Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (Handl Syndrome): A case report

The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity. This disease has been related with migrainous headaches. It is a benign disorder, self-limited, and characterized by fluctuating neurological symptoms and cerebrospinal fluid (CSF) lymphocytosis. A small proportion of patients develop intracranial hypertension as a consequence of the illness. Confusional state may be also observed. We describe a case of a 29 years old man with acute onset of headache, dysthermia sensation, vomits, aphasia, and difficulty to perform daily activities such as unlocking the mobile phone. Blood tests as well as computed tomography (CT) and magnetic resonance imaging (MRI) were normal. Cerebroespinal fluid analysis revealed a lymphocytic pleocytosis (47 cells/μl, 100% lymphocytes). Electroencephalogram showed moderate slow rhythm in the left hemisphere, with frontotemporal predominance, and without epileptiform activity. With the diagnosis of HaNDL syndrome the patient was accepted in the Department of Neurology and discharged asymptomatic without treatment. Correspondence to: Eduardo Esteban Zubero, Emergency Department of Hospital San Pedro-26006, Logroño, Spain, Tel: +34654123994; Email: eezubero@gmail.com


Introduction
The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity [1]. The first description of this disease in the literature was provided in 1981 [2]. The International Headache Society sets forth specific diagnostic criteria that define this syndrome (Table 1) [3].
HaNDL is most frequently observed during the third and fourth decades of life, with no consistent gender predominance identified [4][5][6]. The etiopathogenesis of HaNDL is poorly understood. Some patients report a preceding non-specific viral prodromal illness [6], but studies have failed to provide a definite viral association [2,3].
Neurologic deficits typically last 15-120 minutes, although a range of 5 minutes to 3 days has been reported. While approximately 75% of HaNDL cases have a monophasic course, repeated attacks that occur for weeks or even months following the initial attack have been reported. When repeated attacks are observed, neurological deficits may vary due to the involve of different brain regions [2,3,5].
Herein, we describe a case of HaNDL syndromewith a short review of the literature of this illnes and cases reported.

Case report
A previously healthy 29-year-old man with no prior significant medical history was admitted in our Emergency Department reporting acute onset of headache with associated nausea, vomiting, dysthermia sensation, aphasia, and difficulty to perform daily activities such as unlocking the mobile phone. Neurological exploration revealed repetitive language and aphasia without disturbs of cranial nerves. Sensitivity and strenght were symmetrical were preserved. Bilateral flexor cutaneous-plantar réflex as well as visual field test were normal. Any signs of meningism were observed.
During his admission, a blood test was performed revealing only discrete leukocytosis with left deviation (13.3 x 1000/μL with 75.5% neutrophilia). Computed tomography (CT) scan and magnetic resonance imaging (MRI) did not show any disturbs ( Figure 1). Electroencephalogram (EEG) showed moderate slow rhythm in the left hemisphere, with frontotemporal predominance, and without epileptiform activity. A lumbar puncture was performed to complete the study. Cerebroespinal fluid (CSF) analysis revealed a lymphocytic pleocytosis (47 cells/µl, 100% lymphocytes).
With the diagnosis of HaNDL syndrome the patient was accepted in the Department of Neurology. During his admission, the patient progressed favorably recovering the neurological functionality completely without any specifical treatment. The patient was discharged after 7 days.

Discussion
The syndrome of headache with neurologic déficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity comprising sudden onset migrainous headaches (generally in headache-naïve individuals) accompanied by a constellation of fluctuating neurological symptoms and CSF lymphocytosis. Neurological symptoms include hemiparesis and hemisensory deficits (which often migrate in a fashion consistent with a cortical spreading depression), aphasia (HANDL favours the left hemisphere), nausea, vomiting, visual disturbance (including decreased vision, homonymous hemianopsia, and photopsia/photophobia), and less commonly, acute confusional state [9,10], elevated intracranial pressure (ICP) and papilledema [1], and cerebral herniation [8], which worsen de prognosis.
The headache, observed frequently after the neurological symptomatology, may be hemicranial or holocranial, pulsatile, and moderate-severe intensity. Its duration is variable, although it is usual to self-limit in few hours [11]. Neurologic deficits typically last 15-120 minutes, although a range of 5 minutes to 3 days has been reported. While approximately 75% of HaNDL cases have a monophasic course, repeated attacks that occur for weeks or even months following the initial attack have been reported. When repeated attacks are observed, neurological deficits may vary due to the involve of different brain regions [2,3,5].
HaNDL is most frequently observed during the third and fourth decades of life, with no consistent gender predominance identified [3,5,6]. However, some case reports are observed in adolescents and childhood [12,13]. The etiopathogenesis of HaNDL is poorly understood. Some patients report a preceding non-specific viral prodromal illness [6,14], but studies have failed to provide a definite viral association [2,3]. The presence of antibodies directed against the CACNA1H subunit of the T-type voltage-gated calcium channel in one small study supported the inflammatory or autoimmune hypothesis [15]. Cortical spreading depression-associated cerebral oligaemia has been observed during HaNDL attack, and may play a significant role [8,16].
Diagnosis of HaNDL syndrome is confirmed after having ruled out other diseases of the central nervous system according to the diagnostic criteria showed in Table 1. CSF pressure and protein are generally elevated at the time of diagnosis, and neuroimaging is usually normal. EEG during the acute symptoms may show slowed rhythm, like our case [11,14]. Some authors suggested to perform a CT angiography in patients affected of HaNDL syndrome, neuroimaging tests normal, and suspected diagnosis of vasculitis [8,11,16].
Prognosis of these patients is benign and medical treatment is only necessary to control headache. However, when ICP and papilledema are observed, CSF drainage and acetazolamide trearment are recquired [8,9,17].
In conclussion, HaNDL, a rare disease with diverse clinical manifestations, remains a diagnosis of exclusion. It may be explained on the basis of migrainous or post-viral/inflammatory pathophysiology. The prognosis of this illness is benign and the treatment is symptomatic. However, symptoms including elevated IPC, papilledema and brain herniation may be observed, recquering urgent treatment. We describe a HaNDL case trying to improve the knowledge of this pathology.

Conflicts of interest
No conflict of interest shown in the realization of this writing.

Funding
No external funding sources and any comments are received.