7.3.5 Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL)

Previously used terms:
Migraine with cerebrospinal pleocytosis; pseudomigraine with lymphocytic pleocytosis.

Description:
Migraine-like headache episodes (typically one to twelve) accompanied by neurological deficits including hemiparaesthesia, hemiparesis and/or dysphasia, but positive visual symptoms only uncommonly, lasting several hours. There is lymphocytic pleocytosis. The disorder resolves spontaneously within three months.

Diagnostic criteria:
A. Episodes of migraine-like headache fulfilling criteria B and C
B. Both of the following:

    1. accompanied or shortly preceded by the onset of at least one of the following transient neurological deficits lasting >4 hr

      a) hemiparaesthesia
      b) dysphasia
      c) hemiparesis

    2. associated with CSF lymphocytic pleocytosis (>15 white cells per µl), with negative aetiological studies

C. Evidence of causation demonstrated by either or both of the following:

    1. headache and transient neurological deficits have developed or significantly worsened in temporal relation to the CSF lymphocytic pleocytosis, or led to its discovery
    2. headache and transient neurological deficits have significantly improved in parallel with improvement in the CSF lymphocytic pleocytosis

D. Not better accounted for by another ICHD-3 diagnosis.

Comments:
The clinical picture of 7.3.5 Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) is of 1-12 discrete episodes of transient neurological deficits accompanied or followed by moderate to severe headache. Most of the episodes last hours, but some may last for more than 24 hours. The neurological manifestations include sensory symptoms in about three quarters of cases, aphasia in two thirds and motor deficits in a little over half. Migraine-aura-like visual symptoms are relatively uncommon (fewer than 20% of cases). The syndrome resolves within three months.

In addition to CSF lymphocytosis (up to 760 cells/µl), there are elevations of CSF total protein (up to 250 mg/dl) in >90% of cases and of CSF pressure (up to 400 mm CSF) in more than 50% of cases. The presence of a viral prodrome in at least one quarter of cases has raised the possibility of an autoimmune pathogenesis of 7.3.5 Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL). A recent description of antibodies to a subunit of the T-type voltage-gated calcium channel CACNA1H in the sera of two patients with this disorder supports this view.

Papilloedema is occasionally present. Routine CT and MRI scans (with or without intravenous contrast) and angiography are invariably normal when performed outside of an episode. Ictal brain imaging may show delayed brain perfusion without increased diffusion-weighted imaging changes, and narrowing of cerebral arteries. Also, grey matter oedema and sulcal enhancement have been described in a single patient. Microbiological studies have been uniformly normal. EEG and SPECT scans may show focally abnormal areas consistent with the focal neurological deficits.

Most patients with this syndrome have no prior history of migraine. The clinician must consider other diagnoses that may share some of its clinical features, including 1.2.3 Hemiplegic migraine (although mutations of the CACNA1A gene, the cause of 1.2.3.1.1 Familial hemiplegic migraine type 1 (FHM1), have been excluded in several patients with 7.3.5 Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL)), neuroborreliosis, neurosyphilis, neurobrucellosis, mycoplasma, granulomatous and neoplastic arachnoiditis, encephalitis and CNS vasculitis.