Familial occurrence of cervical artery dissection--coincidence or sign of familial predisposition?

UNLABELLED: BACKGROUNDAND PURPOSE: The etiology of spontaneous cervical artery dissection (CeAD) is poorly understood in most patients. Mild cervical trauma preceding the dissection event is a common finding, but many CeAD occur spontaneously. It is likely that genetic factors may increase the risk for CeAD. However, familial cases are excedingly rare. Familial clustering of CeAD may be accidental or associated with genetic or environmental risk factors shared between affected relatives. In this explorative study, we aim to show that specific risk factors for familial CeAD exist. METHODS: Age of onset, sex, affected artery and number of recurrent CeAD were documented for familial patients and compared with published findings from patients with sporadic CeAD. Concordance of age, sex and dissected artery within the families was analyzed by correlation analysis and by analysis of variance or Kruskal-Wallis testing. RESULTS: The study sample consisted of 9 new patients with a family history of CeAD enrolled in the Neurology Department of the University of Heidelberg or referred to Heidelberg from other centers. The study sample also included published findings from another 23 patients, in total 32 patients. The mean age of the patients with familial CeAD at their first dissections was 38.4 ± 13.3 years. Twenty (62.5%) patients were female and 12 patients (37.5%) suffered multiple dissections. Four patients (12.5%) presented with recurrent dissections after >1 year. Patients with a familial history of CeAD were younger (p = 0.023) and presented more often with multiple dissections (p = 0.024) and recurrent dissections (p = 0.018). Age at the first event (correlation analysis p = 0.026; analysis of variance p = 0.029) and site of the dissection (correlation analysis p = 0.032; Kruskal-Wallis test p = 0.018) differed between the families, and there was no concordance of gender of affected family members (correlation analysis p = 0.500; Kruskal-Wallis test p = 0.211). CONCLUSIONS: The high prevalence of multiple dissection events and of long-term (>1 year) recurrent dissections in patients with a familial history of CeAD indicates that a specific predisposition for familial CeAD exists. Since age of onset and affected vessel differ between families, the risk profile for familial CeAD is heterogeneous. A large-scale (whole exome) sequencing analysis of 14 patients from 7 of the analyzed families is currently being performed in order to identify causative genetic variants.

Reliability of measuring lesion volumes in transient ischemic attack and minor stroke.

BACKGROUND AND PURPOSE: Lesion volume measurements in disabling ischemic stroke have excellent reliability, but it is not clear whether this is also true for small lesions. We assessed the reliability of measuring baseline and follow-up lesion volumes in transient ischemic attack and minor stroke. METHODS: Patients who presented with a transient ischemic attack or minor stroke (NIHSS < or = 3) who had brain MRI within 24 hours from symptom onset and at 30-day follow-up and had an acute lesion on baseline MRI were included. Using semiautomated software, 4 stroke fellows independently assessed ischemic lesions twice on acute diffusion-weighted imaging and follow-up fluid-attenuated inversion recovery. RESULTS: Eighty patients were included, with a median baseline NIHSS of 1. Mean baseline diffusion-weighted imaging lesion volume was 3.4+/-7.4 mL (87.5% had <5 mL). There was excellent inter-rater/intrarater reliability, with intraclass correlation coefficients of 0.94/0.96 for acute diffusion-weighted imaging, 0.74/0.92 for follow-up fluid-attenuated inversion recovery, and 0.81/0.93 for growth. CONCLUSIONS: We found excellent concordance between and within raters for acute diffusion-weighted imaging and 30-day follow-up fluid-attenuated inversion recovery lesion volume measurements in patients with transient ischemic attack and minor stroke.

Recurrent events in transient ischemic attack and minor stroke: what events are happening and to which patients?

BACKGROUND AND PURPOSE: The risk of a recurrent stroke after transient ischemic attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute treatment options in these patients. We sought to evaluate the type of recurrent events and to identify which subsets of patients are at risk for recurrent events. METHODS: One hundred and eighty patients with TIA or minor stroke were examined within 12 hours and underwent brain MRI within 24 hours. Any neurological deterioration was recorded, and a combination of clinical and MRI factors were used to create a combined event classification. Subgroups of patients analyzed included classical TIA, patients with NIHSS=0, and patients with NIHSS >0 in ED. RESULTS: Overall there were 38 events in 36 patients (20% event rate); 20 were symptomatic and 18 were silent (only evident because of the follow up MRI). 18/20 (90%) symptomatic events were associated with progression of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke distinct from the original event. We found a low risk of recurrent stroke among classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had an intermediate event rate (6.6%) between TIA (classical - 1.1%) and NIHSS >0 (14.4%; chi(2) test for trend, P=0.02). All clinical categories of patient (TIA, stroke, NIHSS=0) accumulated silent lesions on MRI. CONCLUSIONS: Most events were classified as stroke progression or infarct growth rather than a recurrent stroke. A low risk of recurrence was found in patients with classical TIA and those with no neurological deficits on initial assessment.

"Salt and pepper" in the eye and face: a prelude to brainstem ischemia.

PURPOSE: To report the "salt and pepper"(SP) eye pain as a herald symptom of pontine ischemia. DESIGN: Observational case series. METHODS: We reviewed clinical and neuroimaging findings of four patients who presented initially with the sensation of SP in the eyes and then developed paramedian pontine infarcts confirmed by neuroimaging. RESULTS: All of the patients developed other neurologic symptoms or signs, either in association with the sensation of SP in the eyes, from hours to days later. Magnetic resonance imaging (MRI) showed paramedian pontine infarcts in all of the patients and angiography showed basilar artery occlusive disease in three of them. CONCLUSION: Impending pontine ischemia is an important differential diagnosis in patients with acute ocular pain. Prompt neurovascular evaluation and treatment may avoid devastating brainstem infarcts that cause death or long-term disability, particularly in patients with basilar artery occlusive disease.

Primary headaches and painful spontaneous cervical artery dissection.

The relation between primary headaches (PH) and pain related to spontaneous cervical artery dissection (SCAD) is still unclear, as well as the progress of PH after dissection. To investigate this relation, the characteristics of pain related to SCAD and changes in PH patterns after SCAD, we evaluated 54 consecutive patients. Thirty-five (65%) had previous PH. Painful SCAD occurred in 39 (72%). Frontal and parietal localizations were significantly associated with internal carotid artery dissection (p=0.013 and p=0.010, respectively), whereas occipital and nuchal pain, with vertebral artery dissection (p=0.047 and p<0.001, respectively). Previous PH did not influence the presence of pain at SCAD onset. Twenty-six (74%) patients with PH reported improvement in PH pattern after a mean follow-up of 32 months. These results suggest that mechanisms underlying PH do not modulate dissection-related pain. Disruption of perivascular afferents may be involved in improvement of PH patterns after SCAD.