Dental procedure induced cerebellar haemorrhage with visual tilt and unsuspected CADASIL

Abstract

A man in his late 60s had vertigo and vision tilt following a dental procedure. A cerebellar haemorrhage and cerebral microbleeds (CMBs) were diagnosed on imaging. Subsequent testing revealed CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The role of the dental procedure as a trigger for intracerebral haemorrhage (ICH) is discussed. The incidence of CMBs and ICH in CADASIL is discussed. A summary of the causes and pathology associated with visual tilt is documented.

Background

Intracerebral haemorrhage (ICH) is the second most common pathological imaging finding after ischaemia in patients with stroke syndrome.¹ There are multiple causes of ICH including hypertension, reversible cerebral vasoconstrictive syndrome, vascular malformations, amyloid angiopathy, metastatic or primary cerebral cancers, drug use, coagulopathy and trauma. Unusual cases of ICH have been described in the setting of dental pain, cold weather, surgery for trigeminal neuralgia and delayed cerebral trauma.² Presumably, the underlying pathophysiology is an acute elevation in blood pressure, since most cases had no known underlying cause.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a monogenic autosomal dominant hereditary cerebral small blood vessel disease caused by a mutation in NOTCH3. It causes lacunar infarction, white matter disease (leukoencephalopathy), microbleeds and dementia.

Our case discusses visual tilt, the role of dental procedures as a trigger for intracranial haemorrhage and the diagnosis of CADASIL.

Case presentation

A man in his late 60s presented to the emergency department after having two teeth extracted under local anaesthetic. Thirty minutes after the procedure, he developed sudden-onset nausea, vomiting, dizziness and visual changes described as rotation of objects 90° in an anticlockwise direction. His medical history was only significant for suspected Parkinson’s disease by his general practitioner after noticing a shuffling gait. A non-contrast CT of the brain 6 weeks prior to this event showed no previous lacunar infarctions but significant bilateral periventricular white matter disease. He did not have any history of hypertension and did not smoke or drink alcohol. Importantly, there was no personal or family history of cerebrovascular disease, cognitive decline or migraines.

On examination, his blood pressure was 170/75 mm Hg, while the rest of vital signs were within the normal ranges. There was left-sided nystagmus at extreme lateral gaze. His power was assessed as 5/5 in the proximal and distal muscles of the arms and legs bilaterally. His gait was unsteady, with the patient falling to the right side. There was incoordination of the left upper limb. However, sensory examination and the remainder of his physical examination, including his speech, were normal. Fundal examination did not elicit any evidence of hypertensive retinopathy.

Investigations

The white cell count was 13.8 (reference range, 4–11×10⁹/L), with a normal differential count. The remainder of the complete blood count was normal, as was his liver function, coagulation profile, cholesterol panel, kidney function, electrolyte levels, vitamin B₁₂ and plasma-free metanephrines. Urgent CT of the brain showed a left cerebellar haemorrhage adjacent to the fourth ventricle extending to the ventricle’s wall (figure 1). Further MRI of the brain showed a focal ovoid haematoma (24×25 mm transaxial) in the region of the left dentate nucleus with extensive punctate haemosiderin foci, predominantly involving the thalami, but also the pons and contralateral cerebellum as well as a few more peripherally located foci within the frontal, parietal and temporal cortices. Severe confluent periventricular and mild pontine leukoencephalopathy were also noted, which likely represent small vessel ischaemic changes (refer to figures 2–4).

Figure 1.

Axial and coronal CT of the brain showing an 11 mm×21 mm sized high attenuated area at the left cerebellar hemisphere adjacent to the fourth ventricle (arrows).

Figure 2.

MRI of the brain showing a focal ovoid haematoma in the region of the left dentate nucleus (arrows).

Figure 3.

MRI T2 Flair axial and coronal showing Fazekas grade 3 white matter lesions. (a) Symmetrical periventricular white matter hyper intensities, (b) external capsule and (c) anterior temporal lobe white matter hyper intensities.

Figure 4.

MRI showing numerous centrally located microbleed (arrows). It is estimated that there are about 10 microbleeds in the infratentorial and 30 microbleeds in supratentorial regions.

Genetic analyses were performed with the direct DNA sequence analysis of exons 2–8, 11, 18, 19, 22 and 23 of the NOTCH3 gene which identified a heterozygous C to T nucleotide substitution at position 1630 in exon 11. This resulted in arginine‐to‐cysteine substitution (p.Arg544Cys), consistent with the diagnosis of CADASIL.

Outcome and follow-up

At 3 months follow-up, the patient had reported improvement in his symptoms. He denied having any further visual changes and stated that his unsteadiness had improved significantly. His blood pressure was well controlled with amlodipine. He was commenced on long-term aspirin, given his risk of further ischaemic strokes.

Discussion

We present here a rare case of a dental procedure as a cause of ICH in the context of a patient with CADASIL, cerebral microbleeds (CMBs) and hypertension. This is only the fourth case in the literature involving a dental procedure associated with an ICH and the first in a patient with CADASIL.

A fatal case of a normotensive 52-year-old woman with a dental abscess and severe pain has been previously reported by Barbas et al.³ She had headaches and vomited prior to any anaesthetic and subsequently became comatose. A CT scan showed a massive cerebral haemorrhage involving the left temporal, parietal and basal ganglia. Angiography was normal, and the autopsy found no vascular cause. The role of acute hypertension was discussed as a probable cause, as this has been seen with drug use (cocaine, amphetamines) and cold weather. Trigeminal nerve stimulation also increases cerebral blood flow and can elevate blood pressure.⁴ Fatal intracerebral hemorrhages (ICHs) have been reported as a consequence of radiofrequency trigeminal lesioning. Additionally, three cases of ICH were described in patients following exposure to extremely low temperatures.¹ Recently, a patient with a history of hypertension had an ICH after an ‘ice bucket challenge’ for motor neuron disease.⁵ Two middle-aged females with a history of hypertension also suffered fatal ICHs after dental treatment.⁶

CADASIL and Intracranial haemorrhage

Compared with lacunar ischaemic events, ICH was previously considered rare in CADASIL. Recently, there has been increasing literature on ICH in CADASIL patients. Liao et al ⁷ investigated 127 Taiwanese genetically proven CADASIL patients and found that 37 (29%) had ICH, 15 symptomatic and 22 asymptomatic. Thalamic and lobar (frontal, temporal) haemorrhages were the most common and lobar ICHs were often silent. Risk factors included hypertension, the burden of CMB (>10 CMBs and brainstem CMBs) and higher small vessel disease score. Age, sex, Notch mutation and APOE genotype were similar to the control cohort of non-ICH CADASIL patients. Asian ethnicity doubles the risk of ICH generally and specifically for CADASIL. The prevalence of ICH in Caucasian CADASIL patients is 0.5%–2%. The paper suggests tighter blood pressure control aiming for <120/80 and cautious use of antiplatelets in patients with a high small vessel score and CMBs>10. A French/German study of 369 patients revealed that CMB was an independent risk factor for ischaemic events (HR 1.87).⁸ CMBs are found in 34%–75% of patients with CADASIL.⁹ The location of the CMB’s in 43 of the 125 (34%) patients was supratentorial lobar location in 22%, deep subcortical 34% and 18% infratentorial.¹⁰ As the finding of multiple CMBs can cause the misdiagnosis of cerebral amyloid angiopathy (CAA), a study looked at the spatial distribution of CMBs in CADASIL and found higher incidence CMBs in the hippocampus/amygdala, insula, and temporal lobes and lower in parietal lobes compared with CAA. CMBs in the thalamus, basal ganglia and pons were associated with ICH, but cerebellar haemorrhage is distinctly uncommon.^{11 12} Patients with CADASIL typically develop stroke-like symptoms between the ages of 20–40 years and have dementia by 60 years of age. In our patient, the MRI findings were incidental and suggestive of CADASIL. Carriers of the mutation may be asymptomatic, especially if there are no lacunar infarctions.¹³

Visual inversion and tilting

The experience of visual tilting is called ‘room tilt illusion’ (RTI). It can be associated with vertebrobasilar insufficiency, lateral medullary infarction, migraine, vestibular epilepsy and labyrinthine disease.^14–16 The visual fields of both eyes are turned either clockwise or counter-clockwise by 90°–180°. The vision remains clear but is accompanied by subjective dizziness. The illusion is often brief and persists over a few days. The explanation is probably due to mismatching visual to vestibular information with regard to spatial orientation. The otoliths and their connections are most likely at fault. The illusion can be reproduced experimentally by a sudden change in the direction of body rotation, the ‘oculogravic illusion’.

Two cases of RTI due to cerebellar lesions were reported by Mossman and Halmagyi,¹⁷ with one patient having a caudal cerebellar haemorrhage and the other patient an infarct in the territory of the posterior inferior cerebellar artery.

The cerebellar nodulus receives a large input from the otoliths. Infarction in the territory of the medial branch of the posterior inferior cerebellar artery (PICA) affects the nodulus and vermis. Otoliths are important for gravity orientation and head position and rotation. MRI of our patient demonstrates the close relation of the haemorrhage to the nodulus (refer to figure 2).

In summary, we describe a patient with unsuspected CADASIL who presented with a cerebellar haemorrhage following dental manipulation and experienced transient RTI.

Learning points.

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) typically causes stroke like syndromes from lacunar infarction.

• MRI findings of extensive white matter disease with lacunar infarcts and cerebral microbleeds (CMBs) is an indication for CADASIL gene testing.

• CMBs increase the risk of stroke and intracerebral haemorrhage (ICH).

• Extreme cold and dental procedures can trigger ICH.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).