Neurol Sci
DOI 10.1007/s10072-016-2585-y

LETTER TO THE EDITOR

Headache with transient neurological deficit: a case report
with hemispheric hypoperfusion and without lymphocytosis
Elena Martı́nez Velasco1
Angel Luis Guerrero1

•

Patricia Mulero1 • Marı́a Pedraza1 • Ana I. Calleja1 •

Received: 10 February 2016 / Accepted: 15 April 2016
Ó Springer-Verlag Italia 2016

Dear Editor,
Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is an uncommon
disorder described in 1981 by Bartleson et al. Current
diagnostic criteria (ICHD-III beta version 7.3.5) consider
episodes of moderate or severe headache, lasting hours and
associating cerebrospinal fluid (CSF) pleocytosis with
lymphocytic predominance [1]. Neuroimaging studies and
CSF culture are required to be normal.
Neurological deficits [2] more commonly reported are
sensory symptoms (78 % of cases), aphasia (66 %), and
motor weakness (41 %). In addition to these symptoms,
other features as elevation of CSF proteins [2] have also
been described.
To draw attention to this potentially misdiagnosed disorder, our aim is to report a case of headache and transient
neurological deficits with a severe cerebral perfusion disturbance and the absence of CSF lymphocytosis.
A 15-year-old male with a prior history of migraine was
admitted to emergency department due to a non-fluent
aphasia and sensory and motor deficit in right limbs of
40 min of evolution. He described a severe stabbing
headache starting in right fronto-parietal scalp associating
phonophobia and photophobia. A cerebral unenhanced and
perfusion computed tomography (CT) was performed,
while headache and a mild sensory disturbance in his right
limbs were still present. Unenhanced CT was normal, but
perfusion CT revealed an increased mean transit time
(MTT) and a diminished cerebral blood flow (CBF)
& Elena Martı́nez Velasco
emartinezvelasco@gmail.com
1

Neurology Department, University Hospital, Avda. Ramón y
Cajal, 3, 47005 Valladolid, Spain

throughout the entire left cerebral hemisphere not confined
to a particular vascular territory (Fig. 1). Cerebral blood
volume (CBV) was normal. Findings were consistent with
hypoperfusion throughout all left cerebral hemisphere.
Neurological deficits lasted less than 1 h. A diffusionweighted brain magnetic resonance imaging (DWI-MRI)
was performed within 24 h from clinical onset with no
restricted diffusion lesions and with normal signal intensity
of the brain parenchyma. An ultra-early carotid ultrasound
imaging and transcranial Duplex showed a generalized
increase in distal vascular resistance and segmental accelerations in both middle cerebral arteries with the absence of
arterial occlusion. The angiography TC showed no alterations. The existence of a complete hemispheric perfusion/
diffusion mismatch, together with the clinical course
including the presence of headache, led to a presumed
diagnosis of a syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis
(HaNDL), so a lumbar puncture was performed 3 days
after admission without pleocytosis or hyperproteinorrachia. A new CT perfusion 5 days after clinical onset
showed normal cerebral flow with normal CBV, MTT, and
CBF in left cerebral hemisphere. Carotid ultrasound
imaging and transcranial Duplex study was repeated with
normalization of distal resistance and flow accelerations.
Cerebral SPECT 10 days after clinical onset showed areas
of decreased radionuclide uptake suggesting decreased
blood flow in left temporal–parietal region (Fig. 2).
CSF microbiological studies and extensive immunological determinations were negative. The patient suffered
no new episodes and neurological exam was normal at
hospital discharge. Control cerebral SPECT was repeated
2 months later with blood flow normalization (Fig. 2b).
The presentation of sudden-onset neurological deficits at
emergency department always leads neurologist to be

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Fig. 1 Perfusion computed tomography at emergency department revealed an increased MTT (a) and a diminished CBF (b) with normal CBV
(c) throughout the entire left cerebral hemisphere

Fig. 2 First cerebral SPECT during acute phase a showed areas of decreased blood flow in the left temporal–parietal region. Two months after
clinical onset a new cerebral SPECT, b showed blood flow normalization

aware of the possibility of a stroke. Entities such as
HaNDL should be considered in the differential diagnosis
of stroke particularly in young patients [3]. Existence of
hypoperfusion in the entire left cerebral hemisphere in an
area not restricted to a vascular territory, and the absence of
a lesion restricted in DWI with a complete perfusion/diffusion mismatch rule out an acute stroke [4]. This pattern
in a whole hemisphere with patterns of benign oligemia
rather than ischemia has been previously described during
a HaNDL attack [4, 5].

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Pathophysiology of HaNDL remains unknown. It has
been suggested a vascular disorder mediated by an
inflammation in the meningeal vascular system, resembling
cortical spreading depression-like mechanism similar to
that proposed for migraine with aura. Reversible hypoperfusion observed in our case in cerebral CT perfusion, and
brain SPECT could support this vascular theory.
Cerebrospinal fluid lymphocytosis is a consistent finding
in the literature, and therefore, it was included among
HaNDL diagnostic criteria [1]. In spite of the absence of

Neurol Sci

lymphocytosis in our patient, clinical characteristics as
well as CT perfusion and SPECT reversible changes support, in our opinion, the diagnosis of this syndrome. The
absence of pleocytosis in our patient could be explained by
a delay in performing lumbar puncture; nevertheless, in the
same way that SPECT or electroencephalographic
anomalies may be absent in this syndrome, we can
hypothesize that there might be an HaNDL variant with
vascular involvement and no CSF inflammation.
In conclusion, in this case, as shown in previous reports
[5], we have observed cerebral hypoperfusion during the
acute state of an incomplete form of HaNDL, a rare but
probably under-recognized syndrome. This information
and the possible absence of lymphocytosis might be considered in the future revision of ICHD. Our description
shows the important role that advanced imaging techniques, as CT perfusion, can play in ruling out an acute
stroke, and ng unnecessary and non-innocuous therapies as
endovenous thrombolysis.

References
1. Headache Classification Subcommittee of the International Headache Society (2013) The International Classification of Headache
Disorders: 3rd edition (beta version). Cephalalgia 33(9):629–808
2. Gómez-Aranda F, Cañadillas F, Martı́-Massó JF et al (1997)
Pseudomigraine with temporary neurological symptoms and
lymphocytic pleocytosis. A report of 50 cases. Brain
120:1105–1113
3. Krause T, Nolte CH (2012) The syndrome of transient headache
and neurological deficits with cerebrospinal fluid lymphocytosis
(HaNDL) as an acute ischemic stroke mimic leading to systemic
thrombolysis: a case report. Clin Neurol Neurosurg 114:689–690
4. Pettersen JA, Aviv RI, Black SE, Fox AJ, Lim A, Murray BJ
(2008) Global hemispheric CT hypoperfusion may differentiate
headache with associated neurological deficits and lymphocytosis
from acute stroke. Stroke 39:492–493
5. Barragán NG, Guillán M, Zarza B et al (2012) Focal CT
hypoperfusion in HaNDL. J Neurol 259:1755–1757

Compliance with ethical standards
Conflict of interest None.

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