Optic ataxia in a patient with HaNDL syndrome

Abstract

We present a woman in her 40s who arrived at the emergency room with hypertension and optic ataxia. Her medical history is only relevant for obesity. Her lumbar puncture revealed high intracranial pressure and lymphocytic pleocytosis, and her neuroimaging tests, including angiography and venography, were normal. The patient improved after a cerebrospinal fluid drainage with a lumbar puncture, and her clinical manifestations resolved in parallel to the lymphocytic pleocytosis.

The patient was diagnosed with a syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis and fully recovered 21 days after her discharge.

Background

Optic ataxia is a clinical finding of damage to the parieto-occipital junction, so it is a visuomotor disorder not attributable to primary visual, proprioceptive, cerebellar or cognitive deficits. Optic ataxia is named as such because it consists of a visual (optical) guidance difficulty (ataxia) towards objects. People suffering from optic ataxia can usually reach and accurately grasp targets that are directly fixed, but the ability to quickly correct the trajectory is severely impaired. This impairment makes it difficult to interact with their environment.^{1 2} Also, reaching with the contralateral hand is often inaccurate, even for fixed targets. It is a part of the Balint syndrome, including ocular apraxia and spatial disorder of attention, as described by Rudolph Balint in 1909.³

A headache can be a disabling pain that may be the reason for a visit to the emergency room (ER). When a patient arrives at the ER with headache as the main report, the diagnostic approach begins with the classification of the headache disorder: only about 18% of patients with a headache have a secondary headache disorder. However, these conditions can be life-threatening, so the presence of ‘red flags’ with the SNNOOP10 (systemic, neoplasm, neurologic deficit, onset, old, onset recent, positional, precipitated, papilledema, progressive, pregnancy or puerperium, painful eye, posttraumatic, pathology, painkiller overuse) list can guide the diagnostic approach to determine who needs further evaluation added to a proper neurological examination.⁴

The association of focal deficits and headache in a patient with high blood pressure (BP) raised the suspicion of a vascular disorder as the most probable aetiology of the patient’s headache. Therefore, it required a neuroimaging study with MRI as the preferred modality.

In an obese patient with a new-onset headache, cerebrospinal fluid (CSF) analysis can reveal critical findings such as the presence of high intracranial pressure.

Case presentation

A woman in her 40s with a history of obesity was admitted to the ER. She had ‘the worst headache of her life’. She started with a mild frontal and pulsatile headache, gradually worsening over 3 days and did not respond to analgesics. Before arriving at the ER, she saw a general practitioner who found her BP to be 200/100 mm Hg, so he prescribed amlodipine, telmisartan and ibuprofen as treatment. Nevertheless, the treatment did not relieve her symptoms, and on the third day of the headache, she noted blurred vision and decided to go to the ER.

During a physical examination, her BP was 160/80 mm Hg and the rest of her vital signs were average. She was alert, a semantic aphasia was noted and the rest of the mental examination showed nothing of relevance. Her visual acuity was 60/20 bilaterally with no field-camp defects and bilateral papilloedema. Optic ataxia manifested with an inability to reach things by visual tracking but improved on command. The patient followed the noise of the object that she needed to reach. The rest of the cranial nerves were normal. Motor examination was relevant only for generalised hyper-reflexia. Dysdiadochokinesia and dysarthria were absent (which would be present if it were cerebellar ataxia). There was no nuchal rigidity; and in the rest of the neurological examination, nothing of significance was found.

Investigations

We took a diagnostic serum test at the ER, which included complete blood count, creatinine, urea, glucose and electrolytes, and all resulted average.

After a normal CT scan, we performed a lumbar puncture (LP) at admission, with an opening pressure of 61 mmH₂O. The CSF was clear and had a cell count of 387 cells/mm³: 95% lymphocytes, 5% polymorphonuclear, serum/CSF glucose ratio was 0.68 and protein was 37 mg/dL. The India ink test, Gram stain and PCR for Mycobacterium tuberculosis were all negative. A CSF PCR panel for meningitis/encephalitis was carried out; this study included herpes simplex virus 1, 2, 6, Epstein-Barr virus, cytomegalovirus, enterovirus, Streptococcus pneumoniae, type B Haemophilus influenzae and Neisseria meningitides; and all of them were negative.

A second LP done 4 days after admission revealed an opening pressure of 28 mmH₂O and a clear CSF. The analysis had a cell count of 120 cells/mm³: 98% lymphocytes and 2% polymorphonuclear and an average serum/CSF glucose ratio.

Differential diagnosis

Posterior reversible leucoencephalopathy syndrome

Posterior reversible leucoencephalopathy syndrome (PRES) is a neurological disorder of vascular origin because of an endothelial dysfunction originated from endogenous or exogenous factors (sepsis, pre-eclampsia) or cerebral hyperperfusion due to an abrupt increase in BP resulting in vasogenic oedema. PRES is a condition that frequently presents with an encephalopathy, a headache and visual disturbances in patients with a history of hypertension or pre-eclampsia.⁵ However, it can be accompanied by other clinical findings such as seizures, status epilepticus and focal deficits. Optic ataxia, with the full features of Balint syndrome, has been reported in a patient with PRES due to hypertension related to lupus nephritis.⁶

PRES is a clinical-radiological diagnosis that requires demonstrating vasogenic oedema in a CT scan or MRI and reversing the clinical and radiological findings. However, no evidence of a vasogenic oedema was found in the MRI (figures 1–3) of our patient; thus, we excluded this possible diagnosis.

Figure 1.

Normal axial T2-weighted fluid-attenuated inversion recovery at the basal ganglia with no evidence of lesions.

Figure 2.

Normal axial T1 post-gadolinium with no meningeal enhancement.

Figure 3.

Normal axial T2.

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS), previously known as Call-Fleming syndrome, central nervous system (CNS) pseudovasculitis or others, is a clinical condition manifested by thunderclap headache with other focal deficits and evidence of a diffuse constriction of the CNS arteries. This syndrome is characterised by the reversion of the clinical manifestations and cerebral vasoconstriction in the following 3 months of the presentation.

In patients with RCVS, neuroimaging can demonstrate subarachnoid haemorrhage located on the convexity and can also show an ischaemic stroke or parenchymal haemorrhages. Although the diagnosis of this condition requires imaging of the brain vascularisation, direct or indirect cerebral angiography is the study of choice for the diagnosis. The cerebral angiography can show vasoconstriction of any cerebral arteries.^{7 8}

It is known that the sensitivity of indirect angiography can be as low as 70%, especially when it is done in the first week after the beginning of symptoms. We excluded RCVS as the cause of this patient’s presentation due to the elevated cell count and intracranial pressure in the LP. CSF findings in RCVS need to be unaltered or near normal, with a cell count below 10 cells/mm³. One case has been reported with a series elevation of 29 cells/mm³,⁹ more than 10 times lower than what we found in our patient.

Cerebral venous thrombosis

Nowadays, with the vaccines against SARS-CoV-2, there have been increasing reports of thrombotic events, including cerebral venous thrombosis (CVT). The brain has a venous drainage system of a series of large sinuses that receive blood from deep and cortical veins. The venous structures in the brain include the superior sagittal sinus, the confluence of the sinuses, the transverse sinus, the sigmoid and straight sinus, and the Trolard and Labbé veins. However, the complete review of the anatomy of the brain’s venous drainage is beyond the purpose of this paper.¹⁰

CVT clinically manifests with a headache: in one study of 624 patients with CVT, the most common presentation was a subacute headache (55%).¹¹ The pattern of the headache in a study of 47 patients had a holocranial localisation in 36%, followed by frontal in 27%; and the presence of throbbing pain was described in 44.7% of the patients.¹²

CVT is a diagnosis that leads to the suspicion of a hypercoagulable state, which can be puerperium/pregnancy, dehydration, cancer related, and recently, the entities related to the platelet-activating antibodies to platelet factor 4. There are three conditions that are essential to recognise: vaccine-induced immune thrombotic thrombocytopenia, heparin-induced thrombocytopenia (HIT) and autoimmune HIT. Neuroimaging demonstrates the presence of venous infarcts, which usually have a haemorrhagic transformation near the site of thrombosis, and some signs such as the ‘empty delta sign’ on a CT scan or MRI.¹³

In our patient, the headache with neurological deficits and the high intracranial pressure raised suspicion for the CVT, but the MRI venography had no significant findings. Thus, we excluded this diagnosis because of the lack of imaging evidence of CVT (figures 4 and 5).

Figure 4.

Venography of the patient without evidence of thrombosis of the brain sinuses: (A) coronal view and (B) sagittal view.

Figure 5.

Magnetic resonance angiography shows normal intracranial vessels.

Aseptic meningitis

Aseptic meningitis is a group of conditions that shares meningeal inflammation that could be of non-infectious origin, for example, a drug-induced meningitis or systemic diseases with meningeal involvement and malignant processes, and infectious causes, which are mainly virus-related infections. However, in almost two-thirds of cases, there is no identifiable aetiology.¹⁴

Clinical manifestations depend on the aetiology, and headache is one of the most frequently identified manifestations. This has been documented in observational studies where it has been found that in the totality of the patients diagnosed with meningitis of infectious origin, a headache manifests in almost 71.4% of non-infectious aseptic meningitis of autoimmune origin. In nearly one-third of the cases, headache is related to other symptoms less frequently reported, such as photophobia, fever, nausea, vomiting, nuchal rigidity and encephalitis-like courses.¹⁵

In infectious causes, on CSF analysis, pleocytosis is typically found, in which there is a lymphocytic predominance in 24%–100% of the cases, with the possibility of neutrophilia on an initial phase that turns into a lymphocytosis within 24–48 hours. There is also a moderate elevation of the CSF proteins and glucose ranging from average to low levels.¹⁶

Our patient was investigated for the most common causes of infectious diseases causing meningitis and encephalitis, including M. tuberculosis. The lack of elevation on CSF proteins and evidence of systemic inflammation did not support aseptic meningitis of autoimmune origin.

Idiopathic intracranial hypertension

Due to the patient’s clinical characteristics (female, overweight, intense headache and papilloedema and elevated intracranial pressure), idiopathic intracranial hypertension (IIH) played an essential role as a differential diagnosis, especially in a patient with a normal MRI.

Diagnostic criteria for IIH,¹⁷ which our patient did not have, included the sixth nerve palsy and MRI findings that support the diagnosis like empty sella, flattening of the posterior aspect of the ocular globe, enlargement of the periodic arachnoid space with or without tortuous optic nerve and transverse venous sinus stenosis.^{18 19}

Perhaps the most important clue was the altered CSF composition, which ruled out IIH as a diagnosis.²⁰

Syndrome of transient headache and neurological deficits with CSF lymphocytosis

Syndrome of transient headache and neurological deficits with CSF lymphocytosis (HaNDL) is a rare cause of secondary headache, according to the International Classification of Headache Disorders third edition (ICHD-3). It is characterised by migraine-like episodes lasting for hours and is accompanied by CSF lymphocytic pleocytosis and focal neurological deficits. Usually, the focal deficits have been described as dysphasia, hemiparaesthesia or hemiparesis lasting for more than 4 hours.²¹

Clinical manifestations can be broad. Babi et al reported two cases of HaNDL that presented to the ER with focal deficits and were found to have this condition, improving after discharge.²²

The diagnosis of HaNDL is based on the diagnostic criteria of the ICHD-3 (episodes of migraine-type headache, accompanied or preceded by the appearance of at least one of the following transient neurological deficits lasting less than 4 hours: (a) hemiparaesthesia, (b) dysphasia, (c) hemiparesis). This syndrome is associated with a CSF lymphocytic pleocytosis (>15 white blood cells per µL), with negative aetiological studies. One or both of the following demonstrate causality: (1) headache and transient neurological deficits have developed or significantly worsened in association with, or have led to the discovery of, CSF lymphocytic pleocytosis; (2) headache and transient neurological deficits have significantly improved in parallel to the improvement of CSF lymphocytic pleocytosis, with the condition of having no better diagnosis to explain it (ICHD-3).²¹

Treatment

We drained 30 mL of CSF in the first LP, after which she noted an improvement in her headache. We also treated her headache with paracetamol and acetazolamide.

Outcome and follow-up

The patient was discharged 6 days after her admission to treat her headache, her vision was 25/20 bilateral and the optic ataxia was resolved. We followed up with the patient and saw her at our clinic 21 days after the beginning of her symptoms. She denied having headaches and other symptoms since her discharge, and her BP was controlled.

Discussion

Optic ataxia is a focal deficit that arises from damage to the posterior parietal cortex, an area in which there are complex connections within the parietal lobule and other brain areas. From this principle, we know that optic ataxia results from a disruption in these connections that comprise the parietal reach region. Balint syndrome arises from bilateral damage to these parietal areas. Still, there is evidence from some case reports and studies that suggest that it can be found in patients with unilateral lesions.

Optic ataxia is characterised by a disruption of visuomotor processing, visual orientation and online visuomotor control. The areas involved in this complex process include the parietal reach region, lateral intraparietal area, the anterior intraparietal area and dorsal Brodmann’s area 5, which when damaged can result in an optic ataxia, eye movement deficits and extinction, and grasp deficits and state estimation deficits, respectively.²³

HaNDL syndrome, previously called pseudomigraine with lymphocytic pleocytosis,²² can be a difficult diagnosis, especially in patients who present to the ER with red flags. This is to highlight that this is an exclusion diagnosis, and it is imperative for the neurologist to discard life-threatening conditions. First, in a patient with focal deficits and high BP, we must ask for a neuroimaging study because of the suspicion of a stroke. CVT usually has a subacute course, but the headache is the most common clinical manifestation, and neuroimaging can be abnormal in almost 82% of the patients.¹⁰ For visual abnormalities related to headache, PRES and RCVS are conditions that come to mind immediately because of the high prevalence of the compromise to the posterior brain regions.

For the pathophysiology of HaNDL syndrome, there are some hypotheses. It has been proposed that a viral infection leads to the lymphocytic infiltration of meninges and is supported by the prodromal viral symptoms presented before the headache. Other hypotheses suggest that HaNDL syndrome could be a complicated migraine with meningeal inflammation due to the vascular changes associated with the migraine and is supported by some changes in transcranial Doppler that exhibit vasomotor features like migraine.²⁴

The clinical manifestations described here are the presence of migraine-like episodes. The focal deficits required in the ICHD-3 criteria are dysphasia, hemiparaesthesia and hemiparesis. However, there are case reports of other clinical manifestations, including complete ophthalmoplegia²⁵ and an acute confusional state.²⁶ Visual symptoms are not uncommon. Due to the association of HaNDL and migraine, patients can present to the ER with visual abnormalities accompanied by other focal features such as tinnitus and hemiparaesthesia, which resolve in parallel with the lymphocytic pleocytosis, thus, fulfilling the ICHD-3 criteria.²⁷

Management of HaNDL, because of its self-limited course, is limited to pain relief. Still, there is some information about the efficacy of oral corticosteroids and, in papilloedema cases, of acetazolamide.²⁸

For our patient, as previously discussed on the Differential diagnosis section, we first discarded the most common aetiologies that could explain her clinical manifestations. After we discarded the first conditions, we considered HaNDL as a diagnostic possibility. We did not find other case reports of HaNDL syndrome associated with optic ataxia, which is why we present this clinical finding with the follow-up of this patient.

Patient’s perspective.

I feel relieved after the symptoms have resolved entirely, although I am concerned about the probability of having a new event like this one in the future.

Learning points.

• Patients with headaches and red flags at the emergency room (ER) must have a diagnostic work-up for discarding life-threatening causes.

• In a patient with new-onset headaches, neurological findings and high blood pressure, we should consider vascular causes.

• Aseptic meningitis is a cause to consider in secondary headaches in patients with red flags.

• Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis can cause headaches and optic ataxia and should be a clinical differential diagnosis of migraine in an ER approach.

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Patient consent for publication

Obtained.