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Syndrome of Transient Headache and Neurological Deficits with Cerebrospinal Fluid Lymphocytosis: Handl □ EDITORIAL □ Syndrome of Transient Headache and Neurological Deficits with Cerebrospinal Fluid Lymphocytosis: HaNDL Key words: pseudmigraine with lymphocytic pleocytosis, with negative aetiological results; (v) normal neuroradio- PMP, ICHD-II, FHM, CSF logical studies, except for transient, focal, decreased radio- nuclide uptake in brain SPECT; and (vi) non-permanent, focal non-epileptiform EEG changes. The duration of focal neurological deficits ranged from 5 minutes to 3 days Recently, reports of patients with syndrome of transient (mean±SD: 5±13 hours). The neurological manifestations headache and neurological deficits with cerebrospinal fluid were most commonly sensory symptoms (78% of episodes), lymphocytosis (HaNDL), previously termed pseudomigraine aphasia (60%), or motor deficits (56%). Visual symptoms, with lymphocytic pleocytosis (PMP), have been increasing which are common in migraine with aura, were not often ob- in number (1–5). However, due to the clinical similarities, served (12%). CSF lymphocytosis ranged from 10 to 760 other diagnoses such as familial hemiplegic migraine (mean±SD: 199±174) cells/ìl. Twenty-five percent of the pa- (FHM), neuroborreliosis, neurosyphilis, neurobrucellosis, tients had symptoms of a preceding viral-like illness, such as mycoplasma, meningitis, granulomatous and neoplastic general malaise with diarrhea, cough, and rhinitis. Gómez- arachnoiditis, encephalitis, and CNS vasculitis should be Aranda et al hypothesized that a viral infection could activate considered (6). the immune system, thereby producing antibodies that would In Japan, only two patients with HaNDL have been re- induce an aseptic inflammation of the leptomeningeal ported, one in 2002 (4) and the other in 2003 (5), suggesting vasculature (3). that the syndrome may in fact be underrecognized in Japan. In the 2nd Edition of the International Classification of In this issue, Tada et al (7) reported a patient exhibiting mi- Headache Disorders, (ICHD-II), HaNDL was defined and graine-like headache with amnesia and pleocytosis. classified in Group 7, “Headache attributed to non-vascular intracranial disorder” (6). The diagnostic criteria of HaNDL See also p 743. are as follows: A. episodes of moderate or severe headache lasting hours before resolving fully and fulfilling criteria C Memory disturbance in this patient continued for more and D; B. CSF pleocytosis with lymphocytic predominance than three weeks, although the duration of neurological defi- (>15 cells/µl) and normal neuroimaging, CSF culture and cits in HaNDL usually lasts less than three days (3). other tests for etiology; C. episodes of headache are accom- This syndrome was first described by Bartleson et al in panied by or shortly follow transient neurological deficits 1981 (1). They reported seven patients with migraine-like at- and commence in close temporal relation to the development tacks associated with cerebrospinal fluid (CSF) pleocytosis. of CSF pleocytosis; D. episodes of headache and neurologi- The episodic, severe headaches were preceded and accompa- cal deficits recur over <3 months (6). nied by sensory, motor, speech, and visual disturbances. Since FHM is characterized by migraine with aura includ- They postulated that the migrainous episodes were sympto- ing motor weakness, and can be associated with CSF matic of an underlying inflammatory disorder of the central pleocytosis, it should be differentiated from HaNDL (6). In nervous system. In 1995, Berg and Williams (2) reported FHM, chronic progressive cerebellar ataxia may occur inde- seven cases of HaNDL and conducted a literature review de- pendently of the migraine attacks. Disturbances of con- scribing 33 further patients. They speculated that HaNDL sciousness can occur, and FHM is very often mistaken for might be related to a single virus or to an idiosyncratic re- epilepsy (6). In Japan, it is possible that many cases of FHM sponse to a variety of viral agents. In 1997, Gómez-Aranda go undiagnosed. Chapman et al (8) examined the clinical et al (3) analyzed 50 patients with this syndrome and de- findings of 10 patients with HaNDL. They did not identify scribed the following clinical picture: (i) one or more epi- any mutations in the CACNA1A gene in eight of the HaNDL sodes of moderate-to-severe bilateral and/or hemicranial patients, and reported that this gene did not play a role in the headache accompanied by changing temporary neurological etiology of HaNDL, despite noting similarities between deficits, usually cheiro-oral numbness plus speech disorder, HaNDL and FHM, such as recurrent headache with reversi- and occasionally fever; (ii) total resolution of the recurrent ble neurologic deficits including motor weakness, and CSF episodes within 2 months; (iii) absence of symptoms and lymphocytic pleocytosis. signs between episodes; (iv) CSF lymphocytic pleocytosis Although the cause of HaNDL remains unclear, it seems 690 Internal Medicine Vol. 44, No. 7 (July 2005) that the syndrome is benign and rare. However, as the condi- report of 50 cases. Brain 120: 1105–1113, 1997. tion is likely to be underdiagnosed and/or misdiagnosed, this 4) Nomura T, Wakutani Y, Doi K, et al. A case of pseudomigraine with diagnosis should be considered when evaluating headache pleocytosis. Rinsho Shinkeigaku (Clin Neurol) (Tokyo) 42: 954–958, 2002 (in Japanese). with transient neurological features. 5) Tsukamoto T, Miyazawa K, Narikawa K, Irino S. A young woman with pseudomigraine with CSF pleocytosis. Clin Neurol (Tokyo) 43: Kenji NAKASHIMA,MD 12–15, 2003. Department of Neurology, Institute of Neurological Sciences, 6) Headache Classification Subcommittee of the International Headache Tottori University Faculty of Medicine, 683–8504 Society. The International Classification of Headache Disorders; 2nd Edition. Cephalalgia 24 (suppl 1): 1–160, 2004. References 7) Tada Y, Negoro K, Abe M, Ogasawara J, Kawai M, Mortimatsu M. A patient of migraine-like headache with amnesia, pleocytosis and tran- 1) Bartleson JD, Swanson JW, Whisnant JP. A migrainous syndrome with sient hyperfusion of cerebral blood flow. Intern Med 44: 743–746, cerebrospinal fluid pleocytosis. Neurology 31: 1257–1262, 1981. 2005. 2) Berg MJ, Williams JS. The transient syndrome of headache with neu- 8) Chapman KM, Szczygielski BI, Toth C, et al. Pseudomigraine with rology deficits and CSF lymphocytosis. Neurology 45: 1648–1654, lymphocytic pleocytosis: A calcium channelopathy? Clinical descrip- 1995. tion of 10 cases and genetic analysis of the familial hemiplegic mi- 3) Gómez-Aranda F, Cañadillas F, Martí-Massó JF, et al. Pseudomigraine graine gene CACNA1A. Headache 43: 892–895, 2003. with temporary neurological symptoms and lymphocytic pleocytosis. A Internal Medicine Vol. 44, No. 7 (July 2005) 691.
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