Headache associated with neurologic deficits and CSF lymphocytosis

Simy Parikh MD (Dr. Parikh of The Jefferson Headache Center at Thomas Jefferson University has no relevant financial relationships to disclose.)
John G Burkett MD (

Dr. Burkett of The Jefferson Headache Center at Thomas Jefferson University has no relevant financial relationships to disclose.

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 June 20, 2019; expires June 20, 2022

This article includes discussion of headache associated with neurologic deficits and CSF lymphocytosis, syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis, transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis, HaNDL, migrainous syndrome with cerebrospinal fluid pleocytosis, 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) presents as new, transient headache with focal neurologic symptoms and lymphocytic pleocytosis on cerebrospinal fluid analysis. It is a rare, self-limiting condition. Because this condition is a frequent mimicker of acute stroke, awareness of HaNDL could expedite diagnosis and avoid unnecessary and potentially harmful interventions. In this article, the authors provide updates on the clinical manifestations of HaNDL, diagnostic criteria and findings, and disease management.

Key points


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


• Headache is migraine-like, but most patients do not report a prior history of migraine. The pain may be accompanied by nausea, vomiting, photophobia, or phonophobia. Sensory deficits are the most common accompanying transient neurologic deficits, followed by aphasia, motor deficits, and visual disturbances.


• Accompanying features of HaNDL can include preceding viral syndrome, increased intracranial pressure, focal EEG abnormalities, and elevated CSF protein. A case study showed increased neurofilament light chain levels, suggestive of acute axonal injury.


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


• The etiology of HaNDL is debated, and it is not known if HaNDL has a single specific cause.


• HaNDL does not have a specific neuroimaging correlate. Ictal brain imaging may show delayed brain perfusion and narrowing of cerebral arteries.


• Symptoms typically resolve within 3 weeks but can last up to 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 CSF pressure and pleocytosis. Each episode would last up to several days and resolve without sequela. Similar cases were subsequently reported, but it was not until 1981 that Bartleson and colleagues coined the term “migrainous syndrome with cerebrospinal fluid pleocytosis” after characterizing 7 patients over 6 years with similar findings and finding 2 similar cases from other case studies of patients with migraine and abnormal CSF findings (Bartleson et al 1981). The authors described a series of patients who had 3 to 12 episodes of migraine-like attacks accompanied by sensory, motor, speech, and visual disturbances in addition to cerebrospinal fluid abnormalities. The condition spontaneously resolved in all patients within 1 to 12 weeks.

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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