Sir,

Headache, neurologic deficits, and cerebrospinal fluid lymphocytosis (HaNDL) syndrome was first described as a migrainous syndrome with cerebrospinal fluid pleocytosis in 1981.1 Recently, the ophthalmologic involvements in HaNDL have been emphasized.2 We present ophthalmologic manifestations in an unusual case of HaNDL syndrome with nonspecific frontal lesions and hyperthyroidism.

Case report

A 39-year-old woman without personal or family history of migraine experienced 2 weeks of severe retrobulbar pain, headache and vomiting with no preceding viral illness. Her visual acuity and eye movement were normal. She had lid retraction in the right eye, bilateral papilloedema and bilateral tonic pupil. Goldmann perimetry showed bilateral enlargement of the blind spots. Additionally, the patient was diagnosed with hyperthyroidism 4 months previously. She was admitted to our hospital and a general neurological examination was unremarkable. She was not obese and she had no fever or any meningeal signs. All routine blood tests and haematochemistry were normal. No abnormal titres were found in the serum antibodies for any viruses. Several autoantibodies were negative (s-IL2 receptor, dsDNA, RNP, SS-A/B, c-ANCA, and p-ANCA).

Lumbar puncture revealed an opening pressure of 160 mmH2O and 51.7 cells/mm3 (lymphocytic predominance). Protein, glucose, and IgG in the cerebrospinal fluid were within normal limits and the oligoclonal band was negative.

Free T3 and T4 were within normal limits on admission, but the serum level of thyroid-stimulating hormone increased over time. While the antibodies for thyroid-stimulating hormone receptor and thyroglobulin were negative, the thyroid peroxidase antibody was positive. She was diagnosed with chronic thyroiditis (Hashimoto's disease) with rapid exacerbation.

T2-weighted magnetic resonance imaging (MRI) revealed small nonspecific areas of hyperintensity in the bilateral frontal lobe (Figure 1). She manifested horizontal gaze-evoked nystagmus, tinnitus and dysaesthesia of her bilateral fingers. These symptoms were temporary and self-limited. After 3 weeks , a repeat lumber puncture revealed 13.3 cells/mm3. The papilloedema resolved following a 1-month course of acetazolamide.

Figure 1
figure 1

MRI showing multiple lesions (arrows).

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Comment

The papilloedema, headache, cerebrospinal fluid lymphocytosis and temporary symptoms of horizontal gaze-evoked nystagmus, tinnitus, and dysaesthesia in the present case are highly suggestive of HaNDL. Berg et al3 termed this syndrome HaNDL and the diagnostic criteria proposed included severe headache, temporary neurologic deficit, cerebrospinal fluid lymphocytosis and being self-limited. The present case fulfilled the diagnostic criteria and the disorder was differentiated from other migrainous syndromes. The differential diagnoses for migrainous diseases are listed in the Table 1. Barkana et al4 has reported six cases with intracranial hypertension and unexplained cerebrospinal fluid pleocytosis. If these cases had temporary neurologic deficits, they also could be HaNDL. Although HaNDL is an uncommon disease, ophthalmologists must include HaNDL in any differential diagnosis used to assess patients with papilloedema and temporary neuro-ophthalmological signs.

Table 1 Differential diagnoses for migrainous diseases
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The neuroimaging abnormality we noted was similar to that mentioned previously in an advanced form of HaNDL.3, 5 The lid retraction in our case may be relevant to the hyperthyroidism. Tonic pupil may be due to a variety of causes including inflammation, vasculitis, or ischaemic processes that affect the ciliary ganglion in patients with autoimmune diseases.6, 7, 8 The association of tonic pupil with hyperthyroidism and myasthenia gravis as part of an autoimmune disease has been previously reported.9 In this case, the patient was associated with Hashimoto’s disease, which is an autoimmune disease. Although the precise aetiology of the association remains obscure, the tonic pupils in this case could be related to an autoimmune disease.

Thus far, no clear causal link has been established between Hashimoto’s disease and cerebrospinal fluid lymphocytosis, although hyperthyroidism is known to cause increases in intracranial pressure.10 The aetiology of HaNDL is unknown but an inflammation such as an allergic response after an infection or an autoimmune disease is more likely rather than an infection because of the noninfectious profile that is seen on cerebrospinal fluid analysis, the lack of fever, and a normal serum complete blood count. Autoimmune disorders might be one of causative factors of HaNDL. Further examples are required in order to clarify an aetiologic relationship between thyroid dysfunctions or autoimmune conditions and HaNDL.