger patient with fever, headache, meningeal signs, and limited hematologic disruption may not appear to be the sickest person in the ward. Yet that profile, in this cohort, mapped onto neurologic leptospirosis more often than the classic picture of high leukocyte counts and thrombocytopenia. The finding suggests that neuroleptospirosis may at times emerge in patients whose systemic disease seems less dramatic, even while the central nervous system is already involved. In practical terms, the absence of thrombocytopenia or leukocytosis should not reassure clinicians out of considering the diagnosis when neurologic symptoms are present.
Favorable outcomes did not mean the syndrome was trivial
Cases classified as neuroleptospirosis had favorable outcomes under the study definition. The odds of sepsis were lower, with an odds ratio of 0.28 and a 95% CI of 0.10 to 0.79. No intensive care unit admissions and no deaths were recorded among the neuroleptospirosis group. That is an important clinical counterweight to the usual fear that central nervous system involvement necessarily predicts catastrophic infection.
Still, favorable survival should not be mistaken for diagnostic simplicity. The lack of ICU admission and death may reflect the specific case mix captured by the diagnostic criteria, the timing of hospital presentation, or the tendency for neurologic disease to be recognized before irreversible systemic deterioration. It may also reflect the broader biology of leptospiral nervous system involvement, which can generate striking neurologic symptoms without the same degree of hemodynamic collapse seen in severe pulmonary or renal disease. In other words, the syndrome can be dramatic without being uniformly fatal.
A retrospective design leaves the biggest unanswered question at the diagnostic threshold
This study strengthens the case for treating neuroleptospirosis as a real and definable clinical entity in endemic tropical settings. It also exposes the limits of current practice. Lumbar puncture was performed in fewer than one in five patients overall, which means neurologic involvement could have been underdetected. Brain MRI was obtained in only 8 patients with neuroleptospirosis, limiting any attempt to map imaging patterns with confidence. The retrospective design also makes it impossible to know how many cases might have been missed because symptoms were subtle, transient, or overshadowed by systemic illness.
The authors’ definition required neurological symptoms plus objective CSF and/or neuroimaging abnormalities. That approach gives the entity clinical rigor, but it also narrows case capture to patients who were investigated thoroughly enough to meet the threshold. Future prospective work will need systematic CSF analysis and microbiological testing to resolve how often leptospira truly invades the central nervous system, which clinical clues should prompt invasive testing, and whether distinct pathophysiologic subtypes exist across meningitic, encephalitic, and meningoencephalitic presentations.
French Guiana offers a useful setting for that work because leptospirosis is endemic and clinicians are already managing a broad infectious differential. The next challenge is not proving that neurologic leptospirosis exists. It is deciding how early to suspect it, how aggressively to investigate it, and which laboratory or imaging markers should move a patient from presumed systemic leptospirosis to a targeted neuroinfectious workup.