In this case of a young female presenting with headache and transient neurologic deficits with cerebrospinal fluid (CSF) lymphocytosis, we attempted to exclude other possible underlying etiologies. Although HaNDL is a self-limiting condition, it is part of a large differential diagnosis. Complicated or hemiplegic migraine, aseptic meningitis, meningoencephalitis, and stroke are among many conditions that could mimic this syndrome. Exclusion of infectious causes and acute cerebrovascular insult such as ischemic stroke is essential for diagnosing HaNDL syndrome. Stroke in young remains a very important condition that must be excluded because of the limited time window for thrombolysis. Diffusion-weighted MRI is highly accurate in acute ischemic stroke of less than 6 h duration and recommended when differentiating stroke from HaNDL [5].
Hemiplegic migraine is clearly different from HaNDL. Hemiplegic migraine starts before the patient is 20 years old and is often associated with a family history of hemiplegic migraine or migraine. A constant feature of HaNDL is the CSF lymphocytic pleocytosis. CSF pleocytosis of more than 10 to 15 mononuclear cells/mm3 does not occur in migraine [6]. Interestingly, unlike migraine, HaNDL has a slight predilection for males [7]. Moreover, most patients do not have a previous history of migrainous headaches. HaNDL also is separated easily from the autosomal dominant syndrome of recurrent migraine coma with focal cerebral oedema, CSF pleocytosis, and progressive cerebellar ataxia [8].
Despite thorough evaluation for infectious etiologies of HaNDL in both children and adults, its possible infectious origin has not been yet identified [9]. However, there are reports of cases whose CSF analysis showed a positive PCR for human herpesvirus type 7 (HHV-7) [10] and human herpesvirus-6 infection [11]. This suggests a possible role of a viral infection in the etiology of HaNDL which is mostly immune related. There are many infectious conditions that can present with neurological deficits, headache, and CSF pleocytosis, but the transient nature of the deficits and lack of consistently discoverable etiology despite extensive evaluations typify HaNDL. Recurrent pleocytosis raises the diagnostic possibility of HSV (Mollaret’s) meningitis, which presents with episodic mild fever, photophobia, headache, and change in mental status [12]. Characteristic CSF findings include marked pleocytosis with neutrophils, lymphocytes, and large mononuclear (Mollaret) cells that are typical for this disease, but not for HaNDL.
It was proposed that HaNDL could be an autoimmune disorder, conceptually similar to Guillain-Barré syndrome [7]. Approximately one third of patients with HaNDL have symptoms of a “viral” illness in the preceding 3 weeks. It is possible that such an infection could activate the immune system, which would produce antibodies to neuronalor cranial vessel antigens. This may induce the transient neurologic symptoms throughout a spreading depression-like mechanism and then aseptic vasculitis, which would account for the “vascular” headache and CSF pleocytosis [1].
Conventional brain MRI, as a rule, is normal, and in fact, Gómez-Aranda et al. [7] assume this as a diagnostic criterion. However, there were reports of abnormal findings mostly non-specific in many cases [13, 14] like in our case. In the present case, melanin deposits were detected in the cerebellum with the involvement of dentate nucleus in both sides without any associated cutaneous lesions and the case fulfilled the criteria of HaNDL, so we considered this finding as just non-specific association. Cerebral angiography has been almost invariably normal in cases with HaNDL [7] and can be responsible for triggering an episode of neurologic deficit as reported by Cifelli and Vaithianathar [15].