Headache associated with neurologic deficits and CSF lymphocytosis

Julio Pascual MD (Dr. Pascual of University Hospital Marqués de Valdecilla and IDIVAL in Santander, Spain, received honorariums for serving on the advisory boards of Allergan and Amgen-Novartis.)
Stephen D Silberstein MD, editor. (

Dr. Silberstein, Director of the Jefferson Headache Center at Thomas Jefferson University, receives honorariums from Allergan, Avanir Pharmaceuticals, Curelator, Depomed, Dr. Reddy's Laboratories, eNeura,  INSYS Therapeutics, Lilly USA, Supernus Pharmacerticals,  Thernica and Trigemina for consulting. He is also the  principal investigator for a clinical trials conducted by Alder Biopharmaceuticals, Amgen, electroCore Medical, Lily USA and Teva.

Originally released May 5, 1999; last updated August 21, 2017; expires August 21, 2020

This article includes discussion of headache associated with neurologic deficits and CSF lymphocytosis, HaNDL, and pseudomigraine with temporary neurologic symptoms. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Headache associated with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), also known as pseudomigraine with pleocytosis, is a benign but spectacular syndrome, thought to be of autoimmune etiology, combining headache, focal neurologic symptoms, and lymphocytic pleocytosis, usually in young to middle-aged men. In this article the author reviews the history and clinical manifestations, including new diagnostic criteria, neuroimaging findings, and practical management of this condition, which is one of the most frequent stroke mimics.

Key points


• Headache associated with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a self-limited syndrome that is characterized by a sudden onset of headache with temporary neurologic deficit and CSF lymphocytosis.


• Headache may be bilateral or hemicranial. It lasts an average of 19 hours, and it may be accompanied by nausea, vomiting, photophobia, or phonophobia, but most patients do not report a history of migraine headaches.


• Sensory symptoms, language disorders, and hemicorporeal weakness lasting a mean of 5 hours are the more frequent focal deficits.


• The diagnosis of HaNDL is made after excluding more common conditions that present with headache and transient neurologic signs and symptoms.


• HaNDL is 1 of the most frequent stroke mimics treated with thrombolysis.


• All reported patients with HaNDL recovered completely without treatment by 3 months.

Historical note and terminology

In 1951 Symonds described a man who had stereotyped spells of visual loss and unilateral weakness that were followed by headache, drowsiness, and vomiting (Symonds 1951). Associated with these symptoms were increased cerebrospinal fluid pressure and pleocytosis. Each episode would last up to several days and resolve without a sequel. Similar cases were subsequently reported, but it was not until 1981 that Bartleson and colleagues coined the term “migrainous syndrome with cerebrospinal fluid pleocytosis” (Bartleson et al 1981). The authors described a series of patients who had a limited number of migraine-like attacks accompanied by sensory, motor, speech, and visual disturbances in addition to cerebrospinal fluid abnormalities, and they provided a literature review of similar cases. In 1995, after reviewing the available case reports and adding 7 patients with similar presentation, Berg and Williams proposed the term “headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL)” (Berg and Williams 1995). Finally, Gomez-Aranda and colleagues described a series of 50 patients with this syndrome and called it “pseudomigraine with temporary neurological symptoms” (Gomez-Aranda et al 1997). The exciting history of this condition, including the early description of Spanish cases, has been reviewed (Martin-Balbuena and Arpa-Guitierrez 2007; Marti-Masso 2008).

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