Headache with Neurologic Deficits and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a self-limiting syndrome characterized by moderate to severe headache associated with focal neurological deficits such as, motor or sensory deficits, or speech disturbances, occurring in the context of lymphocytosis in the cerebrospinal fluid. Due to being a rare condition, data regarding HaNDL is sparse. Therefore, we conducted this review to analyze data related to 93 patients of HaNDL, to characterize their demographics, wide range of presenting symptoms, treatment options in the acute and chronic phases, EEG, brain imaging and CSF findings.

We performed a systematic review of cases reported through PubMed and Google scholar database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol.  

The mean age was 28.8 years at onset. 70 patients (75.2%) were adults, while 23 (24.7%) were pediatrics. 30% of patients experienced relapsing episodes of HaNDL symptoms. The most common type of headache reported was unilateral severe throbbing episodic headache. Other associated symptoms included sensory deficit (60%) and motor deficits (54.8%). The least common symptoms were nystagmus and agraphia. Antiviral agents were a common treatment option in the acute phase [n=23 patients (23.6%)], while Flunarizine was the most commonly used agent in the chronic setting [n= 3 patients (3.2%)]. The most common brain MRI findings included nonspecific white matter lesions and meningeal enhancement, whereas the most common EEG findings include diffuse and focal slowing. The mean CSF opening pressure was 240.5 mmH2O. CSF protein was elevated in 59 patients , with a mean value of 114mg/dL.

HaNDL tends to affect young individuals with a slight male predominance. Unilateral severe throbbing episodic headache with associated hemi-paresthesia and hemiparesis were the most common presenting symptoms based on our review. Early recognition of this syndrome is critical in order to prevent unnecessary treatments such as, antimicrobials.