Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL)
- Christine L Lay, MD, FRCPC
Christine L Lay, MD, FRCPC
- Associate Professor
- Women's College Hospital
- Christina Sun-Edelstein, MD
Christina Sun-Edelstein, MD
- Department of Clinical Neurosciences
- St. Vincent's Hospital
INTRODUCTION AND DEFINITION
The syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a self-limited, benign entity that was first clearly characterized in 1981 , when it was called a migrainous syndrome with cerebrospinal fluid (CSF) pleocytosis. It was given its current name in 1995 , and has also been referred to as pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis (PMP syndrome) . As the name implies, HaNDL is characterized by one or more episodes of severe headache, transient neurologic deficits, and lymphocytic pleocytosis in the CSF.
The precise etiology of HaNDL is not yet fully understood. Though some initially speculated that the syndrome represented a severe migraine [4,5], others favored an inflammatory or infectious origin, given the CSF lymphocytosis, frequent viral prodrome, and monophasic course [1,2]. However, despite extensive viral serological evaluation, there are only few reports suggesting a viral association, including isolated cases linked to echovirus 30 , human herpesvirus 6 infection , and human herpesvirus 7 infection .
Findings on single-photon emission computed tomography (SPECT), perfusion imaging with CT and MRI, transcranial Doppler, and electrophysiology studies of patients with HaNDL are suggestive of a migrainous pathophysiology:
●SPECT studies have demonstrated focal or widespread areas of decreased blood flow on the side of origin of the neurologic deficits [9-12], suggestive of the spreading depression-like mechanism similar to that proposed for migraine.
●Head CT perfusion imaging and MRI perfusion techniques in several studies have demonstrated global hemispheric or focal regions of hypoperfusion correlating with neurologic deficits [13-17]. In one case report, a follow-up CT perfusion study 36 hours after resolution of the patient's neurological deficits showed full reversal of this hypoperfusion, supporting cortical spreading depression as an important mechanism in the pathophysiology of HaNDL .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Bartleson JD, Swanson JW, Whisnant JP. A migrainous syndrome with cerebrospinal fluid pleocytosis. Neurology 1981; 31:1257.
- Berg MJ, Williams LS. The transient syndrome of headache with neurologic deficits and CSF lymphocytosis. Neurology 1995; 45:1648.
- Morrison DG, Phuah HK, Reddy AT, et al. Ophthalmologic involvement in the syndrome of headache, neurologic deficits, and cerebrospinal fluid lymphocytosis. Ophthalmology 2003; 110:115.
- Day TJ, Knezevic W. Cerebrospinal-fluid abnormalities associated with migraine. Med J Aust 1984; 141:459.
- Walter CT, Grogan WA. Migraine with tardy pleocytosis. Neurology 1986; 36:733.
- Castels-van Daele M, Standaert L, Boel M, et al. Basilar migraine and viral meningitis. Lancet 1981; 1:1366.
- Emond H, Schnorf H, Poloni C, et al. Syndrome of transient headache and neurological deficits with CSF lymphocytosis (HaNDL) associated with recent human herpesvirus-6 infection. Cephalalgia 2009; 29:487.
- Stelten BM, Venhovens J, van der Velden LB, et al. Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL): A case report with serial electroencephalography (EEG) recordings.. Is there an association with human herpes virus type 7 (HHV-7) infection? Cephalalgia 2015.
- Gómez-Aranda F, Cañadillas F, Martí-Massó JF, et al. Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis. A report of 50 cases. Brain 1997; 120 ( Pt 7):1105.
- Caminero AB, Pareja JA, Arpa J, et al. Migrainous syndrome with CSF pleocytosis. SPECT findings. Headache 1997; 37:511.
- Fuentes B, Diez-Tejedor E, Frank A. Syndrome of headache with neurological deficits and CSF lymphocytosis: a spreading depression mechanism? The role of SPECT. Headache 1998; 38:324.
- Fuentes B, Diez Tejedor E, Pascual J, et al. Cerebral blood flow changes in pseudomigraine with pleocytosis analyzed by single photon emission computed tomography. A spreading depression mechanism? Cephalalgia 1998; 18:570.
- Pettersen JA, Aviv RI, Black SE, et al. Global hemispheric CT hypoperfusion may differentiate headache with associated neurological deficits and lymphocytosis from acute stroke. Stroke 2008; 39:492.
- Yilmaz A, Kaleagasi H, Dogu O, et al. Abnormal MRI in a patient with 'headache with neurological deficits and CSF lymphocytosis (HaNDL)'. Cephalalgia 2010; 30:615.
- Babi MA, Applebee A, Shapiro R, Waheed W. Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis presenting as acute neurological emergencies. Cephalalgia 2017; 37:284.
- Burke MJ, Lamb MJ, Hohol M, Lay C. Unique CT Perfusion Imaging in a Case of HaNDL: New Insight into HaNDL Pathophysiology and Vasomotor Principles of Cortical Spreading Depression. Headache 2017; 57:129.
- Guillan M, DeFelipe-Mimbrera A, Alonso-Canovas A, et al. The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis mimicking an acute stroke. Eur J Neurol 2016; 23:1235.
- Kappler J, Mohr S, Steinmetz H. Cerebral vasomotor changes in the transient syndrome of headache with neurologic deficits and CSF lymphocytosis (HaNDL). Headache 1997; 37:516.
- Thie A, Fuhlendorf A, Spitzer K, Kunze K. Transcranial Doppler evaluation of common and classic migraine. Part II. Ultrasonic features during attacks. Headache 1990; 30:209.
- Totaro R, De Matteis G, Marini C, Prencipe M. Cerebral blood flow in migraine with aura: a transcranial Doppler sonography study. Headache 1992; 32:446.
- Fumal A, Vandenheede M, Coppola G, et al. The syndrome of transient headache with neurological deficits and CSF lymphocytosis (HaNDL): electrophysiological findings suggesting a migrainous pathophysiology. Cephalalgia 2005; 25:754.
- Pascual J, Valle N. Pseudomigraine with lymphocytic pleocytosis. Curr Pain Headache Rep 2003; 7:224.
- Erdağ E, Çelebisoy N, Yüceyar AN, et al. Antibodies to DNA repair proteins in headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) patients. Acta Neurol Belg 2015; 115:137.
- Chapman KM, Szczygielski BI, Toth C, et al. Pseudomigraine with lymphocytic pleocytosis: a calcium channelopathy? Clinical description of 10 cases and genetic analysis of the familial hemiplegic migraine gene CACNA1A. Headache 2003; 43:892.
- Kürtüncü M, Kaya D, Zuliani L, et al. CACNA1H antibodies associated with headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL). Cephalalgia 2013; 33:123.
- Filina T, Feja KN, Tolan RW Jr. An adolescent with pseudomigraine, transient headache, neurological deficits, and lymphocytic pleocytosis (HaNDL Syndrome): case report and review of the literature. Clin Pediatr (Phila) 2013; 52:496.
- Parissis D, Ioannidis P, Balamoutsos G, Karacostas D. Confusional state in the syndrome of HaNDL. Headache 2011; 51:1285.
- Giorgetti A, Mariani G, Patruno GM, Romorini A. The transient syndrome of headache with neurological deficits, cerebrospinal fluid pleocytosis and acute confusional state: a case report. J Headache Pain 2005; 6:476.
- Mateo I, Pinedo A, Gómez-Beldarrain M, García-Moncó JC. [Acute confusional state secondary to transient headache and neurological deficits with cerebrospinal fluid lymphocytosis]. Neurologia 2004; 19:763.
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33:629.
- Finke C, Mengel A, Prüss H, et al. Anti-NMDAR encephalitis mimicking HaNDL syndrome. Cephalalgia 2014; 34:1012.
- Toth CC. Persistent cerebrospinal fluid abnormalities in the syndrome of headache, neurological deficit, and cerebrospinal fluid lymphocytosis despite resolution of clinical symptomatology. Headache 2002; 42:1038.
- Gonçalves D, Meireles J, Rocha R, et al. Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL): a pediatric case report. J Child Neurol 2013; 28:1661.
- Barón J, Mulero P, Pedraza MI, et al. HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases. Neurologia 2016; 31:305.